Mathematical modeling of the cancer cell’s control circuitry : paving the way to individualized therapeutic strategies

Cancer is a disease of signal transduction in which the dysregulation of the network of intracellular and extracellular signaling cascades is sufficient to thwart the cells finely-tuned biochemical control mechanisms. A keen interest in the mathematical modeling of cell signaling networks and the regulation of signal transduction has emerged in recent years, and has produced a glimmer of insight into the sophisticated feedback control and network regulation operating within cells. In this review, we present an overview of published theoretical studies on the control aspects of signal transduction, emphasizing the role and importance of mechanisms such as ‘ultrasensitivity’ and feedback loops. We emphasize that these exquisite and often subtle control strategies represent the key to orchestrating ‘simple’ signaling behaviors within the complex intracellular network, while regulating the trade-off between sensitivity and robustness to internal and external perturbations. Through a consideration of these apparent paradoxes, we explore how the basic homeostasis of the intracellular signaling network, in the face of carcinogenesis, can lead to neoplastic progression rather than cell death. A simple mathematical model is presented, furnishing a vivid illustration of how ‘control-oriented’ models of the deranged signaling networks in cancer cells may enucleate improved treatment strategies, including patient-tailored combination therapies, with the potential for reduced toxicity and more robust and potent antitumor activity.

The role of intellectual resources, product innovation capability, reputational resources and marketing capability combinations in SME growth

This article examines the extent to which combinations of intellectual resources and product innovation capability, and reputational resources and marketing capability, influence the ability of small and medium-sized enterprises (SME) to meet or exceed performance goals. Empirical results drawn from 171 SMEs suggest that when the combination of intellectual resources and product innovation capability in addition to the combination of reputational resources and marketing capability are high, SME growth is enhanced. However, a high level of intellectual resources combined with a low level of product innovation capability as well as a combination of a high level of reputational resources with a low level of marketing capability (and vice versa) are not significantly related to growth. These results imply that a high level of resources cannot compensate for a low level of capabilities (and vice versa).

The rule of law, the public interest and the management of natural resources in Australia

The statutory arrangements for the management of natural resources in Australia confer powers of decision-making upon government agencies and, at the same time, restrict how these powers are to be exercised by reference either to stated criteria or in some instances to the public interest. These restrictions perform different functions according to their structure, form and language: for example they may be in the form of jurisdictional, deliberative or purposive rules. This article reviews how the offshore resources legislation of the Commonwealth and some examples of the onshore resources legislation of Queensland address the functions performed by the public interest in determining whether there is compliance with the principle of the rule of law.

Delivery of therapeutic molecules using electrosprayed polymeric particles for applications in tissue engineering

This thesis has developed an innovative technology, electrospraying, that allows biodegradable microparticles to deliver pharmaceuticals that aid bone regeneration. The establishment, characterisation and optimisation of the technique are a step forward in developing an affordable and safe alternative to the products used currently in the clinical setting for the treatment of musculoskeletal disorders. The researcher has also investigated electrospraying as a coating technique on biodegradable structures that are used to replace damaged tissues, in order to provide localised and efficient drug delivery in the site of the defect to help tissue reconstruction.

Technology, Natural Resources and Economic Growth: Improving the Environment for a Greener Future

Description Through a combination of global data analysis and focused country level analysis, this timely book provides answers to the most pertinent country and industry specific questions defining the current relationship between technology, natural resources and economic growth. Contents Contents: Preface Part I: Global Analysis 1. Economic Growth and the Environment 2. Energy Substitution and Carbon Dioxide Emissions 3. Pollution, Natural Resources, and Economic Growth 4. Trade Openness and Environmental Quality 5. Environmental Productivity 6. Energy Price-induced Technological Change 7. Trade-induced Technological Change 8. Regional Economic Integration Part II: Country-Level Analysis 9. Emissions Trading in the United States 10. Increasing Returns to Pollution Abatement in the United States 11. Policy-induced Competitiveness in the United States 12. Trade Liberalization, Technology, and the Environment 13. Policy Implementation and its Effectiveness in China 14. Clean Technological Inventions in Japan 15. Intervention of Economic Policy and its Nonlinear Effects in Japan 16. The Next Emerging Giants: India and Africa 17. Conclusion Index Further information Through a combination of global data analysis and focused country level analysis, this timely book provides answers to the most pertinent country and industry specific questions defining the current relationship between technology, natural resources and economic growth. Shunsuke Managi takes a distinctive approach by focusing on the design and implementation of environmental regulations that encourage technological progress and, in doing so, looks at ways to ensure productivity improvements in the face of increasingly stringent environmental regulations and natural resource depletion. The findings in this important book demonstrate how successful environmental policies can contribute to efficiency by encouraging, rather than inhibiting, technological innovation. Technology, Natural Resources and Economic Growth will provide a valuable resource for a wide readership including postgraduate students, researchers, academics and policy makers working in the fields of environmental and ecological economics.

