We discuss here a series of testable hypotheses concerning the role of chromosome folding into topologically associating domains (TADs). Several lines of evidence suggest that segmental packaging of chromosomal neighborhoods may underlie features of chromatin that span large domains, such as heterochromatin blocks, association with the nuclear lamina and replication timing. By defining which DNA elements preferentially contact each other, the segmentation of chromosomes into TADs may also underlie many properties of long‐range transcriptional regulation. Several observations suggest that TADs can (...) indeed provide a structural basis to regulatory landscapes, by controlling enhancer sharing and allocation. We also discuss how TADs may shape the evolution of chromosomes, by causing maintenance of synteny over large chromosomal segments. Finally we suggest a series of experiments to challenge these ideas and provide concrete examples illustrating how they could be practically applied. (shrink)

Sentences containing pronouns and indefinite noun phrases can be said toexpress open propositions, propositions which display gaps to be filled.This paper addresses the question what is the linguistic content ofthese expressions, what information they can be said to provide to ahearer, and in what sense the information of a speaker can be said tosupport their utterance. We present and motivate first order notions ofcontent, update and support. The three notions are each defined in acompositional fashion and brought together within a (...) single and coherentframework. (shrink)

For a few decades, patients with Parkinson's disease have been treated with intracerebral transplantations of fetal mesencephalic tissue. The results of open trials have been variable. Double blind, placebo-controlled studies have recently been started in order to further investigate the efficacy of this new medical technique. In this paper we challenge the need for sham surgery in neurotransplantation research on PD patients. Considerations regarding the research subjects' informed consent, therapeutic misconception, the integrity of the human body, and the assessment of (...) risks and benefits argue against sham surgery for patients with PD. Moreover, there is an alternative, less harmful mode of research that can provide the same or comparable scientific evidence. A plea is made for intrapatient research based on quantitative measurements of the patient's pre- and post-operative condition combined with similar research on a reference group of patients who have received the standard treatment. (shrink)

In this article some of the presuppositions that underly the current ideas about decision making capacity, autonomy and independence are critically examined. The focus is on chronic disorders, especially on chronic physical disorders. First, it is argued that the concepts of decision making competence and autonomy, as they are usually applied to the problem of legal (in)competence in the mentally ill, need to be modified and adapted to the situation of the chronically (physically) ill. Second, it is argued that autonomy (...) and dependence must not be considered as two mutually exclusive categories. It is suggested that decision making may take on the form of a more or less conscious decision not to be involved in making all kinds of explicit and deliberate decisions. Elaborating on Agich's distinction between ideal and actual autonomy, the concept of Socratic autonomy is introduced. (shrink)

Medicine does not usually consider the human body from an aesthetic point of view. This article explores the notion of the lived body as aesthetic object in anthropological medicine, concentrating on the views of Buytendijk and Straus on human uprightness and gracefulness. It is argued that their insights constitute a counter-balance to the way the human body is predominantly approached in medicine and medical ethics. In particular, (1) the relationship between anthropological, aesthetic and ethical norms, (2) the possible danger of (...) a naturalistic fallacy, (3) the implications for the care of disabled people and (4) the intrinsic aesthetic quality of the human body are dealt with. (shrink)

Periodic attacks of uncertain origin, where the clinical presentationresembles epilepsy but there is no evidence of a somatic disease, arecalled Pseudo-Epilepsy or Pseudo-Epileptic Attack Disorder (PEAD). PEADmay be called a `non-disease', i.e. a disorder on the fringes ofestablished disease patterns, because it lacks a rationalpathophysiological explanation. The first aim of this article is tocriticize the idea, common in medical science, that diseases are realentities which exist separately from the patient, waiting to bediscovered by the doctor. We argue that doctor and (...) patient construct adisease, and that the construction of the disease PEAD includes manynormative evaluations. The second aim is to provide insight into thesuffering of patients with PEAD. We focus on three aspects of thepatient, identity, autonomy and responsibility. We present somecharacteristic descriptions of (pseudo-)epileptic attacks by FjodorDostoevsky, Gustave Flaubert and Thomas Mann. We argue that diagnosingPEAD reduces a meaningful life event into an insignificant, thoughintriguing, medical phenomenon, and that the patient will not benefitfrom being diagnosed as having PEAD. (shrink)

