Phenotypic changes in artemisinin-resistant plasmodium falciparum lines in vitro: evidence for decreased sensitivity to dormancy and growth inhibition

The appearance of Plasmodium falciparum parasites with decreased in vivo sensitivity but no measurable in vitro resistance to artemisinin has raised the urgent need to characterize the artemisinin resistance phenotype. Changes in the temporary growth arrest (dormancy) profile of parasites may be one aspect of this phenotype. In this study, we investigated the link between dormancy and resistance, using artelinic acid (AL)-resistant parasites. Our results demonstrate that the AL resistance phenotype has (i) decreased sensitivity of mature-stage parasites, (ii) decreased sensitivity of the ring stage to the induction of dormancy, and (iii) a faster recovery from dormancy.

Fabrication and in vitro characterisation of bioactive glass composite scaffolds for bone regeneration

Here we fabricate and characterise bioactive composite scaffolds for bone tissue engineering applications. 45S5 Bioglass® (45S5) or strontium-substituted bioactive glass (SrBG) were incorporated into polycaprolactone (PCL) and fabricated into 3D bioactive composite scaffolds utilising additive manufacturing technology. We show that composite scaffolds (PCL/45S5 and PCL/SrBG) can be reproducibly manufactured with a scaffold morphology highly resembling that of PCL scaffolds. Additionally, micro-CT analysis reveals BG particles were homogeneously distributed throughout the scaffolds. Mechanical data suggested that PCL/45S5 and PCL/SrBG composite scaffolds have higher compressive Young’s modulus compared to PCL scaffolds at similar porosity (~75%). After 1 day in accelerated degradation conditions using 5M NaOH, PCL/SrBG, PCL/45S5 and PCL lost 48.6 ±3.8%, 12.1 ±1% and 1.6 ±1% of its original mass, respectively. In vitro studies were conducted using MC3T3 cells under normal and osteogenic conditions. All scaffolds were shown to be non-cytotoxic, and supported cell attachment and proliferation. Our results also indicate that the inclusion of bioactive glass (BG) promotes precipitation of calcium phosphate on the scaffold surfaces which leads to earlier cell differentiation and matrix mineralisation when compared to PCL scaffolds. However, as indicated by ALP activity, no significant difference in osteoblast differentiation was found between PCL/45S5 and PCL/SrBG scaffolds. These results suggest that PCL/45S5 and PCL/SrBG composite scaffold shows potential as a next generation bone scaffold.

Culture in global business transformation projects : the discovery of a grounded theory

Presently organisations engage in what is termed as Global Business Transformation Projects [GBTPs], for consolidating, innovating, transforming and restructuring their processes and business strategies while undergoing fundamental change. Culture plays an important role in global business transformation projects as these involve people of different cultural backgrounds and span across countries, industries and disciplinary boundaries. Nevertheless, there is scant empirical research on how culture is conceptualised beyond national and organisational cultures but also on how culture is to be taken into account and dealt with within global business transformation projects. This research is situated in a business context and discovers a theory that aids in describing and dealing with culture. It draws on the lived experiences of thirty-two senior management practitioners, reporting on more than sixty-one global business transformation projects in which they were actively involved. The research method used is a qualitative and interpretive one and applies a grounded theory approach, with rich data generated through interviews. In addition, vignettes were developed to illustrate the derived theoretical models. The findings from this study contribute to knowledge in multiple ways. First, it provides a holistic account of global business transformation projects that describe the construct of culture by the elements of culture types, cultural differences and cultural diversity. A typology of culture types has been developed which enlarges the view of culture beyond national and organisational culture including an industry culture, professional service firm culture and 'theme' culture. The amalgamation of the culture types instantiated in a global business transformation project compromises its project culture. Second, the empirically grounded process for managing culture in global business transformation projects integrates the stages of recognition, understanding and management as well as the enablement providing a roadmap for dealing with culture in global business transformation projects. Third, this study identified contextual variables to global business transformation projects, which provide the means of describing the environment global business transformation projects are situated, influence the construct of culture and inform the process for managing culture. Fourth, the contribution to the research method is the positioning of interview research as a strategy for data generation and the detailed documentation applying grounded theory to discover theory.

