Precautionary principles: a jurisdiction-free framework for decision-making under risk

Fundamental principles of precaution are legal maxims that ask for preventive actions, perhaps as contingent interim measures while relevant information about causality and harm remains unavailable, to minimize the societal impact of potentially severe or irreversible outcomes. Such principles do not explain how to make choices or how to identify what is protective when incomplete and inconsistent scientific evidence of causation characterizes the potential hazards. Rather, they entrust lower jurisdictions, such as agencies or authorities, to make current decisions while recognizing that future information can contradict the scientific basis that supported the initial decision. After reviewing and synthesizing national and international legal aspects of precautionary principles, this paper addresses the key question: How can society manage potentially severe, irreversible or serious environmental outcomes when variability, uncertainty, and limited causal knowledge characterize their decision-making? A decision-analytic solution is outlined that focuses on risky decisions and accounts for prior states of information and scientific beliefs that can be updated as subsequent information becomes available. As a practical and established approach to causal reasoning and decision-making under risk, inherent to precautionary decision-making, these (Bayesian) methods help decision-makers and stakeholders because they formally account for probabilistic outcomes, new information, and are consistent and replicable. Rational choice of an action from among various alternatives-defined as a choice that makes preferred consequences more likely-requires accounting for costs, benefits and the change in risks associated with each candidate action. Decisions under any form of the precautionary principle reviewed must account for the contingent nature of scientific information, creating a link to the decision-analytic principle of expected value of information (VOI), to show the relevance of new information, relative to the initial ( and smaller) set of data on which the decision was based. We exemplify this seemingly simple situation using risk management of BSE. As an integral aspect of causal analysis under risk, the methods developed in this paper permit the addition of non-linear, hormetic dose-response models to the current set of regulatory defaults such as the linear, non-threshold models. This increase in the number of defaults is an important improvement because most of the variants of the precautionary principle require cost-benefit balancing. Specifically, increasing the set of causal defaults accounts for beneficial effects at very low doses. We also show and conclude that quantitative risk assessment dominates qualitative risk assessment, supporting the extension of the set of default causal models.

Pleomorphic lobular carcinoma of the breast: role of comprehensive molecular pathology in characterization of an entity

Immunohistochemical analysis of E-cadherin has changed the way lobular neoplasia is perceived. It has helped to classify difficult cases of carcinoma in situ with indeterminate features and led to the identification of new variants of lobular carcinoma. Pleomorphic lobular carcinoma (PLC) and pleomorphic lobular carcinoma in situ (PLCIS), recently described variants of invasive and in situ classic lobular carcinoma, are reported to be associated with more aggressive clinical behaviour. Although PLC/PLCIS show morphological features of classic lobular neoplasia and lack E-cadherin expression, it is still unclear whether these lesions evolve through the same genetic pathway as lobular carcinomas or are high-grade ductal neoplasms that have lost E-cadherin. Here we have analysed a case of extensive PLCIS and invasive PLC associated with areas of E-cadherin-negative carcinoma in situ with indeterminate features, using immunohistochemistry, chromogenic in situ hybridization, high-resolution comparative genomic hybridization (CGH) and array-based CGH. We observed that all lesions lacked E-cadherin and beta-catenin and showed gain of 1q and loss of 16q, features that are typical of lobular carcinomas but are not seen in high-grade ductal lesions. In addition, amplifications of c-myc and HER2 were detected in the pleomorphic components, which may account for the high-grade features in this case and the reported aggressive clinical behaviour of these lesions. Taken together, these data suggest that at least some PLCs may evolve from the same precursor or through the same genetic pathway as classic lobular carcinomas. Copyright (c) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Multi-level zero-inflated Poisson regression modelling of correlated count data with excess zeros

Count data with excess zeros relative to a Poisson distribution are common in many biomedical applications. A popular approach to the analysis of such data is to use a zero-inflated Poisson (ZIP) regression model. Often, because of the hierarchical Study design or the data collection procedure, zero-inflation and lack of independence may occur simultaneously, which tender the standard ZIP model inadequate. To account for the preponderance of zero counts and the inherent correlation of observations, a class of multi-level ZIP regression model with random effects is presented. Model fitting is facilitated using an expectation-maximization algorithm, whereas variance components are estimated via residual maximum likelihood estimating equations. A score test for zero-inflation is also presented. The multi-level ZIP model is then generalized to cope with a more complex correlation structure. Application to the analysis of correlated count data from a longitudinal infant feeding study illustrates the usefulness of the approach.

