Colloidal drug probe : method development and validation for adhesion force measurement using atomic force microscopy

This study demonstrates a novel technique of preparing drug colloid probes to determine the adhesion force between the drug salbutamol sulphate (SS) and the surfaces of polymer microparticles to be used as carriers for the dispersion of drug particles from a dry powder inhaler (DPI) formulation. Initially model silica probes of approximately 4 μm size, similar to a drug particle used in DPI formulations, were coated with a saturated SS solution with the aid of capillary forces acting between the silica probe and the drug solution. The developed method of ensuring a smooth and uniform layer of SS on the silica probe was validated using X-Ray Photoelectron Spectroscopy (XPS) and Scanning Electron Microscopy (SEM). Using the same technique, silica microspheres preattached on the AFM cantilever were coated with SS. The adhesion forces between the silica probe and drug coated silica (drug probe) and polymer surfaces (hydrophilic and hydrophobic) were determined. Our experimental results showed that the technique for preparing the drug probe was robust and can be used to determine the adhesion force between hydrophilic/hydrophobic drug probe and carrier surfaces to gain a better understanding on drug carrier adhesion forces in DPI formulations.

Effect of chemical conjugation of L-leucine to chitosan on the dispersibility and drug release of a dry powder inhaler nanoparticle formulation

Purpose: This study investigated the effect of chemical conjugation of the amino acid L-leucine to the polysaccharide chitosan on the dispersibility and drug release pattern of a polymeric nanoparticle (NP)-based controlled release dry powder inhaler (DPI) formulation. Methods: A chemical conjugate of L-leucine with chitosan was synthesized and characterized by Infrared (IR) Spectroscopy, Nuclear Magnetic Resonance (NMR) Spectroscopy, Elemental Analysis and X-ray Photoelectron Spectroscopy (XPS). Nanoparticles of both chitosan and its conjugate were prepared by a water-in-oil emulsification – glutaraldehyde cross-linking method using the antihypertensive agent, diltiazem (Dz) hydrochloride as the model drug. The surface morphology and particle size distribution of the nanoparticles were determined by Scanning Electron Microscopy (SEM) and Dynamic Light Scattering (DLS). The dispersibility of the nanoparticle formulation was analysed by a Twin Stage Impinger (TSI) with a Rotahaler as the DPI device. Deposition of the particles in the different stages was determined by gravimetry and the amount of drug released was analysed by UV spectrophotometry. The release profile of the drug was studied in phosphate buffered saline at 37 ⁰C and analyzed by UV spectrophotometry. Results: The TSI study revealed that the fine particle fractions (FPF), as determined gravimetrically, for empty and drug-loaded conjugate nanoparticles were significantly higher than for the corresponding chitosan nanoparticles (24±1.2% and 21±0.7% vs 19±1.2% and 15±1.5% respectively; n=3, p<0.05). The FPF of drug-loaded chitosan and conjugate nanoparticles, in terms of the amount of drug determined spectrophotometrically, had similar values (21±0.7% vs 16±1.6%). After an initial burst, both chitosan and conjugate nanoparticles showed controlled release that lasted about 8 to 10 days, but conjugate nanoparticles showed twice as much total drug release compared to chitosan nanoparticles (~50% vs ~25%). Conjugate nanoparticles also showed significantly higher dug loading and entrapment efficiency than chitosan nanoparticles (conjugate: 20±1% & 46±1%, chitosan: 16±1% & 38±1%, n=3, p<0.05). Conclusion: Although L-leucine conjugation to chitosan increased dispersibility of formulated nanoparticles, the FPF values are still far from optimum. The particles showed a high level of initial burst release (chitosan, 16% and conjugate, 31%) that also will need further optimization.

The future of the music industry in an age of digital distribution

This is an invited public lecture. The talk will cover how the music industry has changed due to digital technologies. During the talk I will look at how the changing balance between live music, music licensing and recorded music. I will also discuss online music subscription services and whether they might be a future for music distribution in China and elsewhere in the world. It will also look at how music artists and composers are affected by this change.

Dispute resolution across platforms : offshore gambling industry & EVE online

Contemporary online environments suffer from a regulatory gap; that is there are few options for participants between customer service departments and potentially expensive court cases in foreign jurisdictions. Whatever form of regulation ultimately fills that gap will be charged with determining whether specific behavior, within a specific environment, is fair or foul; whether it’s cheating or not. However, cheating is a term that, despite substantial academic study, remains problematic. Is anything the developer doesn’t want you to do cheating? Is it only if your actions breach the formal terms of service? What about the community norms, do they matter at all? All of these remain largely unresolved questions, due to the lack of public determination of cases in such environments, which have mostly been settled prior to legal action. In this paper, I propose a re-branding of participant activity in such environments into developer-sanctioned, advantage play, and cheating. Advantage play, ultimately, is activity within the environment in which the player is able to turn the mechanics of the environment to their advantage without breaching the rules of the environment. Such a definition, and the term itself, is based on the usage of the term within the gambling industry, in which advantage play is considered betting with the advantage in the players’ favor rather than that of the house. Through examples from both the gambling industry and the Massively Multiplayer Role-Playing Game Eve Online, I consider the problems in defining cheating, suggest how the term ‘advantage play’ may be useful in understanding participants behavior in contemporary environments, and ultimately consider the use of such terminology in dispute resolution models which may overcome this regulatory gap.

