Local and systemic delivery of a novel group of inhibitors of transglutaminase enzyme: A potential approach for treating of catheter-related complications and liver fibrosis

The present thesis investigates targeted (locally and systemically) delivery of a novel group of inhibitors of enzyme transglutaminases (TGs). TGs are a widely distributed group of enzymes that catalyse the formation of isopeptide bonds between the y-carboxamide group of protein-bound glutamines and the a-amino group of protein-bound lysines or polyamines. The first group of the novel inhibitors tested were the tluorescently labelled inhibitors of Factor XIIIa (FXIIIa). These small, non-toxic inhibitors have the potential to prevent stabilisation of thrombi by FXIIIa and consequently increase the natural rate of thrombolysis, in addition it reduces staphylococcal colonisation of catheters by inhibiting their FXIIIa¬mediated cross-linking to blood clot proteins on the central venous catheter (CVCs) surface. The aim of this work was to incorporate the FXIIIa inhibitor either within coating of polyurethane (PU) catheters or to integrate it into silicone catheters, so as to reduce the incidence of thrombotic occlusion and associated bacterial infection in CVCs. The initial work focused on the incorporation of FXIIIa inhibitors within polymeric coatings of PU catheters. After defining the key characteristics desired for an effective polymeric-coating, polyvinylpyrrolidone (PVP), poly(lactic-co-glycolic acid) (PLGA) or their combination were studies as polymers of choice for coating of the catheters_ The coating was conducted by dip-coating method in a polymer solution containing the inhibitor. Upon incubation of the inhibitor-and polymer-coated strips in buffer, PVP was dissolved instantly, generating fast and significant drug release, whilst PLGA did not dissolve, yielding a slow and an insufficient amount of drug release. Nevertheless, the drug release profile was enhanced upon employing a blend solution of PVP and PLGA. The second part of the study was to incorporate the FXIIIa inhibitor into a silicone elastomer; results demonstrated that FXIIIa inhibitor can be incorporated and released from silicone by using citric acid (CA) and sodium bicarbonate (SB) as additives and the drug release rate can be controlled by the amount of incorporated additives in the silicone matrix. Furthermore, it was deemed that the inhibitor was still biologically active subsequent to being released from the silicone elastomer strips. Morphological analysis confirmed the formation of channels and cracks inside the specimens upon the addition of CA and SB. Nevertheless, the tensile strength, in addition to Young's modulus of silicone elastomer strips, decreased constantly with an increasing amount of amalgamated CA/ SB in the formulations. According to our results, incorporation of FXIIIa inhibitor into catheters and other medical implant devices could offer new perspectives in preventing bio-material associated infections and thrombosis. The use of tissue transglutaminase (T02) inhibitor for treating of liver fibrosis was also investigated. Liver fibrosis is characterized by increased synthesis and decreased degradation of the extracellular matrix (ECM). Transglutaminase-mediated covalent cross-linking is involved in the stabilization of ECM in human liver fibrosis. Thus, TG2 inhibitors may be used to counteract the decreased degradation of the ECM. The potential of a liposome based drug delivery system for site specific delivery of the fluorescent TG2 inhibitor into the liver was investigated; results indicated that the TG2 inhibitor can be successfully integrated into liposomes and delivered to the liver, therefore demonstrating that liposomes can be employed for site-specific delivery of TG2 inhibitors into the liver and TG2 inhibitor incorporating liposomes could offer a new approach in treating liver fibrosis and its end stage disease cirrhosis.

Trigger release liposome systems:local and remote controlled delivery?

Target-specific delivery has become an integral area of research in order to increase bioavailability and reduce the toxic effects of drugs. As a drug-delivery option, trigger-release liposomes offer sophisticated targeting and greater control-release capabilities. These are broadly divided into two categories; those that utilise the local environment of the target site where there may be an upregulation in certain enzymes or a change in pH and those liposomes that are triggered by an external physical stimulus such as heat, ultrasound or light. These release mechanisms offer a greater degree of control over when and where the drug is released; furthermore, targeting of diseased tissue is enhanced by incorporation of target-specific components such as antibodies. This review aims to show the development of such trigger release liposome systems and the current research in this field.

Bossnapping:situating repertoires of industrial action in national and global contexts

French industrial relations were shaken in the spring of 2009 by a series of labour struggles which featured the forcible detention of company managers and threats to commit major acts of sabotage. In this article I focus on the first of these two types of action, placing industrial sequestration in the context of the pattern of collective negotiation processes in France, and comparing it with previous cycles of the same phenomenon, particularly in the post-1968 period. I argue that the current cycle of sequestrations needs to be understood as a response to the deterritorialisation processes of neo-liberal globalisation, and is the product of asymmetries of power between the fixity of labour and the fluidity of global capital. I conclude by arguing that sequestration is a public melodrama of protest which might point to the development of a resistant politics of corporeality in France, in common with struggles in other social and economic sectors.

