Investigating the delivery of antimicrobial proteins and aminoglycoside antibiotics to the airways

Biopharmaceuticals are finding wide applications in the management of diverse disease conditions. Pulmonary delivery of proteins may constitute an effective and efficient non-invasive alternative to parenteral delivery, which is currently the main route of administration of biopharmaceutical drugs. A particular area, in which pulmonary delivery of peptides and proteins may find ready application, is in the local delivery of antimicrobial peptides and proteins to the airway, a measure that could potentially bring about improvements to currently available antipseudomonal therapies. This thesis has therefore sought to develop inhalable antimicrobial proteins in combination with antibiotics that have particularly good antimicrobial activity against Pseudomonas aeruginosa infections in the respiratory tract of people with cystic fibrosis (CF). Through process optimisation, a suitable spray drying method was developed and used for the preparation of active, inhalable dry powder formulations of the antimicrobial protein, lactoferrin, and aminoglycosides (tobramycin and gentamicin). The physicochemical properties, aerosolisation performance and the antibacterial properties of the various spray-dried formulations were assessed. In addition, a relevant in vitro cellular model was employed to investigate the potential cytotoxic and pro-inflammatory effects of the various formulations on four bronchial human epithelial cells together with their effectiveness at reducing bacterial colonies when administered on to biofilm co-cultured on the epithelial cells. It was found that following spray drying the particles obtained were mostly spherical, amorphous and possessed suitable aerosolisation characteristics. The various spray-dried antimicrobial proteins (lactoferrin or apo lactoferrin) and co-spray dried combinations of the proteins and aminoglycosides were found to exhibit bactericidal activity against planktonic and biofilms of P. aeruginosa. In general, the spray drying process was found not to significantly affect the antimicrobial activities of the protein. Treatment of the different bronchial epithelial cell lines with the antimicrobial formulations showed that the various formulations were non-toxic and that the co-spray dried combinations significantly reduced established P. aeruginosa biofilms on the four bronchial epithelial cells. Overall, the results from this thesis demonstrates that spray drying could potentially be employed to prepare inhalable antimicrobial agents comprised of proteins and antibiotics. These new combinations of proteins and aminoglycosides has promising applications in the management of P. aeruginosa in the airway of cystic fibrosis patients.

An in vitro comparison of the incorporation, growth, and chondrogenic potential of human bone marrow versus adipose tissue mesenchymal stem cells in clinically relevant cell scaffolds used for cartilage repair

Aim. To compare the incorporation, growth, and chondrogenic potential of bone marrow (BM) and adipose tissue (AT) mesenchymal stem cells (MSCs) in scaffolds used for cartilage repair. Methods. Human BM and AT MSCs were isolated, culture expanded, and characterised using standard protocols, then seeded into 2 different scaffolds, Chondro-Gide or Alpha Chondro Shield. Cell adhesion, incorporation, and viable cell growth were assessed microscopically and following calcein AM/ethidium homodimer (Live/Dead) staining. Cell-seeded scaffolds were treated with chondrogenic inducers for 28 days. Extracellular matrix deposition and soluble glycosaminoglycan (GAG) release into the culture medium was measured at day 28 by histology/immunohistochemistry and dimethylmethylene blue assay, respectively. Results. A greater number of viable MSCs from either source adhered and incorporated into Chondro-Gide than into Alpha Chondro Shield. In both cell scaffolds, this incorporation represented less than 2% of the cells that were seeded. There was a marked proliferation of BM MSCs, but not AT MSCs, in Chondro-Gide. MSCs from both sources underwent chondrogenic differentiation following induction. However, cartilaginous extracellular matrix deposition was most marked in Chondro- Gide seeded with BM MSCs. Soluble GAG secretion increased in chondrogenic versus control conditions. There was no marked difference in GAG secretion by MSCs from either cell source. Conclusion. Chondro-Gide and Alpha Chondro Shield were permissive to the incorporation and chondrogenic differentiation of human BM and AT MSCs. Chondro-Gide seeded with BM MSCs demonstrated the greatest increase in MSC number and deposition of a cartilaginous tissue.