Tetraspanins as regulators of the tumour microenvironment : implications for metastasis and therapeutic strategies

One of the hallmarks of cancer is the ability to activate invasion and metastasis (Hanahan et al., 2011). Cancer morbidity and mortality are largely related to the spread of the primary, localised tumour to adjacent and distant sites (Pantel et al., 2004). Appropriate management and treatment decisions of predicting metastatic disease at the time of diagnosis is thus crucial, which supports better understanding of the metastatic process. There are common events that occur during metastasis: dissociation from the primary tumour mass, reorganisation/remodelling of extracellular matrix, cell migration, recognition and transversal of endothelial cells and the vascular circulation and lodgement and proliferation within ectopic stroma (Wells, 2006). One of the key and initial events is the increased capability of cancer cells to move, escaping the regulation of normal physiological control. The cellular cytoskeleton plays an important role in cancer cell motility and active cytoskeletal rearrangement can result in metastatic disease. This active change in cytoskeletal dynamics results in manipulation of plasma membrane and cellular balance between cellular adhesion and motility which in turn determines cancer cell movement. Members of the tetraspanins play important roles in regulation of cancer migration and cancer-endothelial cell interactions, which are critical for cancer invasion and metastasis. Their involvements in active cytoskeletal dynamics, cancer metastasis and potential clinical application will be discussed in this review. In particular, tetraspanin member, CD151, is highlighted for its major role in cancer invasion and metastasis

Development of a new regulatory model for occupational health and safety in the New South Wales coal industry: an issues paper for the New South Wales Department of Mineral Resources

This paper addresses the regulatory issues arising in developing a new regulatory model for the New South Wales Coal Industry. As such, it identifies the relevant literature on this subject, the options available for reform, and the experience of Australian and key international bodies responsible for the development of regulatory standards in this area. In particular it: Identifies the main shortcomings in the existing regulatory approach; Identifies the potential roles/main strengths and weaknesses of different types of standards (eg specification, performance, process and systems-based rules) and potential “best practice’ combinations of standards; Examines the appropriateness of the current regulatory regime whereby the general OHS legislation (including the general duty provisions) applies to mining in addition to the large body of regulation which is specific to mining; Identifies the importance of, and possible means of addressing, issues of worker participation within the coal mining industry; Draws on the literature on what motivates companies and individuals for the purpose of recommending key provisions for inclusion in new legislation to provide appropriate personal and organisational incentives; Draws on the literature on major hazards facilities to suggest the appropriate roles for OHS management systems and safety reports or comparable approaches (eg mine safety management plans); Draws on the United Kingdom (UK) and United States of America (USA) experience of coal mine safety and its regulation for comparative purposes, and for insights as to what sort of regulation most effectively reduces work related injury and disease in coal mining; Examines the relevant roles of International Labour Organisation (ILO) Conventions; Examines the extent to which different regulatory regimes would be appropriate to open cut and underground coal mining; and Examines options for reform. This paper is focussed specifically on the issues identified above.

Functions and therapeutic roles of exosomes in cancer

The role of exosomes in cancer development has become the focus of much research, due to the many emerging roles possessed by exosomes. These micro-vesicles that are ubiquitously released in to the extracellular milieu, have been found to regulate immune system function, particularly in tumorigenesis, as well as conditioning future metastatic sites for the attachment and growth of tumor tissue. Through an interaction with a range of host tissue, exosomes are able to generate a pro-tumor environment that is essential for carcinogenesis. Herein, we discuss the contents of exosomes and their contribution to tumorigenesis, as well as their role in chemotherapeutic resistance and the development of novel cancer treatments and the identification of cancer biomarkers.

Social Justice Impacts of the Resources Boom

Until the 1970s mining leases were issued by state governments subject to conditions that companies build or substantially finance local community infrastructure, including housing, streets, transport, schools, hospitals and recreation facilities. Townships and communities went hand in hand with mining development. However, in the past thirty years mining companies have moved progressively to an expeditionary strategy for natural resources extraction - operating a continuous production cycle of 12 hour shifts - increasingly reliant on non-resident, fly-in, fly-out or drive-in, drive-out (FIFO/DIDO) workers who typically work block rosters, reside in work camps adjacent to existing communities and travel large distances from their homes. This paper presents the key findings of our survey into the social impacts of this kind of mining development in Qld. Based on the results we argue that the social license to develop new mining projects is strong for projects requiring a 25% or less non-resident workforce, diminishes significantly thereafter and is very weak for projects planning to recruit a non-resident workforce in excess of 75%. This finding is significant because there are at least 67 new mining projects undergoing social impact assessment in Queensland, and many it appears are planning to hire significant proportions of non-resident workers. The paper considers the policy implications of this growing social justice issue concluding there is a clear need for national leadership in formulating a national policy framework for guiding socially responsible and sustainable mining development into the next millennium.