Science-policy in environmental and health risk assessment: if we cannot do without, can we do better?

How can empirical evidence of adverse effects from exposure to noxious agents, which is often incomplete and uncertain, be used most appropriately to protect human health? We examine several important questions on the best uses of empirical evidence in regulatory risk management decision-making raised by the US Environmental Protection Agency (EPA)'s science-policy concerning uncertainty and variability in human health risk assessment. In our view, the US EPA (and other agencies that have adopted similar views of risk management) can often improve decision-making by decreasing reliance on default values and assumptions, particularly when causation is uncertain. This can be achieved by more fully exploiting decision-theoretic methods and criteria that explicitly account for uncertain, possibly conflicting scientific beliefs and that can be fully studied by advocates and adversaries of a policy choice, in administrative decision-making involving risk assessment. The substitution of decision-theoretic frameworks for default assumption-driven policies also allows stakeholder attitudes toward risk to be incorporated into policy debates, so that the public and risk managers can more explicitly identify the roles of risk-aversion or other attitudes toward risk and uncertainty in policy recommendations. Decision theory provides a sound scientific way explicitly to account for new knowledge and its effects on eventual policy choices. Although these improvements can complicate regulatory analyses, simplifying default assumptions can create substantial costs to society and can prematurely cut off consideration of new scientific insights (e.g., possible beneficial health effects from exposure to sufficiently low 'hormetic' doses of some agents). In many cases, the administrative burden of applying decision-analytic methods is likely to be more than offset by improved effectiveness of regulations in achieving desired goals. Because many foreign jurisdictions adopt US EPA reasoning and methods of risk analysis, it may be especially valuable to incorporate decision-theoretic principles that transcend local differences among jurisdictions.

Population mobility and indigenous peoples in Australasia and North America

This book draws together relevant research findings to produce the first comprehensive overview of Indigenous peoples' mobility. Chapters draw from a range of disciplinary sources, and from a diversity of regions and nation-states. Within nations, mobility is the key determinant of local population change, with implications for service delivery, needs assessment, and governance. Mobility also provides a key indicator of social and economic transformation. As such, it informs both social theory and policy debate. For much of the twentieth century conventional wisdom anticipated the steady convergence of socio-demographic trends, seeing this as an inevitable concomitant of the development process. However, the patterns and trends in population movement observed in this book suggest otherwise, and provide a forceful manifestation of changing race relations in these new world settings. © 2009 Informa plc

Adaptive Signal Processing for Power Line Communications

This thesis represents a significant part of the research activity conducted during the PhD program in Information Technologies, supported by Selta S.p.A, Cadeo, Italy, focused on the analysis and design of a Power Line Communications (PLC) system. In recent times the PLC technologies have been considered for integration in Smart Grids architectures, as they are used to exploit the existing power line infrastructure for information transmission purposes on low, medium and high voltage lines. The characterization of a reliable PLC system is a current object of research as well as it is the design of modems for communications over the power lines. In this thesis, the focus is on the analysis of a full-duplex PLC modem for communication over high-voltage lines, and, in particular, on the design of the echo canceller device and innovative channel coding schemes.

Role of fibroblast growth factor receptor in regulation of membrane traffic

Several studies show that membrane transport mechanisms are regulated by signalling molecules. Recently, genome-wide screen analyses in C.elegans have enabled scientists to identify novel regulators in membrane trafficking and also signalling molecules which are found to couple with this machinery. Fibroblast growth factor (FGF) via binding to fibroblast growth factor receptor (FGFR) mediate signals which are essential in the development of an organism, patterning, cell migration and tissue homeostasis. Impaired FGFR-mediated signalling has been associated with various developmental, neoplastic, metabolic and neurological diseases and cancer. In this study, the potential role of FGFR-mediated signalling pathway as a regulator of membrane trafficking was investigated. The GFP-tagged yolk protein YP170-GFP trafficking was analysed in worms where 1) FGFR signalling cascade components were depleted by RNAi and 2) in mutant animals. From these results, it was found that the disruption of the genes egl-15 (FGFR), egl-17(FGF), let-756(FGF), sem-5, let-60, lin-45, mek-2, mpk-1 and plc-3 lead to abnormal localization of YP170-GFP, suggesting that signalling downstream of FGFR via activation of MAPK and PLC-γ pathway is regulating membrane transport. The route of trafficking was further investigated, to pinpoint which membrane step is regulated by worm FGFR, by analysing a number of GFP-tagged intracellular membrane markers in the intestine of Wild Type (WT) and FGFR mutant worms. FGFR mutant worms showed a significant difference in the localisation of several endosomal membrane markers, suggesting its regulatory role in early and recycling steps of endocytosis. Finally, the trafficking of transferrin in a mammalian NIH/3T3 cell line was investigated to identify the conservation of these membrane trafficking regulatory mechanisms between organisms. Results showed no significant changes in transferrin trafficking upon FGFR stimulation or inhibition.

