Gene-expression profiling reveals distinct expression patterns for classic versus variant Merkel cell phenotypes and new classifier genes to distinguish Merkel cell from small-cell lung carcinoma

Merkel cell carcinoma (MCC) is a rare aggressive skin tumor which shares histopathological and genetic features with small-cell lung carcinoma (SCLC), both are of neuroendocrine origin. Comparable to SCLC, MCC cell lines are classified into two different biochemical subgroups designated as 'Classic' and 'Variant'. With the aim to identify typical gene-expression signatures associated with these phenotypically different MCC cell lines subgroups and to search for differentially expressed genes between MCC and SCLC, we used cDNA arrays to pro. le 10 MCC cell lines and four SCLC cell lines. Using significance analysis of microarrays, we defined a set of 76 differentially expressed genes that allowed unequivocal identification of Classic and Variant MCC subgroups. We assume that the differential expression levels of some of these genes reflect, analogous to SCLC, the different biological and clinical properties of Classic and Variant MCC phenotypes. Therefore, they may serve as useful prognostic markers and potential targets for the development of new therapeutic interventions specific for each subgroup. Moreover, our analysis identified 17 powerful classifier genes capable of discriminating MCC from SCLC. Real-time quantitative RT-PCR analysis of these genes on 26 additional MCC and SCLC samples confirmed their diagnostic classification potential, opening opportunities for new investigations into these aggressive cancers.

Australian and New Zealand practice in intensive care (ANZPIC II: The spectrum of practice in the diagnosis and management of pneumonia in patients requiring mechanical ventilation

This study of ventilated patients investigated current clinical practice in 476 episodes of pneumonia (48% community-acquired pneumonia, 24% hospital-acquired pneumonia, 28% ventilator-associated pneumonia) using a prospective survey in 14 intensive care units (ICUs) within Australia and New Zealand. Diagnostic methods and confidence, disease severity, microbiology and antibiotic use were assessed. All pneumonia types had similar mortality (community-acquired pneumonia 33%, hospital-acquired pneumonia 37% and ventilator-associated pneumonia 24%, P = 0.15) with no inter-hospital differences (P = 0.08-0.91). Bronchoscopy was performed in 26%, its use predicted by admission hospital (one tertiary: OR 9.98, CI 95% 5.11-19.49, P < 0.001; one regional: OR 629, CI 95% 3.24-12.20, P < 0.001), clinical signs of consolidation (OR 3.72, CI 95% 2.09-662, P < 0.001) and diagnostic confidence (OR 2.19, CI 95% 1.29-3.72, P = 0.004). Bronchoscopy did not predict outcome (P = 0.11) or appropriate antibiotic selection (P = 0.69). Inappropriate antibiotic prescription was similar for all pneumonia types (11-13%, P = 0.12) and hospitals (0-16%, P = 0.25). Blood cultures were taken in 51% of cases. For community-acquired pneumonia, 70% received a third generation cephalosporin and 65% a macrolide. Third generation cephalosporins were less frequently used for mild infections (OR 0.38, CI 95% 0.16-0.90, P = 0.03), hospital-acquired pneumonia (OR 0.40, CI 95% 0.23-0.72, P < 0.01), ventilator-associated pneumonia (OR 0.04, CI 95% 0.02-0.13, P < 0.001), suspected aspiration (OR 0.20, CI 95% 0.04-0.92, P = 0.04), in one regional (OR 0.26, CI 95% 0.07-0.97, P = 0.05) and one tertiary hospital (OR 0.14, CI 95% 0.03-0.73, P = 0.02) but were more commonly used in older patients (OR 1.02, CI 95% 1.01-1.03, P = 0.01). There is practice variability in bronchoscopy and antibiotic use for pneumonia in Australian and New Zealand ICUs without significant impact on patient outcome, as the prevalence of inappropriate antibiotic prescription is low. There are opportunities for improving microbiological diagnostic work-up for isolation of aetiological pathogens.