In vitro biocompatibility of different polyester membranes

Nowadays, synthetic biodegradable polymers, such as aliphatic polyesters, are largely used in tissue engineering. They provide several advantages compared to natural materials which use is limited by immunocompatibility, graft availability, etc. In this work, poly(L-lactic) acid (PLLA), poly(DL-lactic) acid (PDLA), poly-epsilon-caprolactone (PCL), poly(L-lactic)-co-caprolactone (molar ratio 70/30) (PLCL) were selected because of their common use in tissue engineering. The membranes were elaborated by solvent casting. Membrane morphology was investigated by atomic force microscopy. The membranes were seeded with human fibroblasts from cell line CRL 2703 in order to evaluate the biocompatibility by the Alamar blue test. The roughness of the membranes ranged from 4 nm for PDLA to 120 nm and they presented very smooth surface except for PCL which beside a macroscopic structure due to its hydrophobicity. Human fibroblasts proliferated over 28 days on the membranes proving the non-in vitro toxicity of the materials and of the processing method. A further step will be the fabrication of three-dimensional scaffold for tissue engineering and the treatment of the scaffolds to augment cell adhesion.

The effect of polystyrene sodium sulfonate grafting on polyethylene terephthalate artificial ligaments on in vitro mineralisation and in vivo bone tissue integration

This study investigates the impact of polystyrene sodium sulfonate (PolyNaSS) grafting onto the osseo-integration of a polyethylene terephthalate artificial ligament (Ligament Advanced Reinforcement System, LARS™) used for Anterior Cruciate Ligament (ACL). The performance of grafted and non-grafted ligaments was assessed in vitro by culturing human osteoblasts under osteogenic induction and this demonstrated that the surface modification was capable of up-regulating the secretion of ALP and induced higher level of mineralisation as measured 6 weeks post-seeding by Micro-Computed Tomography. Grafted and non-grafted LARS™ were subsequently implanted in an ovine model for ACL reconstruction and the ligament-to-bone interface was evaluated by histology and biomechanical testings 3 and 12 months post-implantation. The grafted ligaments exhibited more frequent direct ligament-to-bone contact and bone formation in the core of the ligament at the later time point than the non-grafted specimens, the grafting also significantly reduced the fibrous encapsulation of the ligament 12 months post-implantation. However, this improved osseo-integration was not translated into a significant increase in the biomechanical pull-out loads. These results provide evidences that PolyNaSS grafting improved the osseo-integration of the artificial ligament within the bone tunnels. This might positively influence the outcome of the surgical reconstructions, as higher ligament stability is believed to limit micro-movement and therefore permits earlier and enhanced healing.

A poly(lactic-co-glycolic acid) knitted scaffold for tendon tissue engineering: an in vitro and in vivo study

We have designed a composite scaffold for potential use in tendon or ligament tissue engineering. The composite scaffold was made of a cellularized alginate gel that encapsulated a knitted structure. Our hypothesis was that the alginate would act as a cell carrier and deliver cells to the injury site while the knitted structure would provide mechanical strength to the composite construct. The mechanical behaviour and the degradation profile of the poly(lactic-co-glycolic acid) knitted scaffolds were evaluated. We found that our scaffolds had an elastic modulus of 750 MPa and that they lost their physical integrity within 7 weeks of in vitro incubation. Autologous rabbit mesenchymal stem cell seeded composite scaffolds were implanted in a 1-cm-long defect created in the rabbit tendon, and the biomechanical properties and the morphology of the regenerated tissues were evaluated after 13 weeks. The regenerated tendons presented higher normalized elastic modulus of (60%) when compared with naturally healed tendons (40%). The histological study showed a higher cell density and vascularization in the regenerated tendons.