Casebook on contract law

This volume provides students with a comprehensive selection of the cases most likely to be encountered on contract law courses and is specifically designed to meet their needs. The case law is helpfully structured and presented under clear headings, with the emphasis on explaining the decisions and their implications in order to promote better understanding. The fifth edition incorporates important judgments and assesses the significance of recent decisions of the House of Lords such as Attorney-General v Blake and Alfred McAlpine Construction Ltd v Panatown Ltd and the decisions of the Court of Appeal in Director General of Fair Trading v First National Bank plc and Barclays Bank v Coleman. Important recent decisions on remedies for misrepresentation have also been included.

Casebook on contract law

The law of contract can be a complex and technical subject, rvt the new edition of Jill Poole's Casebook on Contract provides a clear and well-structured exposition of the principles and rules through a comprehensive selection of case law, addressing all aspects encountered on undergraduate courses. Opening with a chapter of valuable advice and guidance on how to successfully develop and improve the essential skills of case-reading, featuring two worked examples, the coverage in this sixth edition expands to incorporate all recent significant decisions and judgments made by the House of Lords and Court of Appeal such as, Director General of Fair Trading v First National Bank plc, Farley v Skinner, Royal Bank of Scotland v Etridge and UCB Corporate Services v Williams. Interesting recent decisions in relation to battle of forms, terms, exemption clauses and misrepresentation are also included. Extracts have been chosen from a wide range of historical and contemporary cases to illustrate the reasoning processes of the court, why decisions are made and how legal principles are developed - enabling cases to be analysed and discussed independently while, taken as a whole, the chapters provide a sound understanding of the modern law of contract. The section on damages for breach of contract has been expanded to reassess Ruxley Electronics and Construction Ltd v Forsyth in the light of Farley v Skinner, the future of Addis v Gramophone Co Ltd is considered in the light of Johnson v Unisys Ltd and Attorney General v Blake is examined in the light of the decision in Esso Petroleum Co Ltd v Niad Ltd. Succinct author comment focuses the reader on the key elements within the extracts, while thought-provoking questions are posed throughout to develop more in-depth analysis. The logical and clear organization of topics has been further improved to more accurately echo the order adopted within the author's popular textbook and closer crossreferencing to this text has been incorporated to highlight where more detailed discussion of issues arising from the caselaw can be explored. As a result, this new edition can be used both as a traditional casebook and as a companion volume to Poole's Textbook on Contract. This edition is also supported by a new companion web site that offers the benefits of essential updating of key materials, sample questions, lists for key further reading sources and relevant web links, additional relevant cases and materials and guidance on successful exam technique. As with previous editions, Casebook on Contract is an invaluable primary source and an essential study aid for all those following elements of contract law as part of the LLB and CPE, as well as for students from related disciplines such as Accounting and Business.

Justifying partial rescission in English law

Comments on the refusal of the English courts to recognise the existence of a remedy of partial rescission, suggesting that in certain restricted instances justification exists for the grant of such a remedy. Considers the nature of the remedy of rescission under English law, the English courts' approach towards partial rescission and the nature and scope of the discretions available to the courts, noting the decisions in TSB Bank Plc v Camfield and De Molestina v Ponton. Reviews the historical origins of the remedy of rescission, including the distinction between fraudulent and non fraudulent misrepresentation and the origins of the so called concurrent and auxiliary equitable jurisdictions. Compares the approach of the Australian courts and highlights examples of recognition of partial rescission under international law.

