In order to ensure an adequate and ongoing protection of individuals participating in scientific research, the impacts of new biomedical technologies, such as Next Generation Sequencing , need to be assessed. In this light, a necessary reexamination of the ethical and legal structures framing research could lead to requisite changes in informed consent modalities. This would have implications for Institutional Review Boards , who bear the responsibility of guaranteeing that participants are verifiably informed, and in sufficient detail, to understand the (...) reality of genetic research as it is practiced now. Current literature allowed the identification of key emergent themes related to the consent process when NGS was used in a research setting. (shrink)

The anticipation of ethical issues that may arise with the clinical use of genomic technologies is crucial to envision their future implementation in a manner sensitive to local contexts. Yet, populations in low- and middle-income countries are underrepresented in studies that aim to explore stakeholders’ perspectives on the use of such technologies. Within the framework of a research project entitled “Personalized medicine in the treatment of epilepsy”, we sought to increase inclusiveness by widening the reach of our survey, inviting neurologists (...) from around the world to share their views and practices regarding the use of whole-genome sequencing in clinical neurology and its associated ethics. We discuss herein the compelling scientific and ethical reasons that led us to attempt to recruit neurologists worldwide, despite the lack, in many low- or middle-income countries, of access to genomic technologies. Recruitment procedures and their results are presented and discussed, as well as the barriers we faced. We conclude that inclusive recruitment remains a challenging, albeit necessary and legitimate, endeavour. (shrink)

Background Next Generation Sequencing (NGS) is expected to help find the elusive, causative genetic defects associated with Bipolar Disorder (BD). This article identifies the importance of NGS and further analyses the social and ethical implications of this approach when used in research projects studying BD, as well as other psychiatric ailments, with a view to ensuring the protection of research participants. Methods We performed a systematic review of studies through PubMed, followed by a manual search through the titles and abstracts (...) of original articles, including the reviews, commentaries and letters published in the last five years and dealing with the ethical and social issues raised by NGS technologies and genomics studies of mental disorders, especially BD. A total of 217 studies contributed to identify the themes discussed herein. Results The amount of information generated by NGS renders individuals suffering from BD particularly vulnerable, and increases the need for educational support throughout the consent process, and, subsequently, of genetic counselling, when communicating individual research results and incidental findings to them. Our results highlight the importance and difficulty of respecting participants’ autonomy while avoiding any therapeutic misconception. We also analysed the need for specific regulations on the use and communication of incidental findings, as well as the increasing influence of NGS in health care. Conclusions Shared efforts on the part of researchers and their institutions, Research Ethics Boards as well as participants’ representatives are needed to delineate a tailored consent process so as to better protect research participants. However, health care professionals involved in BD care and treatment need to first determine the scientific validity and clinical utility of NGS-generated findings, and thereafter their prevention and treatment significance. (shrink)

The use of Next Generation Sequencing such as Whole Genome Sequencing is a promising step towards a better understanding and treatment of neurological diseases. WGS can result into unexpected information, and information with uncertain clinical significance. In the context of a Genome Canada project on ‘Personalized Medicine in the Treatment of Epilepsy’, we intended to address these challenges surveying neurologists’ opinions about the type of results that should be returned, and their professional responsibility toward recontacting patients regarding new discovered mutations. (...) Potential participants were contacted through professional organizations or direct invitations. A total of 204 neurologists were recruited. Fifty nine percent indicated that to be conveyed, WGS results should have a demonstrated clinical utility for diagnosis, prognosis or treatment. Yet, 41% deemed appropriate to return results without clinical utility, when they could impact patients’ reproductive decisions, or on patients’ request. Current use of targeted genetic testing and age of patients influenced respondents’ answers. Respondents stated that analysis of genomics data resulting from WGS should be limited to the genes likely to be relevant for the patient’s specific medical condition, so as to limit IFs. Respondents felt responsible to recontact patients and inform them about newly discovered mutations related to the medical condition that triggered the test for as long as they are following up on the patient. Finally, 53.5% of the respondents felt responsible to recontact and inform patients of clinically significant, newly discovered IFs. Our results show the importance of formulating professional guidelines sensitive to the various – and sometimes opposite – viewpoints that may prevail within a same community of practice, as well as flexible so as to be attuned to the characteristics of the neurological conditions that triggered a WGS. (shrink)

Next SectionAn attempt to resolve the controversy regarding the solution of the Sleeping Beauty Problem in the framework of the Many-Worlds Interpretation led to a new controversy regarding the Quantum Sleeping Beauty Problem. We apply the concept of a measure of existence of a world and reach the solution known as ‘thirder’ solution which differs from Peter Lewis’s ‘halfer’ assertion. We argue that this method provides a simple and powerful tool for analysing rational decision theory problems.

The way a rational agent changes her belief in certain propositions/hypotheses in the light of new evidence lies at the heart of Bayesian inference. The basic natural assumption, as summarized in van Fraassen's Reflection Principle, would be that in the absence of new evidence the belief should not change. Yet, there are examples that are claimed to violate this assumption. The apparent paradox presented by such examples, if not settled, would demonstrate the inconsistency and/or incompleteness of the Bayesian approach, and (...) without eliminating this inconsistency, the approach cannot be regarded as scientific. The Sleeping Beauty Problem is just such an example. The existing attempts to solve the problem fall into three categories. The first two share the view that new evidence is absent, but differ about the conclusion of whether Sleeping Beauty should change her belief or not, and why. The third category is characterized by the view that, after all, new evidence is involved. My solution is radically different and does not fall into either of these categories. I deflate the paradox by arguing that the two different degrees of belief presented in the Sleeping Beauty Problem are in fact beliefs in two different propositions, i.e., there is no need to explain the change of belief. The Sleeping Beauty Problem The Problem Deflated 2.1 From contradiction to consistency 2.2 The inanimate version 2.3 Back to SB Summary CiteULike Connotea Del.icio.us What's this? (shrink)

The idea of perfection.--On God and Good.--The sovereignty of good over other concepts.