Team-based working and employee well being:a cross-cultural comparison of United Kingdom and Hong Kong health services

This study examined the impact of team-based working, team structure, and job design on employee well-being (in term of job satisfaction and work stress) in staff working in healthcare organizations in Hong Kong. Cross-cultural differences in the impact of job design, team structure, and employee well-being outcomes between United Kingdom and Hong Kong were also investigated. A group of 197 staff from two Hong Kong hospitals were compared to a sample of 270 UK staff working in National Health Service organizations in the UK. Results showed that team structure and job design were significantly associated with greater employee satisfaction and lower stress for Hong Kong healthcare staff. Culture was also found to moderate the impact of team structure and job design on employee well-being. The findings suggest that although team structure and job design contribute to employee well-being, they have differential impacts across cultures. This provides insights to policy planning on building team-based organizations in the healthcare sector involving multinational collaboration.

Reporting and managing risk:a look at current practice at Tesco, RBS, local and central government

These case studies from CIMA highlight the need to embed risk management within more easily understood behaviours, consistent with the overall organisational culture. In each case, some form of internal audit team provides either an oversight function or acts as an expert link in that feedback loop. Frontline staff, managers and specialists should be completely aligned on risk, in part just to ensure that there is a consistency of approach. They should understand instinctively that good performance includes good risk management. Tesco has continued to thrive during the recession and remains a robust and efficient group of businesses despite the emergence of potential threats around consumer spending and the supply chain. RBS, by contrast, has suffered catastrophic and very public failures of risk management despite a large in-house function and stiff regulation of risk controls. Birmingham City Council, like all local authorities, is adapting to more commercial modes of operation and is facing diverse threats and opportunities emerging as a result of social change. And DCMS, like many other public sector organisations, has to handle an incredibly complex network of delivery partners within the context of a relatively recent overhaul of central government risk management processes. Key Findings: •Risk management is no longer solely a financial discipline, nor is it simply a concern for the internal control function. •Where organisations retain a discrete risk management cadre – often specialists at monitoring and evaluating a range of risks – their success is dependent on embedding risk awareness in the wider culture of the enterprise. •Risk management is most successful when it is explicitly linked to operational performance. •Clear leadership, specific goals, excellent influencing skills and open-mindedness to potential threats and opportunities are essential for effective risk management. •Bureaucratic processes and systems can hamper good risk management – either as a result of a ‘box-ticking mentality’ or because managers and staff believe they do not need to consider risk themselves.

Language policy and governmentality in businesses in Wales:a continuum of empowerment and regulation

In this paper, I examine how language policy acts as a means of both empowering the Welsh language and theminority language worker and as a means of exerting power over them. For this purpose, the study focuses on a particular site: private sector businesses in Wales. Therein, I trace two major discursive processes: first, the Welsh Government’s national language policy documents that promote corporate bilingualism and bilingual employees as value-added resources; second, the practice and discourse of company managers who sustain or appropriate such promotional discourses for creating and promoting their own organisational values. By drawing on concepts from governmentality, critical language policy and discourse studies, I show that promoting bilingualism in business is characterised by local and global governmentalities. These not only bring about critical shifts in valuing language as symbolic entities attached to ethnonational concerns or as promotional objects that bring material gain. Language governmentalities also appear to shape new forms of ‘languaging’ the minority language worker as selfgoverning, and yet, governed subjects who are ultimately made responsible for ‘owning’ Welsh.

Episodes in the Malaysian auditing sage

Purpose – The purpose of this paper is to examine the various episodes in the Malaysian auditing saga, covering the period of the first 40 years post-independence in 1957 to just before the onset of the Asian Financial Crisis in 1997. Design/methodology/approach – Based on documentary analysis, the paper offers a historical account of the development of the auditing profession with reference to the dynamic changes in its political and socio-economic environment. Findings – The paper concludes that the function of auditing in Malaysian society responded to political-economic pressures over time viz. changing from maintaining the economic policy to serve Western investors to accommodating ethnic relations, and to strengthening the bond between local and global corporate elites and the political leaders. Originality/value – Since, little is known of the professionalisation process in Malaysia, our analysis of the structural conditions during the 40 years from the achievement of independence from the British in 1957 to just before the onset of the Asian Financial Crisis in 1997 and our assessment of their implications for auditing contributes to knowledge in this area