Statistical guidelines for clinical studies of human vision

Citation information: Armstrong RA, Davies LN, Dunne MCM & Gilmartin B. Statistical guidelines for clinical studies of human vision. Ophthalmic Physiol Opt 2011, 31, 123-136. doi: 10.1111/j.1475-1313.2010.00815.x ABSTRACT: Statistical analysis of data can be complex and different statisticians may disagree as to the correct approach leading to conflict between authors, editors, and reviewers. The objective of this article is to provide some statistical advice for contributors to optometric and ophthalmic journals, to provide advice specifically relevant to clinical studies of human vision, and to recommend statistical analyses that could be used in a variety of circumstances. In submitting an article, in which quantitative data are reported, authors should describe clearly the statistical procedures that they have used and to justify each stage of the analysis. This is especially important if more complex or 'non-standard' analyses have been carried out. The article begins with some general comments relating to data analysis concerning sample size and 'power', hypothesis testing, parametric and non-parametric variables, 'bootstrap methods', one and two-tail testing, and the Bonferroni correction. More specific advice is then given with reference to particular statistical procedures that can be used on a variety of types of data. Where relevant, examples of correct statistical practice are given with reference to recently published articles in the optometric and ophthalmic literature.

Institutions, resources, and entry strategies in emerging economies

We investigate the impact of market-supporting institutions on business strategies by analyzing the entry strategies of foreign investors entering emerging economies. We apply and advance the institution-based view of strategy by integrating it with resource-based considerations. In particular, we show how resource-seeking strategies are pursued using different entry modes in different institutional contexts. Alternative modes of entry—greenfield, acquisition, and joint venture (JV)—allow firms to overcome different kinds of market inefficiencies related to both characteristics of the resources and to the institutional context. In a weaker institutional framework, JVs are used to access many resources, but in a stronger institutional framework, JVs become less important while acquisitions can play a more important role in accessing resources that are intangible and organizationally embedded. Combining survey and archival data from four emerging economies, India, Vietnam, South Africa, and Egypt, we provide empirical support for our hypotheses.

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.

Innovation in leadership development

In the light of the financial crisis and the radically changed conditions in the market place, international leadership development is facing new demands. The Danish-based International Leadership Institute Mannaz has researched the new conditions in collaboration with the Institute of Executive Development in the United States. The research, conducted in 2008 and 2009, combines, in an innovative way, quantitative and qualitative inputs, from both current and future perspectives, from some 111 senior Corporate Executives, Heads of Human Resources and of Learning and Organisational Development in large international corporations headquartered in Europe and the United States; together with the thoughts of some 50 experienced practitioners involved in executive coaching as well as in designing, developing and facilitating leadership development programmes. Also we include a section summarising the key findings from recently published research from other leadership development surveys. Conclusions reveal that the crisis has propelled a long-awaited decline of the traditional classroom-based educational approach to leadership development. Instead, effective leadership development is suggested to build on experiential learning approaches rooted in real life, real time and allowing for more immediate impact and providing for considerably higher relevance and motivation. Coaching, leaders teaching leaders, stretch assignments, action learning, peer networking, customer insights and selective use of technology are seen as important contributors to the leadership development process going forward.

New technology, industrial relations and white collar trade unions : the case of the National and Local Government Officers Association

The decade since 1979 has seen the most rapid introduction of microelectronic technology in the workplace. In particular, the scope offered for the application of this new technology to the area of white collar work has meant that it is a sector where trade unions have been confronted with major challenges. However the application of this technology has also provided trade unions with opportunities for exerting influence to reshape traditional attitudes to both industrial relations and the nature of work. Recent academic research on the trade union response to the introduction of new technology at the workplace suggests that, despite the resources and apparent sophistication of modern trade unions, they have not in general been able to take advantage of the opportunities offered during this period of radical technological change,the argument being that this is due both to structural weaknesses and the inappropriateness of the system of collective bargaining where new technology issues are concerned. Despite the significance of the Public Sector in employment terms, research into the response of public sector white collar trade unions to technological change has been fairly limited. This thesis sets out the approach of the National and Local Government Officers Association (NALGO), the largest solely white collar union in the world with over three quarters of a million members employed in a wide range of public service industries. The thesis examines NALGO's response at national level and, through detailed case studies, at local level in respect of Local Government and Water Industry NALGO members. The response is then evaluated and conclusions drawn in terms of a framework based upon an assessment of the key factors relevant in judging the ability of NALGO to respond effectively to the challenges brought about by the technological revolution of the last ten years.