Injuries associated with continuous miners, shuttle cars, load-haul-dump and personnel transport in New South Wales underground coal mines

In the three years to June 2005, 959 injuries associated with continuous miners (CMs), shuttle cars (SCs), load–haul–dump and personnel transport (PT) were reported by NSW underground coal mines, comprising 23% of all injuries reported. The present paper reports an analysis of the narrative field accompanying these reports to determine opportunities for controlling injury risks. The most common combinations of activity and mechanism were: strain while handling CM cable (96 injuries); caught between or struck by moving parts while bolting on a CM (86 injuries); strains while bolting on CM (54 injuries); and slipping off a CM during access, egress or other activity (60 injuries). For the other equipment considered, the common injury mechanism was the vehicle running over a pothole or other roadway abnormality causing the driver or passengers to be injured (169 injuries). Potential control measures include: monorails for CM services; hydraulic cable reelers; handrails on CM platforms; redesign of CM platforms and bolting rigs to reduce reach distances during drilling and bolting; improvements to guarding of bolting controls; standardisation and shape coding of bolting controls; two handed fast feed; improvements in underground roadway maintenance, vehicle suspension, visibility and seating; and pedestrian proximity warning devices.

The judicious utilization of new technologies through authentic learning in higher education: A case study

Though technology holds significant promise for enhanced teaching and learning it is unlikely to meet this promise without a principled approach to course design. There is burgeoning discourse about the use of technological tools and models in higher education, but much of the discussion is fixed upon distance learning or technology based courses. This paper will develop and propose a balanced model for effective teaching and learning for “on campus” higher education, with particular emphasis on the opportunities for revitalisation available through the judicious utilisation of new technologies. It will explore the opportunities available for the creation of more authentic learning environments through the principled design. Finally it will demonstrate with a case study how these have come together enabling the creation of an effective and authentic learning environment for one pre-service teacher education course at the University of Queensland.

Water, Communities and Mineral Resource Development: Understanding the Risks and Opportunities

Issues around water – its quality, use, availability and environmental value – can be a major point of tension between mineral projects and local communities. Failure to manage these issues appropriately can jeopardise the obtaining of regulatory approvals for new projects and place at risk the ‘social licence to operate’ of existing operations. Conversely, there may also be significant opportunities for companies to engage constructively with communities over water issues and to make a positive contribution to the sustainable development of these communities. Using case studies, this paper will explore the various types of social risks and opportunities associated with water and mineral resource development and identify key learnings relating to the management of these issues.

A new breed of doctor? Lessons learned and changes made to library services for the MBBS program at the University of Queensland

November 2000 saw the graduation of the first cohort from the new MBBS Program at The University of Queensland. The fully integrated problem-based curriculum has provided many challenges and opportunities for The University of Queensland Library such as servicing an extensive remote student population, information technology issues and customer demand. In October 2000 all four years of the MBBS Program completed a survey on related issues such as the library's collection, web-based resources, information skills and evidence-based medicine. This paper focuses on the results of the survey, and the future directions of the library to ensure that the new doctors graduating from this program gain the essential attributes of life-long learning, information management and evidence-based principles.

The politics of the new Germany

The Politics of the New Germany takes a new approach to understanding politics in the post-unification Federal Republic. Assuming only elementary knowledge, it focuses on debates and issues in order to help students understand both the workings of Germany's key institutions and some of the key policy challenges facing German politicians. Written in a straightforward style by four experts, each of the chapters draws on a rich variety of real-world examples. Packed with boxed summaries of key points, a guide to further reading and a range of seminar questions for discussion at the end of each chapter, this book highlights both the challenges and opportunities facing policy-makers in such areas as foreign affairs, economic policy, immigration, identity politics and institutional reforms. The book also takes a bird's-eye view of the big debates that define German politics over time, regardless of which party happens to be in power. It pinpoints three key themes that have characterised German politics over the last sixty years; reconciliation, consensus and transformation. Table of Contents: Introduction 1. Germany and the Burden of History 2. Germany’s Post-War Development, 1945-1989 3. Towards German Unity? 4. A Blockaded System of Government? 5. The Party System and Electoral Behaviour: The Path to Stable Instability? 6. Economic Management: The End of the German Model? 7. Citizenship and Demographics: A Country of Immigration? 8. The Reform of the Welfare State? 9. Germany and the European Union: A European Germany or a German Europe? 10. Foreign and Security Policy: A New Role for the Twenty-First Century? 11. Conclusion