Governance challenges in the global games industry

Current governance challenges facing the global games industry are heavily dominated by online games. Whilst much academic and industry attention has been afforded to Virtual Worlds, the more pressing contemporary challenges may arise in casual games, especially when found on social networks. As authorities are faced with an increasing volume of disputes between participants and platform operators, the likelihood of external regulation increases, and the role that such regulation would have on the industry – both internationally and within specific regions – is unclear. Kelly (2010) argues that “when you strip away the graphics of these [social] games, what you are left with is simply a button [...] You push it and then the game returns a value of either Win or Lose”. He notes that while “every game developer wants their game to be played, preferably addictively, because it’s so awesome”, these mechanics lead not to “addiction of engagement through awesomeness” but “the addiction of compulsiveness”, surmising that “the reality is that they’ve actually sort-of kind-of half-intentionally built a virtual slot machine industry”. If such core elements of social game design are questioned, this gives cause to question the real-money options to circumvent them. With players able to purchase virtual currency and speed the completion of tasks, the money invested by the 20% purchasing in-game benefits (Zainwinger, 2012) may well be the result of compulsion. The decision by the Japanese Consumer Affairs agency to investigate the ‘Kompu Gacha’ mechanic (in which players are rewarded for completing a set of items obtained through purchasing virtual goods such as mystery boxes), and the resultant verdict that such mechanics should be regulated through gambling legislation, demonstrates that politicians are beginning to look at the mechanics deployed in these environments. Purewal (2012) states that “there’s a reasonable argument that complete gacha would be regulated under gambling law under at least some (if not most) Western jurisdictions”. This paper explores the governance challenged within these games and platforms, their role in the global industry, and current practice amongst developers in the Australian and United States to address such challenges.

How technological change affects power relations in global markets : remote developers in the console and mobile games industry

This paper focuses on Australian development firms in the console and mobile games industry in order to understand how small firms in a geographically remote and marginal position in the global industry are able to relate to global firms and capture revenue share. This paper shows that, while technological change in the games industry has resulted in the emergence of new industry segments based on transactional rather than relational forms of economic coordination, in which we might therefore expect less asymmetrical power relations, lead firms retain a position of power in the global games entertainment industry relative to remote developers. This has been possible because lead firms in the emerging mobile devices market have developed and sustained bottlenecks in their segment of the industry through platform competition and the development of an intensely competitive ecosystem of developers. Our research shows the critical role of platform competition and bottlenecks in influencing power asymmetries within global markets.

A systemic view of innovation adoption in the Australian beef industry

Significant investments in developing technological innovations have been made in the Australian beef industry but with low adoption rates. By modelling the key variables and their interactions in the innovation adoption process, this research seeks to demonstrate the complexity and dynamics of the process. This research uses causal loop modelling and develops a holistic model of the current innovation adoption system in the Australian beef industry to show the complexity of dynamic interactions among multiple variables. It is suggested that innovation adoption is such an extremely complex issue, and we need to shift our views on this issue from a paradigm of linear thinking to systems thinking. Innovation adoption is more likely to be enhanced based on a full understanding of the complexity and dynamics of the system as a whole. The paper demonstrates to practitioners and developers of innovation the multiple variables and interactions impacting innovation adoption.

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?

Analysing governance categories used on project alliances in the construction industry

In Australia, collaborative contracts, and in particular, project alliances, have been increasingly used to govern infrastructure projects. These contracts use formal and informal governance mechanisms to manage the delivery of infrastructure projects. Formal mechanisms such as financial risk sharing are specified in the contract, while informal mechanisms such as integrated teams are not. Given that the literature contains a multiplicity of often untestable definitions, this paper reports on a review of the literature to operationalize the concepts of formal and informal governance. This work is the first phase of a study that will examine the optimal balance of formal and informal governance structures. Desk-top review of leading journals in the areas of construction management and business management, as well as recent government documents and industry guidelines, was undertaken to to conceptualise and operationalize formal and informal governance mechanisms. The study primarily draws on transaction-cost economics (e.g. Williamson 1979; Williamson 1991), relational contract theory (Feinman 2000; Macneil 2000) and social psychology theory (e.g. Gulati 1995). Content analysis of the literature was undertaken to identify key governance mechanisms. Content analysis is a commonly used methodology in the social sciences area. It provides rich data through the systematic and objective review of literature (Krippendorff 2004). NVivo 9, a qualitative data analysis software package, was used to assist in this process. A previous study by the authors identified that formal governance mechanisms can be classified into seven measurable categories: (1) negotiated cost, (2) competitive cost, (3) commercial framework, (4) risk and reward sharing, (5) qualitative performance, (6) collaborative multi-party agreement, and (7) early contractor involvement. Similarly, informal governance mechanisms can be classified into four measureable categories: (1) leadership structure, (2) integrated team, (3) team workshops, and (4) joint management system. This paper explores and further defines the key operational characteristics of each mechanism category, highlighting its impact on value for money in alliance project delivery. The paper’s contribution is that it provides the basis for future research to compare the impact of a range of individual mechanisms within each category, as a means of improving the performance of construction projects.