Research capacity and culture in podiatry : early observations within Queensland Health

Background Research is a major driver of health care improvement and evidence-based practice is becoming the foundation of health care delivery. For health professions to develop within emerging models of health care delivery, it would seem imperative to develop and monitor the research capacity and evidence-based literacy of the health care workforce. This observational paper aims to report the research capacity levels of statewide populations of public-sector podiatrists at two different time points twelve-months apart. Methods The Research Capacity & Culture (RCC) survey was electronically distributed to all Queensland Health (Australia) employed podiatrists in January 2011 (n = 58) and January 2012 (n = 60). The RCC is a validated tool designed to measure indicators of research skill in health professionals. Participants rate skill levels against each individual, team and organisation statement on a 10-point scale (one = lowest, ten = highest). Chi-squared and Mann Whitney U tests were used to determine any differences between the results of the two survey samples. A minimum significance of p < 0.05 was used throughout. Results Thirty-seven (64%) podiatrists responded to the 2011 survey and 33 (55%) the 2012 survey. The 2011 survey respondents reported low skill levels (Median < 4) on most aspects of individual research aspects, except for their ability to locate and critically review research literature (Median > 6). Whereas, most reported their organisation’s skills to perform and support research at much higher levels (Median > 6). The 2012 survey respondents reported significantly higher skill ratings compared to the 2011 survey in individuals’ ability to secure research funding, submit ethics applications, and provide research advice, plus, in their organisation’s skills to support, fund, monitor, mentor and engage universities to partner their research (p < 0.05). Conclusions This study appears to report the research capacity levels of the largest populations of podiatrists published. The 2011 survey findings indicate podiatrists have similarly low research capacity skill levels to those reported in the allied health literature. The 2012 survey, compared to the 2011 survey, suggests podiatrists perceived higher skills and support to initiate research in 2012. This improvement coincided with the implementation of research capacity building strategies.

Understanding and measuring information security culture in developing countries : case of Saudi Arabia

The purpose of the current study was to develop a measurement of information security culture in developing countries such as Saudi Arabia. In order to achieve this goal, the study commenced with a comprehensive review of the literature, the outcome being the development of a conceptual model as a reference base. The literature review revealed a lack of academic and professional research into information security culture in developing countries and more specifically in Saudi Arabia. Given the increasing importance and significant investment developing countries are making in information technology, there is a clear need to investigate information security culture from developing countries perspective such as Saudi Arabia. Furthermore, our analysis indicated a lack of clear conceptualization and distinction between factors that constitute information security culture and factors that influence information security culture. Our research aims to fill this gap by developing and validating a measurement model of information security culture, as well as developing initial understanding of factors that influence security culture. A sequential mixed method consisting of a qualitative phase to explore the conceptualisation of information security culture, and a quantitative phase to validate the model is adopted for this research. In the qualitative phase, eight interviews with information security experts in eight different Saudi organisations were conducted, revealing that security culture can be constituted as reflection of security awareness, security compliance and security ownership. Additionally, the qualitative interviews have revealed that factors that influence security culture are top management involvement, policy enforcement, policy maintenance, training and ethical conduct policies. These factors were confirmed by the literature review as being critical and important for the creation of security culture and formed the basis for our initial information security culture model, which was operationalised and tested in different Saudi Arabian organisations. Using data from two hundred and fifty-four valid responses, we demonstrated the validity and reliability of the information security culture model through Exploratory Factor Analysis (EFA), followed by Confirmatory Factor Analysis (CFA.) In addition, using Structural Equation Modelling (SEM) we were further able to demonstrate the validity of the model in a nomological net, as well as provide some preliminary findings on the factors that influence information security culture. The current study contributes to the existing body of knowledge in two major ways: firstly, it develops an information security culture measurement model; secondly, it presents empirical evidence for the nomological validity for the security culture measurement model and discovery of factors that influence information security culture. The current study also indicates possible future related research needs.

Promoting a more positive traffic safety culture in Australia : lessons learnt and future directions

Adopting a traffic safety culture approach, this paper identifies and discusses the ongoing challenge of promoting the road safety message in Australia. It is widely acknowledged that mass media and public education initiatives have played a critical role in the significant positive changes witnessed in community attitudes to road safety in the last three to four decades. It could be argued that mass media and education have had a direct influence on behaviours and attitudes, as well as an indirect influence through signposting and awareness raising functions in conjunction with enforcement. Great achievements have been made in reducing fatalities on Australia’s roads; a concept which is well understood among the international road safety fraternity. How well these achievements are appreciated by the general Australian community however, is not clear. This paper explores the lessons that can be learnt from successes in attitudinal and behaviour change in regard to seatbelt use and drink driving in Australia. It also identifies and discusses key challenges associated with achieving further positive changes in community attitudes and behaviours, particularly in relation to behaviours that may not be perceived by the community as dangerous, such as speeding and mobile phone use while driving. Potential strategies for future mass media and public education campaigns to target these challenges are suggested, including ways of harnessing the power of contemporary traffic law enforcement techniques, such as point-to-point speed enforcement and in-vehicle technologies, to help spread the road safety message.