What is the right thing to do? -- "You have nothing to fear if you've done nothing wrong" -- Between culpable and blameless -- Are all mistakes equal? -- Report, disclose, protect, learn -- A just culture in your organization -- The criminalization of human error -- Is criminalization bad for safety? -- Without prosecutors, there would be no crime -- Three questions for your just culture -- Why do we blame?

During the last decade a “technical” approach has become increasingly influential in health care priority setting. The various country reports illustrate, however, that non-technical considerations cannot be avoided. As they often remain implicit in health care package decisions, this paper aims to make these normative judgements an explicit part of the procedure. More specifically, it aims to integrate different models of distributive justice as well as the principle of solidarity in four different phases of a decision-making procedure, and to identify (...) important moral choices which present themselves. First four important justice models are discussed, then a justification is given for their inclusion in a four-step decision making procedure. This is followed by a discussion of different justice and solidarity problems—with their inherent conceptual difficulties in each of these stages. The paper concludes with a summary of the major moral choices that are to be made in health care package decisions. (shrink)

Among epistemologists, it is not uncommon to relate various forms of epistemic luck to the vexed debate between internalists and externalists. But there are many internalism/externalism debates in epistemology, and it is not always clear how these debates relate to each other. In the present paper I investigate the relation between epistemic luck and prominent internalist and externalist accounts of epistemic justification. I argue that the dichotomy between internalist and externalist concepts of justification can be characterized in terms of epistemic (...) luck. Whereas externalist theories of justification are incompatible with veritic luck but not with reflective luck, the converse is true for internalist theories of justification. These results are found to explain and cohere with some recent findings from elsewhere in epistemology, and support a surprising picture of justification, on which internalism and externalism are complementary rather than contradictory positions. (shrink)

Formal semantics - the scientific study of meaning in natural language - is one of the most fundamental and long-established areas of linguistics. This Handbook offers a comprehensive, yet compact guide to the field, bringing together research from a wide range of world-leading experts. Chapters include coverage of the historical context and foundation of contemporary formal semantics, a survey of the variety of formal/logical approaches to linguistic meaning and an overview of the major areas of research within current semantic theory, (...) broadly conceived. The Handbook also explores the interfaces between semantics and neighbouring disciplines, including research in cognition and computation. This work will be essential reading for students and researchers working in linguistics, philosophy, psychology and computer science. (shrink)

In decisions about inclusion (or exclusion) of health care services in the benefit package, different interpretations of notions like health, health risk, disease, quality of life or necessary care often remain implicit. Yet they can lead to different benefit package decisions. After a brief discussion of these concepts in definitions of the goals of medicine, the various value-judgements implicit in interpretations of key notions in health care are analysed and conclusions are drawn with regard to the composition of decision making (...) bodies at various levels. It is further argued that such a body needs to discuss the various interpretations of key-notions explicitly in the various phases of a priority-setting procedure so that more consistent choices can be made in health care priority setting. (shrink)

The current challenges of implementing responsible innovation can in part be traced back to the assumptions behind the ways of thinking that ground the different pre-existing theories and approaches that are shared under the RI-umbrella. Achieving the ideals of RI, therefore not only requires a shift on an operational and systemic level but also at the paradigm-level. In order to develop a deeper understanding of this paradigm shift, this paper analyses the paradigm-level assumptions that are being brought forward by the (...) different conceptualizations of RI. To this purpose it deploys a pragmatic stance on paradigms that allows discerning ontological and axiological elements shared by the RI community and an accompanying critical hermeneutic research approach that enables the profiling of paradigmatic beliefs and assumptions of accounts of RI. The research surfaces the distance of four salient RI accounts from the currently dominant techno-economic innovation paradigm RI seeks to shift. With this, our contribution helps to raise the self-awareness of the RI community about their presuppositions and the paradigm level barriers and enablers to reaching the RI ideal. This insight is needed for a successful transition to responsible research and innovation practices. (shrink)