Local resources and procurement practices in humanitarian supply chains:an empirical examination of large-scale house reconstruction projects

Different procurement decisions taken by relief organizations can result in considerably different implications in regards to transport, storage, and distribution of humanitarian aid and ultimately can influence the performance of the humanitarian supply chain and the delivery of the humanitarian aid. In this article, we look into what resources are needed and how these resources evolve in the delivery of humanitarian aid. Drawing on the resource-based view of the firm, we develop a framework to categorize the impact of local resources on the configuration of humanitarian supply chains. In contrast to other papers, the importance of localizing the configuration of the humanitarian supply chain is not only conceptually recognized, but empirical investigations are also provided. In terms of methodology, this article is based on the analysis of secondary data from two housing reconstruction projects. Findings indicate that the use of local resources in humanitarian aid has positive effects on programs' overall supply chain performance and these effects are not only related to the macroeconomic perspective, but benefits expand to improvements related to the use of knowledge. At the same time, it was found that local sourcing often comes with a number of problems. For example, in one of the cases, significant problems existed, which were related to the scarcity of local supplies. Both housing reconstruction projects have indicated the continuous need for changes throughout the programs as a dynamic supply chain configuration is important for the long-term sustainability of reconstruction aid. © 2014 Decision Sciences Institute.

Integration and devolvement of human resource practices in Nepal

Purpose: The purpose of this study is to explore the nature of human resource management in publicly listed finance sector companies in Nepal. In particular, it explores the extent to which HR practice is integrated into organisational strategy and devolved to line management. Design/methodology/ approach: A structured interview was conducted with the senior executive responsible for human resource management in 26 commercial banks and insurance companies in Nepal. Findings: The degree of integration of HR practice appears to be increasing within this sector, but this is dependent on the maturity of the organisations. The devolvement of responsibility to line managers is at best partial, and in the case of the insurance companies, it is more out of necessity due to the absence of a strong central HR function. Research limitations/implications: The survey is inevitably based on a small sample; however this represents 90 per cent of the relevant population. The data suggest that Western HR is making inroads into more developed aspects of Nepalese business. Compared with Nepalese business as a whole, the financial sector appears relatively Westernised, although Nepal still lags India in its uptake of HR practices. Practical implications: It appears unlikely from a cultural perspective that the devolvement of responsibility will be achieved as a result of HR strategy. National cultural, political and social factors continue to be highly influential in shaping the Nepalese business environment. Originality/value: Few papers have explored HR practice in Nepal. This paper contributes to the overall assessment of HR uptake globally and highlights emic features impacting on that uptake. © Emerald Group Publishing Limited.

The discretionary role of the line manager in inspiring work engagement and innovative behaviour:a study of social exchange and job resources in the public sector

This thesis is about the discretionary role of the line manager in inspiring the work engagement of staff and their resulting innovative behaviour examined through the lens of Social Exchange Theory (Blau, 1964) and the Job Demands-Resources theory (Bakker, Demerouti, Nachreiner & Schaufeli, 2001). The study is focused on a large British Public Sector organisation undergoing a major organisational shift in the way in which they operate as part of the public sector. It is often claimed that people do not leave organisations; they leave line managers (Kozlowski & Doherty, 1989). Regardless of the knowledge in the literature concerning the importance of the line manager in organisations (Purcell, 2003), the engagement literature in particular is lacking in the consideration of such a fundamental figure in organisational life. Further, the understanding of the black box of managerial discretion and its relationship to employee and organisation related outcomes would benefit from greater exploration (Purcell, 2003; Gerhart, 2005; Scott, et al, 2009). The purpose of this research is to address these gaps with relation to the innovative behaviour of employees in the public sector – an area that is not typically associated with the public sector (Bhatta, 2003; McGuire, Stoner & Mylona, 2008; Hughes, Moore & Kataria, 2011). The study is a CASE Award PhD thesis, requiring academic and practical elements to the research. The study is of one case organisation, focusing on one service characterised by a high level of adoption of Strategic Human Resource Management activities and operating in a rather unique manner for the public sector, having private sector competition for work. The study involved a mixed methods approach to data collection. Preliminary focus groups with 45 participants were conducted, followed by an ethnographic period of five months embedded into the service conducting interviews and observations. This culminated in a quantitative survey delivered within the wider directorate to approximately 500 staff members. The study used aspects of the Grounded Theory (Glaser & Strauss, 1967) approach to analyse the data and developed results that highlight the importance of the line manager in an area characterised by SHRM and organisational change for engaging employees and encouraging innovative behaviour. This survey was completed on behalf of the organisation and the findings of this are presented in appendix 1, in order to keep the focus of the PhD on theory development. Implications for theory and practice are discussed alongside the core finding. Line managers’ discretion surrounding the provision of job resources (in particular trust, autonomy and implementation and interpretation of combined bundles of SHRM policies and procedures) influenced the exchange process by which employees responded with work engagement and innovative behaviour. Limitations to the research are the limitations commonly attributed to cross-sectional data collection methods and those surrounding generalisability of the qualitative findings outside of the contextual factors characterising the service area. Suggestions for future research involve addressing these limitations and further exploration of the discretionary role with regards to extending our understanding of line manager discretion.