Failure to administer a drug and causation

Case note on King v Western Sydney Local Health Network In King v Western Sydney Local Health Network [2013] NSWCA 162 the appellant sought damages for the severe physical and intellectual disability she suffered as a result of foetal varicella syndrome (FVS) caused by her mother contracting varicella (chickenpox) in the second trimester of her pregnancy. The mother had been exposed to the virus and sought advice from a doctor at Blacktown Hospital as she had not had the virus herself and therefore did not possess immunity. In such circumstances at the time, the standard medical practice was to offer the mother varicellazoster immunoglobulin (VZIG) to boost her defence to the virus. The appellant’s mother however was not offered this treatment and contracted chickenpox resulting the appellant’s condition...

Phenytoin metabolism by human cytochrome P450 : involvement of P450 3A and 2C forms in secondary metabolism and drug-protein adduct formation

The anticonvulsant phenytoin (5,5-diphenylhydantoin) provokes a skin rash in 5 to 10% of patients, which heralds the start of an idiosyncratic reaction that may result from covalent modification of normal self proteins by reactive drug metabolites. Phenytoin is metabolized by cytochrome P450 (P450) enzymes primarily to 5-(p-hydroxyphenyl-),5-phenylhydantoin (HPPH), which may be further metabolized to a catechol that spontaneously oxidizes to semiquinone and quinone species that covalently modify proteins. The aim of this study was to determine which P450s catalyze HPPH metabolism to the catechol, proposed to be the final enzymatic step in phenytoin bioactivation. Recombinant human P450s were coexpressed with NADPH-cytochrome P450 reductase in Escherichia coli. Novel bicistronic expression vectors were constructed for P450 2C19 and the three major variants of P450 2C9, i.e., 2C9*1, 2C9*2, and 2C9*3. HPPH metabolism and covalent adduct formation were assessed in parallel. P450 2C19 was the most effective catalyst of HPPH oxidation to the catechol metabolite and was also associated with the highest levels of covalent adduct formation. P450 3A4, 3A5, 3A7, 2C9*1, and 2C9*2 also catalyzed bioactivation of HPPH, but to a lesser extent. Fluorographic analysis showed that the major targets of adduct formation in bacterial membranes were the catalytic P450 forms, as suggested from experiments with human liver microsomes. These results suggest that P450 2C19 and other forms from the 2C and 3A subfamilies may be targets as well as catalysts of drug-protein adduct formation from phenytoin.

The Music Industry : Music in the Cloud, 2nd edition

The music industry is going through a period of immense change brought about in part by the digital revolution. What is the role of music in the age of computers and the Internet? How has the music industry been transformed by the economic and technological upheavals of recent years, and how is it likely to change in the future? This thoroughly revised and updated new edition provides an international overview of the music industry and its future prospects in the world of global entertainment. Patrik Wikström illuminates the workings of the music industry, and captures the dynamics at work in the production of musical culture between the transnational media conglomerates, the independent music companies and the public. New to this second edition are expanded sections on the structure of the music industry, online business models and the links between social media and music. Engaging and comprehensive, The Music Industry will be a must-read for students and scholars of media and communication studies, cultural studies, popular music, sociology and economics.

Commercial successes in the music industry

Commercial success in the music industry is obviously related to one’s ability to use musical artisanship as a basis for generating profits and to accumulate substantial wealth. That may seem fairly straightforward, but commercial success is an elusive concept that is continuously negotiated within the industry to determine both what should be considered “success” as well as how it should be measured. This entry discusses commercial success in the popular music industry and strategies used to achieve it.

The enemy of music : modeling the behavior of a cultural industry in crisis

The purpose of this explorative study is to contribute to the understanding of current music industry dynamics. The situation is undeniably quite dramatic: Since the turn of the millennium, the global music industry has declined by $ US 6.2 billion in value—a fall of 16.3% in constant dollar terms. IFPI, the trade organization representing the international recording industry, identifies a number of exogenous factors as the main drivers of the downturn. This article suggests that other factors, in addition to those identified by IFPI, may have contributed to the current difficulties. A model is presented which indicates that business strategies which were designed to cope with the challenging business environment have reduced product diversity, damaged profitability, and contributed to the problem they were intended to solve.