This paper presents a case study of the South African operation of a logistics company, operating in a context of short-termism and under-performance. Frustration with managing in this context, and concern that this environment might erode the customer value proposition, prompted an exploration of the question: “How can the business prioritise its investment in intangibles to support sustainable growth in an environment of short-termism and sub-par business performance?” The study followed an inductive grounded theory approach and began with an exploration (...) of the system of short-termism as it was being experienced by the management team. This evolved in an iterative process to include an exploration of the customer value proposition, the organisation’s capabilities and the system of investment in intangibles. Data were collected over a period of 6 months, across a series of four stages as the management team grappled with the short-term financial objectives imposed on them. The data categories were used to develop 214 propositions across all stages. Through the four stages, four artefacts were developed from the propositions a causal loop diagram of the system of short-termism; a documented value proposition; an assessment of the health of the business’ capitals; and a multi-year intangibles investment programme. The findings indicate that a focus on investment in intangible assets can play a vital role in stimulating sustainable value creation in an environment of historically poor returns on investment and pressure for short-term financial results. It is suggested that investment in intangibles can be introduced as a multi-year capabilities investment plan. The study succeeded in getting investment in intangibles approved and the implication is that long-term decision-making can co-exist in an environment of short-termism and low growth. (shrink)

Social health disparities are increasing in most countries around the world. During the past two decades, a large amount of evidence has emerged about the health consequences of social inequalities. Despite such evidence, the concept of medical fairness, as traditionally defined by the World Medical Association, has remained unchallenged and even reinforced by some scholars who emphasize that doctors should remain neutral to the socioeconomic status of their patients when providing clinical care. The inconsistency between public health and clinical care (...) perspectives raises tension between a narrow interpretation of the ethics of justice, which stresses the importance of equality and impartiality, and the ethics of care, which highlights the importance of particularity and individuality in clinical practice. This article analyzes the concept of medical fairness using the emerging evidence that demonstrates the impact of social health disparities on clinical care. It proposes a new approach of medical fairness based on equity rather than on equality and provides a consistent ethical framework based on Paul Ricoeur’s three levels of medical judgments. This integrative framework provides a better balance between public health and clinical care in medical practice. (shrink)

This paper investigates which of the variouslegal notions proposed for human DNA is themost appropriate from an ontological viewpoint – unique legal status, private property, commonproperty, person, or information. The focus is onthe difficulties that private property, commonproperty and person present. By usingHarré''s notion of ``file-self'''' we arguethat, ontologically, the most appropriate legalnotion to be applied is information. This hasconsequences for storage, control and use ofgenetic information as well as identifiablehuman body material.

Digital energy platforms play a central role in the transition toward a more sustainable energy system. This research explores the effect of digital energy platforms on public values. We developed and tested a novel public value framework, combining values already embedded in energy and digitalization regulations and emerging values that have become more relevant in recent debates. We analyzed value changes and potential value tensions. We found that sustainability is prioritized, security is broadened to include cybersecurity, and values relevant for (...) digital technologies, such as control over technology, have also become relevant for the energy system. This has resulted in three value tensions: preserving a well-functioning energy system, self-determination, and ensuring a level playing field and public control. A sustainable energy system requires governments to address these value changes, value tensions, and connected societal and political challenges related to the implementation of digital energy platforms. (shrink)