Computer-assisted measurements of coronal knee joint laxity in vitro are related to low-stress behavior rather than structural properties of the collateral ligaments

The relationship between coronal knee laxity and the restraining properties of the collateral ligaments remains unknown. This study investigated correlations between the structural properties of the collateral ligaments and stress angles used in computer-assisted total knee arthroplasty (TKA), measured with an optically based navigation system. Ten fresh-frozen cadaveric knees (mean age: 81 ± 11 years) were dissected to leave the menisci, cruciate ligaments, posterior joint capsule and collateral ligaments. The resected femur and tibia were rigidly secured within a test system which permitted kinematic registration of the knee using a commercially available image-free navigation system. Frontal plane knee alignment and varus-valgus stress angles were acquired. The force applied during varus-valgus testing was quantified. Medial and lateral bone-collateral ligament-bone specimens were then prepared, mounted within a uni-axial materials testing machine, and extended to failure. Force and displacement data were used to calculate the principal structural properties of the ligaments. The mean varus laxity was 4 ± 1° and the mean valgus laxity was 4 ± 2°. The corresponding mean manual force applied was 10 ± 3 N and 11 ± 4 N, respectively. While measures of knee laxity were independent of the ultimate tensile strength and stiffness of the collateral ligaments, there was a significant correlation between the force applied during stress testing and the instantaneous stiffness of the medial (r = 0.91, p = 0.001) and lateral (r = 0.68, p = 0.04) collateral ligaments. These findings suggest that clinicians may perceive a rate of change of ligament stiffness as the end-point during assessment of collateral knee laxity.

In vitro assessment of surface congruency and integration of chondrocytes at adjacent edges of micro-fabricated clefts on cartilage

Osteochondral grafts are common treatment options for joint focal defects due to their excellent functionality. However, the difficulty is matching the topography of host and graft(s) surfaces flush to one another. Incongruence could lead to disintegration particularly when the gap reaches subchondoral region. The aim of this study is therefore to investigate cell response to gap geometry when forming cartilage-cartilage bridge at the interface. The question is what would be the characteristics of such a gap if the cells could bridge across to fuse the edges? To answer this, osteochondral plugs devoid of host cells were prepared through enzymatic decellularization and artificial clefts of different sizes were created on the cartilage surface using laser ablation. High density pellets of heterologous chondrocytes were seeded on the defects and cultured with chondrogenic differentiation media for 35 days. The results showed that the behavior of chondrocytes was a function of gap topography. Depending on the distance of the edges two types of responses were generated. Resident cells surrounding distant edges demonstrated superficial attachment to one side whereas clefts of 150 to 250 µm width experienced cell migration and anchorage across the interface. The infiltration of chondrocytes into the gaps provided extra space for their proliferation and laying matrix; as the result faster filling of the initial void space was observed. On the other hand, distant and fit edges created an incomplete healing response due to the limited ability of differentiated chondrocytes to migrate and incorporate within the interface. It seems that the initial condition of the defects and the curvature profile of the adjacent edges were the prime determinants of the quality of repair; however, further studies to reveal the underlying mechanisms of cells adapting to and modifying the new environment would be of particular interest.

Infectious in vitro transcripts from a cloned cDNA of barley yellow dwarf virus

A full-length cDNA clone of barley yellow dwarf virus (BYDV-PAV serotype) has been constructed and fused to the bacteriophage T7 RNA polymerase promoter. RNA transcripts produced in vitro, either capped or uncapped, were infectious in Triticum monococcum protoplasts. Protoplasts inoculated with in vitro-transcribed BYDV RNA accumulated coat protein, synthesized new viral RNAs, and produced virus particles. Aphid feeding on extracts from protoplasts inoculated with in vitro RNA transcripts can be used to transfer the virus progeny to whole plants. Introduction of mutations which interrupt specific BYDV-PAV open reading frames (ORFs) V and VI eliminated infectivity while an ORF I mutant remained infectious. Infectious RNA transcripts derived from BYDV cDNA clones will facilitate analysis of the molecular aspects of BYDV infection and further enhance our understanding of this economically important virus.