Travelling waves in a complex Ginzburg-Landau equation with time-delay feedback

One of the simplest ways to create nonlinear oscillations is the Hopf bifurcation. The spatiotemporal dynamics observed in an extended medium with diffusion (e.g., a chemical reaction) undergoing this bifurcation is governed by the complex Ginzburg-Landau equation, one of the best-studied generic models for pattern formation, where besides uniform oscillations, spiral waves, coherent structures and turbulence are found. The presence of time delay terms in this equation changes the pattern formation scenario, and different kind of travelling waves have been reported. In particular, we study the complex Ginzburg-Landau equation that contains local and global time-delay feedback terms. We focus our attention on plane wave solutions in this model. The first novel result is the derivation of the plane wave solution in the presence of time-delay feedback with global and local contributions. The second and more important result of this study consists of a linear stability analysis of plane waves in that model. Evaluation of the eigenvalue equation does not show stabilisation of plane waves for the parameters studied. We discuss these results and compare to results of other models.

Stabilization of standing waves through time-delay feedback

Standing waves are studied as solutions of a complex Ginzburg-Landau equation subjected to local and global time-delay feedback terms. The onset is described as an instability of the uniform oscillations with respect to spatially periodic perturbations. The solution of the standing wave pattern is given analytically and studied through simulations. © 2013 American Physical Society.

Comments on multiple oscillatory solutions in systems with time-delay feedback

A complex Ginzburg-Landau equation subjected to local and global time-delay feedback terms is considered. In particular, multiple oscillatory solutions and their properties are studied. We present novel results regarding the disappearance of limit cycle solutions, derive analytical criteria for frequency degeneration, amplitude degeneration, frequency extrema. Furthermore, we discuss the influence of the phase shift parameter and show analytically that the stabilization of the steady state and the decay of all oscillations (amplitude death) cannot happen for global feedback only. Finally, we explain the onset of traveling wave patterns close to the regime of amplitude death.

South Africa and the global game:football, apartheid and beyond

Firmly situating South African teams, players, and associations in the international framework in which they have to compete, South Africa and the Global Game: Football, Apartheid, and Beyond presents an interdisciplinary analysis of how and why South Africa underwent a remarkable transformation from a pariah in world sport to the first African host of a World Cup in 2010. Written by an eminent team of scholars, this special issue and book aims to examine the importance of football in South African society, revealing how the black oppression transformed a colonial game into a force for political, cultural and social liberation. It explores how the hosting of the 2010 World Cup aims to enhance the prestige of the post-apartheid nation, to generate economic growth and stimulate Pan-African pride. Among the themes dealt with are race and racism, class and gender dynamics, social identities, mass media and culture, and globalization. This collection of original and insightful essays will appeal to specialists in African Studies, Cultural Studies, and Sport Studies, as well as to non-specialist readers seeking to inform themselves ahead of the 2010 World Cup. This book was published as a special issue of Soccer and Society. 1. Introduction Peter Alegi and Chris Bolsmann Part 1: Past is Prologue – History of Football in South Africa 2. Football as Code: The Social Diffusion of ‘Soccer’ in South Africa Lloyd Hill 3. White Football in South Africa: Empire, Apartheid and Change, 1892 – 1977 Chris Bolsmann 4. A Biography of Darius Dhlomo: Transnational Footballer in the Era of Apartheid Peter Alegi 5. Women and Gender in South African Soccer Cynthia Fabrizio Pelak Part 2: Football Culture after Apartheid: Local and Transnational Dynamics 6. "You Must Support Chiefs: Pirates Already Have Two White Fans!" Race and Racial Discourse in South African Football Fandom Marc Fletcher 7. "It wasn’t that I did not like South African Football": Media, History, and Biography Sean Jacobs 8. Soccer in a Rugby Town: Restructuring Football in Stellenbosch Sylvain Cubizolles 9. Differing Trajectories: Football Development and Patterns of Player Migration in South Africa and Ghana Paul Darby and Eirik Solberg Part 3: The 2010 World Cup: Challenges and Opportunities 10. Football's Tsars: Proprietorship, Corporatism and Politics in the 2010 FIFA World Cup Scarlett Cornelissen 11. Sports as Cultural Diplomacy: The 2010 FIFA World Cup in South Africa’s Foreign Policy Sifiso Mxolisi Ndlovu 12. World Cup 2010: Africa’s Turn or the Turn on Africa? Ashwin Desai and Goolam Vahed 13. The 2010 FIFA World Cup: Critical Voices From Below Percy Ngonyama.