Systemic autoimmune diseases are characterized by the production of antibodies against a broad range of self-antigens. Recent evidence indicates that the majority of these autoantigens are modified in various ways during cell death. This has led to the hypothesis that the primary immune response in the development of autoimmunity is directed to components of the dying cell. In this article, we summarize data on the modification of autoantigens during cell death and the possible consequences of this for autoimmunity. BioEssays 22:627–636, (...) 2000. © 2000 John Wiley & Sons, Inc. (shrink)

In the Netherlands, the legalization of assisted suicide for persons with a death wish without severe illness, often referred to as persons with “completed life” or “tiredness of life,” is intensel...

Worries about safety of approved drugs have pushed post registration research to become the fastest growing drug research phase. Until recently, phase IV studies were mainly conducted for marketing purposes and run much like a phase III trial—at institutions with experienced investigators and a list of inclusion and exclusion criteria. Innovative phase IV studies involve ordinary physicians in research naïve communities. This brings ethical issues familiar to medical research into clinical practice. As a consequence, individual physicians are challenged to protect (...) scientific integrity and to secure the ethical conduct of research. Several ethical issues need to be addressed in the process of developing a scientifically sound and ethically high principled practice of phase IV research.PHASE IVEssential to phase IV research is the focus on how drugs work in the real world. The research goal may be to explore a specific pharmacological effect, to establish the incidence of adverse reactions, or to determine the effects of long-term administration of a drug. They may also be designed to establish a new clinical indication for a drug.1 Subjects may or may not be randomised, and the studies typically involve large numbers of patient-subjects and physicians.Doubts concerning the scientific rigor and clinical value have put postmarketing research in a poor light. However, high quality phase IV research is badly needed to further pharmaceutical science. First, because it can provide reliable data on the effectiveness, safety and optimal use of a drug in treated populations.2 3 In pre-registration clinical trials , a pharmaceutical product is studied under unrealistic circumstances. Under-representation of women and elderly are common and the concomitant use of medicines is usually extremely restrictive in these trials.4 Second, phase IV can provide much needed data for evidence-based …. (shrink)

The familiar issue of corporate social responsibility takes on a new topic. Added to the list of concerns from affirmative action and environmental integrity is their growing contributions to education. At first glance, the efforts may appear to be ordinary gestures of communal good will in terms of providing computers, sponsoring book covers, and interactive materials provided by Scholastic Magazine. A closer view reveals a targeted market of student life who are vulnerable to commercials placed in these formats. Among the (...) most effective corporate intervention is Channel One News. It offers a newsworthy show but with mandatory commercial viewing. This increasing trend of corporations intervening to assist schools that need more money and/or equipment is disingenuous.In this essay, I present the background of this commercialization of education and demonstrate the violations against student autonomy and integrity. Although there may be utilitarian merits to some interventions, I argue that these infringe upon the moral value of personhood. Advertising in schools in its current practice is immoral on deontological grounds. (shrink)

A recurrent issue in the vast amount of literature on reasoning models in ethics is the role and nature of moral intuitions. In this paper, we start from the view that people who work and live in a certain moral practice usually possess specific moral wisdom. If we manage to incorporate their moral intuitions in ethical reasoning, we can arrive at judgements and (modest) theories that grasp a moral experience that generally cannot be found outside the practice. Reflective equilibrium (RE) (...) provides a framework for balancing moral intuitions, ethical principles and general theories. Nevertheless, persisting problems associated with the use of intuitions need to be addressed. One is the objection that moral intuitions lack the credibility necessary to guide moral reasoning. Ethicists have tried to solve this problem by formulating criteria to separate the “bad” intuitions from the “good” ones at the beginning of the reasoning process. We call this the credible input-justified outcome strategy. An example is the appeal to the common morality by Beauchamp and Childress. We think this approach is unsuccessful. As an alternative, we outline the good reasoning-justified outcome strategy. It connects to a variant of RE in which intuitions from different sources are incorporated. We argue that the elements of RE have different levels of justificatory power at the start of reasoning. In our strategy, each element can gain or lose justificatory power when it is tested in a reasoning process that meets several criteria. (shrink)