Antimicrobial stewardship activities : a survey of Queensland hospitals

Objective: In 2011, the Australian Commission on Safety and Quality in Health Care (ACSQHC) recommended that all hospitals in Australia must have an Antimicrobial Stewardship (AMS) program by 2013. Nevertheless, little is known about current AMS activities. This study aimed to determine the AMS activities currently undertaken, and to identify gaps, barriers to implementation and opportunities for improvement in Queensland hospitals. Methods: The AMS activities of 26 facilities from 15 hospital and health services in Queensland were surveyed during June 2012 to address strategies for effective AMS: implementing clinical guidelines, formulary restriction, reviewing antimicrobial prescribing, auditing antimicrobial use and selective reporting of susceptibility results. Results: The response rate was 62%. Nineteen percent had an AMS team (a dedicated multidisciplinary team consisting of a medically trained staff member and a pharmacist). All facilities had access to an electronic version of Therapeutic Guidelines: Antibiotic, with a further 50% developing local guidelines for antimicrobials. One-third of facilities had additional restrictions. Eighty-eight percent had advice for restricted antimicrobials from in-house infectious disease physicians or clinical microbiologists. Antimicrobials were monitored with feedback given to prescribers at point of care by 76% of facilities. Deficiencies reported as barriers to establishing AMS programs included: pharmacy resources, financial support by hospital management, and training and education in antimicrobial use. Conclusions: Several areas for improvement were identified: reviewing antimicrobial prescribing with feedback to the prescriber, auditing, and training and education in antimicrobial use. There also appears to be a lack of resources to support AMS programs in some facilities. What is known about the topic? The ACSQHC has recommended that all hospitals implement an AMS program by 2013 as a requirement of Standard 3 (Preventing and Controlling Healthcare-Associated Infections) of the National Safety and Quality Health Service Standards. The intent of AMS is to ensure appropriate prescribing of antimicrobials as part of the broader systems within a health service organisation to prevent and manage healthcare-associated infections, and improve patient safety and quality of care. This criterion also aligns closely with Standard 4: Medication Safety. Despite this recommendation, little is known about what AMS activities are undertaken in these facilities and what additional resources would be required in order to meet these national standards. What does the paper add? This is the first survey that has been conducted of public hospital and health services in Queensland, a large decentralised state in Australia. This paper describes what AMS activities are currently being undertaken, identifies practice gaps, barriers to implementation and opportunities for improvement in Queensland hospitals. What are the implications for practitioners? Several areas for improvement such as reviewing antimicrobial prescribing with feedback to the prescriber, auditing, and training and education in antimicrobial use have been identified. In addition, there appears to be a lack of resources to support AMS programs in some facilities.

Emotional intelligence and job-demands resources model

Occupational stress research has consistently demonstrated negative effects for employees. Research also describes potential moderators of this relationship. While research has revealed some positive effects of emotional intelligence (EI) on employee adjustment, it has neglected investigation of their potential stress buffering effects. Based on the Job-Demand Resources model, it was predicted that higher trait emotional intelligence would act as a buffer to the potential negative effects of stressors on employee adjustment. Hierarchical multiple regression analyses with a sample of 306 nurses found no main effects of EI but revealed eight moderating effects. While some interactions support the buffering hypothesis, others revealed buffering for those with low EI. Findings are discussed in terms of theoretical and practical implications.

The flip side of fly-in-fly-out : the use of 457 visas by smaller firms in the Western Australian resources sector

The focus in this article is how the extensive use of fly-in fly-out (FIFO) working arrangements in the Western Australian resources sector has an impact directly and indirectly on smaller firms and their ability to recruit workers in remote locations. We argue that the growth of FIFO working arrangements has disadvantaged smaller resource-sector firms by increasing their employment costs and decreasing their ability to attract skilled workers. As a result, smaller resource-sector firms are recruiting skilled workers on 457 visas to secure their business stability and growth, despite the complexity, costs, and risks involved.

Multilingual lexical resources to detect cognates in non-aligned texts

The identification of cognates between two distinct languages has recently start- ed to attract the attention of NLP re- search, but there has been little research into using semantic evidence to detect cognates. The approach presented in this paper aims to detect English-French cog- nates within monolingual texts (texts that are not accompanied by aligned translat- ed equivalents), by integrating word shape similarity approaches with word sense disambiguation techniques in order to account for context. Our implementa- tion is based on BabelNet, a semantic network that incorporates a multilingual encyclopedic dictionary. Our approach is evaluated on two manually annotated da- tasets. The first one shows that across different types of natural text, our method can identify the cognates with an overall accuracy of 80%. The second one, con- sisting of control sentences with semi- cognates acting as either true cognates or false friends, shows that our method can identify 80% of semi-cognates acting as cognates but also identifies 75% of the semi-cognates acting as false friends.