Strategies and therapeutic opportunities for the delivery of drugs to the esophagus

Targeting of drugs and therapies locally to the esophagus is an important objective in the development of new and more effective dosage forms. Therapies that are retained within the oral cavity for both local and systemic action have been utilized for many years, although delivery to the esophagus has been far less reported. Esophageal disease states, including infections, motility disorders, gastric reflux, and cancers, would all benefit from localized drug delivery. Therefore, research in this area provides significant opportunities. The key limitation to effective drug delivery within the esophagus is sufficient retention at this site coupled with activity profiles to correspond with these retention times; therefore, a suitable formulation needs to provide the drug in a ready-to-work form at the site of action during the rapid transit through this organ. A successfully designed esophageal-targeted system can overcome these obstacles. This review presents a range of dosage form approaches for targeting the esophagus, including bioadhesive liquids and orally retained lozenges, chewing gums, gels, and films, as well as endoscopically delivered therapeutics. The techniques used to measure efficacy both in vitro and in vivo are also discussed. Drug delivery is a growing driver within the pharmaceutical industry and offers benefits both in terms of clinical efficacy, as well as in market positioning, as a means of extending a drug's exclusivity and profitability. Emerging systems that can be used to target the esophagus are reported within this review, as well as the potential of alternative formulations that offer benefits in this exciting area.

Women in management in the new economic environment:the case of India

Liberalization of the Indian economy has created considerable employment opportunities for those, including women, who possess marketable skills and talent. Historically, women in India have not enjoyed a good status in workplace settings whether in managerial or operative roles. This traditional positioning of women has restricted the intensity of their efforts towards realizing the benefits of the globalisation process. An attempt has been made in this contribution to highlight the important issues relating to women in management in the Indian context. The messages from a review of the literature are analysed. Research evidence from various sources is presented to highlight the dynamics of developments in the status of Indian women managers. The contribution discusses the main aspects of the historical, socio-cultural and economic factors influencing women managers: issues concerning gender-based stereotypes; the main barriers to women's movement to top managerial positions; the impact of developments in information technology (IT) on women managers; and the way forward. Results from two research projects are also presented. The analysis has important messages for practitioners and contributes to women's studies and management in the Indian context. © 2005 Taylor & Francis Ltd.

Technology transfer and Chinese government policy:opportunities and implications for business

State-owned enterprises in China have been given greater autonomy and responsibility, have freer access to foreign technology, and are being encouraged to form groups to gain from rationalization and integration. This article uses case studies to identify the key strategic issues that affect the commercial viability of foreign technology acquisition by state-owned enterprises within the context of enterprise reforms. All the case study enterprises used technology transfer to develop new or improved products. Technologies acquired as parts of subcontracting arrangements and well-established technologies to produce end-use products are easier to manage and operate profitably. However, the latter type of technology has been imported by numerous enterprises and has led to fierce competition and industy restructuring. Importing capital-intensive and complex technology to produce major components for products, such as cars, is more difficult and requires closer coordination with customers and suppliers.

The politics of the new Germany

The Politics of the New Germany continues to provide the most comprehensive, authoritative and up-to-date textbook on contemporary German Politics. The text takes a new approach to understanding politics in the post-unification Federal Republic. Assuming only elementary knowledge, it focuses on a series of the most important debates and issues in Germany today with the aim of helping students understand both the workings of the country's key institutions and some of the most important policy challenges facing German politicians. For this second edition, the content has been comprehensively updated throughout, augmented by additional factboxes and data, and features new material on: •Grand coalition •Lisbon treaty •Constitutional court •Financial crisis •Reform of social policy •Afghanistan. Written in a straightforward style by three experts, each of the chapters draws on a rich variety of real-world examples. In doing so, it highlights both the challenges and opportunities facing policy-makers in such areas as foreign affairs, economic policy, immigration, identity politics and institutional reform. The book also takes a bird’s-eye view of the big debates that have defined German politics over time, regardless of which political parties happened to be in power. It pinpoints three key themes that have characterised German politics over the last sixty years; reconciliation, consensus and transformation. The book is a comprehensive, yet highly accessible, overview of politics in 21st Century Germany and should be essential reading for students of politics and international relations, as well as of European and German studies.