A gas in a box is perhaps the most important model system studied in thermodynamics and statistical mechanics. Usually, studies focus on the gas, whereas the box merely serves as an idealized confinement. The present article focuses on the box as the central object and develops a thermodynamic theory by treating the geometric degrees of freedom of the box as the degrees of freedom of a thermodynamic system. Applying standard mathematical methods to the thermody- namics of an empty box allows (...) equations with the same structure as those of cosmology and classical and quantum mechanics to be derived. The simple model system of an empty box is shown to have interesting connections to classical mechanics, special relativity, and quantum field theory. (shrink)

This study investigated the differences between past and future temporal discounting in terms of neural activity in relation to temporal distance. Results show that brain regions are engaged differently in past and future temporal discounting. This is likely because past temporal discounting requires memory reconstruction, whereas future temporal discounting requires the processing of uncertainty about the future. In past temporal discounting, neural activity differed only when preferences were made between rewards received one hour prior and rewards received further in the (...) past. The peak amplitudes of P2 and P3 varied as the temporal distance increased from 2 weeks to 50 years. In future temporal discounting, neural activity differed only when preferences were evaluated between two delayed rewards. The delay conditions and had a significant influence on P2 and N2. Findings indicate the existence of different decision-making systems operating in past and future temporal discounting. (shrink)

Decisions related to animal welfare standards depend on farmer’s multiple goals and values and are constrained by a wide range of external and internal forces. The aim of this paper is twofold, i.e., to develop a theoretical framework for farmers’ AW decisions that incorporates farmers’ goals, use and non-use values and to present an approach to empirically implement the theoretical framework. The farmer as a head of the farm household makes choices regarding production to maximize the utility of the household. (...) The overall utility of the farmer is determined by his multiple objectives. For the analysis of multi-objective problems, the multiple criteria decision - making paradigm provides an appropriate theoretical framework. However, theories from the field of social-psychology are needed to facilitate the identification of all relevant aspects in the decision making. The practical use of the conceptual framework is demonstrated using a simple numerical application of a multi-objective programming model. Two workshops were devoted to examining the scientific consistency and the practical usefulness of the approach. Implementing this approach will increase knowledge of the main factors and barriers that determine farmers’ decisions with regard to AW standards. This knowledge is relevant during the development of new AW concepts that aims to supply products that comply with above-legal AW standards for middle-market segments. (shrink)

Having defined a notion of homology for paired graphs, Métayer ([Ma]) proves a homological correctness criterion for proof nets, and states that for any proof net \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document} $G$\end{document} there exists a Jordan-Hölder decomposition of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document} ${\mathsf H}_0(G)$\end{document}. This decomposition is determined by a certain enumeration of the pairs in \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document} $G$\end{document}. We correct his (...) proof of this fact and show that there exists a 1-1 correspondence between these Jordan-Hölder decompositions of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document} ${\mathsf H}_0(G)$\end{document} and the possible ‘construction-orders’ of the par-net underlying \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document} $G$\end{document}. (shrink)

The expansion of livestock production throughout the world has led to increased demand for high protein animal feed. This expansion has created economic benefits for livestock farmers and other actors in the chain, but also resulted in environmental and social side effects. This study aims to identify a set of sustainability issues that cover the environmental, economic and social dimensions of soymeal and beef production chains. The method applied combines the results of multiple studies, including a literature review and stakeholder (...) surveys. Stakeholder surveys were conducted for three different interest groups and two geographical regions . Our results reveal that the selection of issues in most sustainability assessment studies is a relatively arbitrary decision, while the literature also states that identifying issues is an important step in a sustainability assessment. Defining sustainability issues from a whole chain perspective is important, as issues of sustainability emerge at various stages along the production chain, and are found to vary across stakeholders’ interests. Business stakeholders, for example, perceived economic issues to be more important, whereas the majority of consumer stakeholders and other stakeholders perceived social and environmental issues, respectively, to be more important. Different education levels, knowledge, and living patterns in various geographical regions can affect the stakeholders’ perceptions. The combination of a heterogeneous group of stakeholders and the consideration of multiple chain stages constitutes a useful approach to identify sustainability issues along food chains. (shrink)