The Istituto e Museo di Storia della Scienza, Florence, Italy, possesses an astrolabe with five latitude plates that is now attributed to the Duisburg workshop of Gerard Mercator. Although it is known that Mercator made instruments, this is the first surviving example to be identified. Another latitude plate is shown to come from the workshop of the Florentine, Giovan Battista Giusti. A seventh plate, possibly engraved by Rumold Mercator, provides the only known Mercatorian polar stereographic projection. The role of Egnazio (...) Danti, cosmographer to the Grand Duke of Tuscany, in the acquisition of the astrolabe in about 1570 is considered. (shrink)

The 2007 edition of the Amsterdam Colloquium is the Sixteenth in a series which started in 1976. Originally, the Amsterdam Colloquium was an initiative of the Department of Philosophy of the University of Amsterdam. Since 1984 the Colloquium is organized by the Institute for Logic, Language and Computation (ILLC) of the University of Amsterdam.

Formal semantics - the scientific study of meaning in natural language - is one of the most fundamental and long-established areas of linguistics. This Handbook offers a comprehensive, yet compact guide to the field, bringing together research from a wide range of world-leading experts. Chapters include coverage of the historical context and foundation of contemporary formal semantics, a survey of the variety of formal/logical approaches to linguistic meaning and an overview of the major areas of research within current semantic theory, (...) broadly conceived. The Handbook also explores the interfaces between semantics and neighbouring disciplines, including research in cognition and computation. This work will be essential reading for students and researchers working in linguistics, philosophy, psychology and computer science. (shrink)

Pure Type Systems, PTSs, were introduced as a generalization of the type systems of Barendregt's lambda cube and were designed to provide a foundation for actual proof assistants which will verify proofs. Systems of illative combinatory logic or lambda calculus, ICLs, were introduced by Curry and Church as a foundation for logic and mathematics. In an earlier paper we considered two changes to the rules of the PTSs which made these rules more like ICL rules. This led to four kinds (...) of PTSs. Most importantly PTSs are about statements of the form M:A, where M is a term and A a type. In ICLs there are no explicit types and the statements are terms. In this paper we show that for each of the four forms of PTS there is an equivalent form of ICL, sometimes if certain conditions hold. (shrink)

Kozhamthadam Job, b. 1945, the pioneer of science-religion dialogue in India; contributed articles.

Palliative care and euthanasia have become the subject of ethical and political debate in Poland. However, the voice of nurses is rarely heard. The aim of this study is to explore the perception of palliative care and euthanasia among recent university bachelor degree graduates and experienced nurses in Poland. Specific objectives include: self-assessment of the understanding of these terms, recognition of clinical cases, potential acceptability of euthanasia, and an evaluation of attitudes towards palliative care and euthanasia. This is an exploratory (...) study. A convenience sample of 206 recent graduates and 252 experienced nurse practitioners were interviewed. A structured questionnaire was used for collecting and interpreting data. Subjective perception of the terms `palliative care' and `euthanasia' was high and consistent with the recognition of clinical cases. The majority of the nurses excluded euthanasia from palliative care. They recognized personal philosophy of life as the most influential factor affecting attitudes towards euthanasia. The importance of the law was valued more highly by the experienced nurses. (shrink)

In his concept of an anthropological physiology, F.J.J. Buytendijk has tried to lay down the theoretical and scientific foundations for an anthropologically-oriented medicine. The aim of anthropological physiology is to demonstrate, empirically, what being specifically human is in the most elementary physiological functions. This article contains a sketch of Buytendijk''s life and work, an overview of his philosophical-anthropological presuppositions, an outline of his idea of an anthropological physiology and medicine, and a discussion of some episternological and methodological problems. It is (...) demonstrated that Buytendijk''s design of an anthropological physiology is fragmentary and programmatic and that his methodology offers few points of contact for specific anthropological experimental research.Notwithstanding, it is argued that Buytendijk''s description of the subjective, animated body forms a pre-eminent point of reference for all research in physiology and psychology in which the specific human aspect is not ignored beforehand. (shrink)