Urban politics and the social practices of critique and justification:conceptual insights from French pragmatism

Recent times have witnessed a growing belief in urban spaces as 'assemblages' produced through interwoven and spatially differentiated forces that converge at particular sites. There is also continuing interest in the nature of neoliberal tendencies and the rise of post-politics and democracy in urban governance. These accounts typically lack attention towards the comprehensive conceptualization of the heterogeneous logics and mechanics of relations and negotiations between actors. This paper seeks to advance these perspectives by exploring the potential contribution of French pragmatism thinking to how social life is produced through practical dialogue between actors through critique, argumentation and justification. © The Author(s) 2012.

Human resource management systems and organizational performance:a test of a mediating model in the Greek manufacturing context

This paper investigates the relationship between systems of HRM policies and organizational performance. The research is based on a sample of 178 organizations operating in the Greek manufacturing sector. A mediation model is tested to examine the link between HRM and organizational performance. The results of this study support the hypothesis that the relationship between the HRM systems of resourcing-development and reward-relations, and organizational performance, is mediated through the HRM outcomes of skills and attitudes. The paper not only supports the theory that HRM systems have a positive impact on organizational performance but also explains the mechanisms through which HRM systems improve organizational performance.

Managing human resources in the Middle-East

Managing Human Resources in the Middle East provides the reader with an understanding of the dynamics of HRM in this important region. Systematic analysis highlights the main factors and variables dictating HRM policies and practices within each country. Diverse and unique cultural, institutional and business environment factors which play a significant role in determining HRM systems in the region are also elaborated upon. The text moves from a general overview of HRM in the Middle-East to an exploration of the current status, role and strategic importance of the HR function in a wide-range of country-specific chapters, before highlighting the emerging HRM models and future challenges for research, policy and practice. This text is invaluable reading for academics, students and practitioners alike.

Efficient management of health centres human resources in Zambia

This study uses Data Envelopment Analysis (DEA) to estimate the degree of technical, allocative and cost efficiency in individual public and private health centres in Zambia; and to identify the relative inefficiencies in the use of various inputs among individual health centers. About 83% of the 40 health centres were technically inefficient; and 88% of them were both allocatively and cost inefficient. The privately owned health centers were found to be more efficient than public facilities. © 2006 Springer Science+Business Media, Inc.

Role of organizational identification, on Implicit Leadership Theories ILTs, transformational leadership and work attitudes

This investigation explores the effects of organizational identification on employees’ Implicit Leadership Theories (ILTs) and the perception of leader behaviors. The study involved a cross-sectional survey of 439 employees from seven companies based in South Wales. Respondents completed two questionnaires that measured their organizational identification, ILTs, recognition of ILTs in their manager, manager’s leadership behaviors (transactional and transformational), and psychological reactions (job satisfaction, well-being, and turnover intentions). The level of organizational identification did not affect the prototype of an ideal work-based leader. However, high organizational identification was associated with more positive ratings on the actual manager, the extent to which their manager displayed transactional and transformational behaviors, and with more positive psychological reactions to work. Employees high in organizational identification based their judgments of their leader’s transactional and transformational behaviors on the extent to which they recognized their leader as possessing leadership traits. However, those low on organizational identification allowed their prototype of their ideal leader to bias their judgment of their actual leader’s behavior. Finally, there was partial support for the augmenting hypothesis (that tranformational leadership would predict additional variance in psychological outcomes above that predicted by transactional leadership) for those high in organizational identification but not for those low in organizational identification.