Signal transduction pathways involved in proteolysis-inducing factor induced proteasome expression in murine myotubes

The proteolysis-inducing factor (PIF) is produced by cachexia-inducing tumours and initiates protein catabolism in skeletal muscle. The potential signalling pathways linking the release of arachidonic acid (AA) from membrane phospholipids with increased expression of the ubiquitin-proteasome proteolytic pathway by PIF has been studied using C2C12 murine myotubes as a surrogate model of skeletal muscle. The induction of proteasome activity and protein degradation by PIF was blocked by quinacrine, a nonspecific phospholipase A2 (PLA2) inhibitor and trifluroacetyl AA, an inhibitor of cytosolic PLA2. PIF was shown to increase the expression of calcium-independent cytosolic PLA2, determined by Western blotting, at the same concentrations as those inducing maximal expression of 20S proteasome α-subunits and protein degradation. In addition, both U-73122, which inhibits agonist-induced phospholipase C (PLC) activation and D609, a specific inhibitor of phosphatidylcholine-specific PLC also inhibited PIF-induced proteasome activity. This suggests that both PLA 2 and PLC are involved in the release of AA in response to PIF, and that this is important in the induction of proteasome expression. The two tyrosine kinase inhibitors genistein and tryphostin A23 also attenuated PIF-induced proteasome expression, implicating tyrosine kinase in this process. PIF induced phosphorylation of p44/42 mitogen-activated protein kinase (MAPK) at the same concentrations as that inducing proteasome expression, and the effect was blocked by PD98059, an inhibitor of MAPK kinase, as was also the induction of proteasome expression, suggesting a role for MAPK activation in PIF-induced proteasome expression. © 2003 Cancer Research UK.

Landlord and tenant law

This second edition contains many new questions covering recent developments in the field of landlord and tenant law including Bruton v London and Quadrant Housing Trust, Hemmingway Securities Ltd v Dunraven Ltd, British Telecommunications plc v Sun Life Assurance Society plc and Graysim Holdings Ltd v P&O Property Holdings Ltd. New topics covered also include the Landlord and Tenant (Covenant) Act 1995, the Contracts (Rights of Third Parties) Act 1999 and the Agricultural Tenancies Act 1995. In addition the authors have made substantial revisions to existing questions in order to bring them in line with recent case law and statutory provisions, which include the Housing Act 1996 and the Unfair Terms in Consumer Contracts Regulations 1999. The book also contains guidance on examination technique and achieving success in the exam.

Evaluating corporate performance:a critique of economic value added

There has been a revival of interest in economic techniques to measure the value of a firm through the use of economic value added as a technique for measuring such value to shareholders. This technique, based upon the concept of economic value equating to total value, is founded upon the assumptions of classical liberal economic theory. Such techniques have been subject to criticism both from the point of view of the level of adjustment to published accounts needed to make the technique work and from the point of view of the validity of such techniques in actually measuring value in a meaningful context. This paper critiques economic value added techniques as a means of calculating changes in shareholder value, contrasting such techniques with more traditional techniques of measuring value added. It uses the company Severn Trent plc as an actual example in order to evaluate and contrast the techniques in action. The paper demonstrates discrepancies between the calculated results from using economic value added analysis and those reported using conventional accounting measures. It considers the merits of the respective techniques in explaining shareholder and managerial behaviour and the problems with using such techniques in considering the wider stakeholder concept of value. It concludes that this economic value added technique has merits when compared with traditional accounting measures of performance but that it does not provide the universal panacea claimed by its proponents.

Management role in employee participation:a comparative study of multi-national enterprises in India and the U.K.

This research is an Anglo-Indian comparative case study. It studies managerial action in the participation arena of two British multi-nationals i.e. Cadbury Limited and ICI plc. The research was carried out in matched pairs of factories of the above named companies, located in the Midlands of the UK and in Bombay in India. The data for this research was collected through semi-structured interviews with managers and non-management actors, study of company documents and non-participant observation of some participation forums. The research conceptualises the idea of a `participation arena' consisting of the structures, processes, purposes and dynamics of participation. This arena is visualised as broadly reflecting the organisation structure and can be divided into corporate, unit and shopfloor level. Managerial action in this arena is examined in terms of interaction between three sets of factors i.e. company business objectives, strategies and policies; managerial values of power and control; and the responses of unions. Similarities and differences between management action in the home and host plants of the two multi-national companies are also examined. The major findings of the research are as follows. There is significant difference between the participation arena of the parent and the subsidiary company. The latter is marked by absence of higher level participation forums and lack of opportunity for employees to discuss, let alone influence, key decisions. This results from parent company control over key activities of the subsidiary. The similarities in management action in the participation arenas of the two companies in both countries can be attributed to the operation of the three sets of factors mentioned above. Nevertheless, the particular circumstances of each company are a greater influence on managerial action than the national context. Finally, future areas of research in this field are explored.