Innovation & workplace culture in the Australian interactive entertainment industry : the Halfbrick story

A recent success story of the Australian videogames industry is Brisbane based Halfbrick Studios, developer of the hit game for mobile devices, Fruit Ninja. Halfbrick not only survived the global financial crisis and an associated downturn in the Australian industry, but grew strongly, moving rapidly from developing licensed properties for platforms such as Game Boy Advance, Nintendo DS, and Playstation Portable (PSP) to becoming an independent developer and publisher of in-house titles, generating revenue both through App downloads and merchandise sales. Amongst the reasons for Halfbrick’s success is their ability to adaptively transform by addressing different technical platforms, user dynamics, business models and market conditions. Our ongoing case-study research from 2010 into Halfbrick’s innovation processes, culminating with some 10 semi-structured interviews with senior managers and developers, has identified a strong focus on workplace organisational culture, with staff reflecting that the company is a flat, team-based organisation devolving as much control as possible to the development teams directly, and encouraging a work-life balance in which creativity can thrive. The success of this strategy is evidenced through Halfbrick’s low staff turnover; amongst our interviewees most of the developers had been with the company for a number of years, with all speaking positively of the workplace culture and sense of creative autonomy they enjoyed. Interviews with the CEO, Shainiel Deo, and team leaders highlighted the autonomy afforded to each team and the organisation and management of the projects on which they work. Deo and team leaders emphasised the collaboration and communication skills they require in the developers that they employ, and that these characteristics were considered just as significant in hiring decisions as technical skills. Halfbrick’s developers celebrate their workplace culture and insist it has contributed to their capacity for innovation and to their commercial success with titles such as Fruit Ninja. This model of organisational management is reflected in both Stark’s (2009) idea of heterarchy, and Neff’s (2012) concept of venture labour, and provides a different perspective on the industry than the traditional political economy critique of precarious labour exploited by gaming conglomerates. Nevertheless, throughout many of the interviews and in our informal discussions with Halfbrick developers there is also a sense that this rewarding culture is quite tenuous and precarious in the context of a rapidly changing and uncertain global videogames industry. Whether such a workplace culture represents the future of the games industry, or is merely a ‘Prague Spring’ before companies such as Halfbrick are swallowed by traditional players’ remains to be seen. However, as the process of rapid and uncertain transformation plays out across the videogames industry, it is important to pay attention to emerging modes of organisation and workplace culture, even whilst they remain at the margins of the industry. In this paper we investigate Halfbrick’s workplace culture and ask how sustainable is this kind of rewarding and creative workplace?

Cyclic mechanical strain guides capillary-like morphology in vitro

Introduction Stretching of tissue stimulates angiogenesis but increased motion at a fracture site hinders revascularisation. In vitro studies have indicated that mechanical stimuli promote angiogenic responses in endothelial cells, but can either inhibit or enhance responses when applied directly to angiogenesis assays. We anticipated that cyclic tension applied during endothelial network assembly would increase vascular structure formation up to a certain threshold. Methods Fibroblast/HUVEC co-cultures were subjected to cyclic equibiaxial strain (1 Hz; 6 h/day; 7 days) using the FlexerCell FX-4000T system and limiting rings for simultaneous application of multiple strain magnitudes (0–13%). Cells were labelled using anti-PECAM-1, and image analysis provided measures of endothelial network length and numbers of junctions. Results Cyclic stretching had no significant effect on the total length of endothelial networks (P > 0.2) but resulted in a strain-dependent decrease in branching and localised alignments of endothelial structures, which were in turn aligned with the supporting fibroblastic construct. Conclusion The organisation of endothelial networks under cyclic strain is dominated by structural adaptation to the supporting construct. It may be that, in fracture healing, the formation and integrity of the granulation tissue and callus is ultimately critical in revascularisation and its failure under severe strain conditions.