Green as the new Lean:how to use Lean practices as a catalyst to greening your supply chain

The aim of this research paper is to explore and evaluate previous work focussing on the relationship and links between Lean and Green supply chain management practices. Several explanatory frameworks are explored and discussed. It is intended that evidence and insights can be developed and used: (a) to assist our understanding of where Lean practices are synergistic for Green; (b) to clarify if Green practices are synergistic for Lean; and (c) to identify opportunities for companies to use their Lean framework as a catalyst to making their processes Green. The paper provides evidence suggesting that Lean is beneficial for Green practices and the implementation of Green practices in turn also has a positive influence on existing Lean business practices. © 2010 Elsevier Ltd. All rights reserved.

The finance of biotechnology:investment in new biotechnology firms by British venture capitalists-attitudes to, and evaluation of, business proposals

A notable feature of the recent commercialisation of biotechnology has been the success of 200 or so new firms, established in America since 1976, in exploiting specialised market niches. A key factor in their formation has been the ready availability of venture capital funding. These firms have been instrumental in establishing America's lead in exploiting biotechnology. It is this example which Britain has attempted to emulate as part of its strategy for developing its own biotechnology capabilities. This thesis investigated some aspects of the relationship between biotechnology and venture capital, concentrating on the determinants of the venture capitalist's investment decision. Following an extensive literature survey, two hypothetical business proposals were used to find what venture capitalists themselves consider to be the key elements of this decision. It was found that venture capitalists invest in people, not products, and businesses, not industries. It was concluded that venture capital-backed small firms should, therefore, be seen as an adjunct to the development of biotechnology in Britain, rather than as a substitute for a co-ordinated, co-operative strategy involving Government, the financial institutions, industry and academia. This is chiefly because the small size of the UK's domestic market means that many potentially important innovations in biotechnology may continue to be lost, since the short term identification of market opportunities for biotechnology products will dictate that they are insupportable in Britain alone. In addition, the data analysis highlighted some interesting methodological issues concerning the investigation of investment decision making. These related especially to shortcomings in the use of scoresheets and questionnaires in research in this area. The conclusion here was that future research should concentrate on the reasons why an individual reaches an investment decision. It is argued that only in this way can the nature of the evaluation procedures employed by venture capitalists be properly understood.

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.

Industrial new product planning:a study of the sources of new product ideas and the development of new product proposals in the UK computer industry

This thesis presents a study of the sources of new product ideas and the development of new product proposals in an organisation in the UK Computer Industry. The thesis extends the work of von Hippel by showing how the phenomenon which he describes as "the Customer Active Paradigm for new product idea generation" can be observed to operate in this Industry. Furthermore, this thesis contrasts his Customer Active Paradigm with the more usually encountered Manufacturer Active Paradigm. In a second area, the thesis draws a number of conclusions relating to methods of market research, confirming existing observations and demonstrating the suitability of flexible interview strategies in certain circumstances. The thesis goes on to demonstrate the importance of free information flow within the organisation, making it more likely that sought and unsought opportunities can be exploited. It is shown that formal information flows and documents are a necessary but not sufficient means of influencing the formation of the organisation's dominant ideas on new product areas. The findings also link the work of Tushman and Katz on the role of "Gatekeepers" with the work of von Hippel by showing that the role of gatekeeper is particularly appropriate and useful to an organisation changing from Customer Active to Manufacturer Active methods of idea generation. Finally, the thesis provides conclusions relating to the exploitation of specific new product opportunities facing the sponsoring organisation.