Iris Murdoch was one of the great philosophers and novelists of the twentieth century and The Sovereignty of Good is her most important and enduring philosophical work. She argues that philosophy has focused, mistakenly, on what it is right to do rather than good to be and that only by restoring the notion of ‘vision’ to moral thinking can this distortion be corrected. This brilliant work shows why Iris Murdoch remains essential reading: a vivid and uncompromising style, a (...) commitment to forceful argument, and a courage to go against the grain. With a foreword by Mary Midgley. (shrink)

There has recently been a good deal of controversy about Landauer's Principle, which is often stated as follows: The erasure of one bit of information in a computational device is necessarily accompanied by a generation of kT ln 2 heat. This is often generalised to the claim that any logically irreversible operation cannot be implemented in a thermodynamically reversible way. John Norton (2005) and Owen Maroney (2005) both argue that Landauer's Principle has not been shown to hold in general, and (...) Maroney offers a method that he claims instantiates the operation reset in a thermodynamically reversible way. In this paper we defend the qualitative form of Landauer's Principle, and clarify its quantitative consequences (assuming the second law of thermodynamics). We analyse in detail what it means for a physical system to implement a logical transformation L, and we make this precise by defining the notion of an L-machine. Then we show that logical irreversibility of L implies thermodynamic irreversibility of every corresponding L-machine. We do this in two ways. First, by assuming the phenomenological validity of the Kelvin statement of the second law, and second, by using information-theoretic reasoning. We illustrate our results with the example of the logical transformation 'reset', and thereby recover the quantitative form of Landauer's Principle. (shrink)

Iris Murdoch once observed: 'philosophy is often a matter of finding occasions on which to say the obvious'. What was obvious to Murdoch, and to all those who read her work, is that Good transcends everything - even God. Throughout her distinguished and prolific writing career, she explored questions of Good and Bad, myth and morality. The framework for Murdoch's questions - and her own conclusions - can be found here.

Iris Murdoch was one of the great philosophers and novelists of the twentieth century and The Sovereignty of Good is her most important and enduring philosophical work. She argues that philosophy has focused, mistakenly, on what it is right to do rather than good to be and that only by restoring the notion of ‘vision’ to moral thinking can this distortion be corrected. This brilliant work shows why Iris Murdoch remains essential reading: a vivid and uncompromising style, a (...) commitment to forceful argument, and a courage to go against the grain. With a foreword by Mary Midgley. (shrink)

Iris Murdoch once observed: 'philosophy is often a matter of finding occasions on which to say the obvious'. What was obvious to Murdoch, and to all those who read her work, is that Good transcends everything - even God. Throughout her distinguished and prolific writing career, she explored questions of Good and Bad, myth and morality. The framework for Murdoch's questions - and her own conclusions - can be found here.

In this classic work of feminist political thought, Iris Marion Young challenges the prevailing reduction of social justice to distributive justice.

Karl Popper famously opposed Marxism in general and its philosophical core – the Marxist dialectic – in particular. As a progressive thinker, Popper saw in dialectic a source of dogmatism damaging to philosophy and political theory. Popper had summarized his views on dialectic in an article that was first delivered in 1937 and subsequently republished as a chapter of his book (2002, pp. 419-451), where he accuses Marxist dialecticians of not tolerating criticism. Ironically, Popper’s view that all Marxist dialecticians dogmatically (...) dismiss any criticism of dialectic by claiming that their opponents do not understand dialectic makes his position no less dogmatic. Indeed, any attempt to criticise Popper’s views on dialectics would be seen only as an additional example of responses by “dogmatic dialecticians”, making his theory essentially immune. This completely prevents dialecticians from being able to criticise Popper’s views. This is exactly the opposite of what the great philosopher wanted. Therefore, for the sake of “anti-dogmatic science” it is desirable and even necessary to defend dialectic. In this work I address several central points about Popper’s criticism of Marxist (materialist) dialectic. In particular, I (a) analyse Popper’s definition of dialectic as the dialectic triad (thesis, anti-thesis, synthesis) and contrast it with a notion of dialectic as a much more complex concept which occurs in dialectical materialism today, where the triad represents only one of the aspects; (b) compare dialectic with the trial and error method; (c) discuss the place of dialectic amongst valid scientific methods: Does dialectic accept logical contradictions; (e) discuss lessons dialecticians should learn from Popper’s criticism. I will test my arguments as to their constructiveness and will demonstrate explicitly the nature of my disagreement with Popper - thereby trying to avoid the “dogmatic dialecticians” response as much as possible. (shrink)

The acclaimed author of The Good Apprentice draws on the entire history of philosophy--and particularly on Plato and Kant--to formulate her own model of morality and demonstrate how thoroughly it is bound up with our daily lives. "An utterly absorbing book".--The Wall Street Journal.

Feedback loops have been identified in a variety of regulatory systems and organisms. While feedback loops of the same type (negative or positive) tend to have properties in common, they can play distinctively diverse roles in different regulatory systems, where they can affect virulence in a pathogenic bacterium, maturation patterns of vertebrate oocytes and transitions through cell cycle phases in eukaryotic cells. This review focuses on the properties and functions of positive feedback in biological systems, including bistability, hysteresis and activation (...) surges. BioEssays 30:542–555, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Horizontal gene transfer advances bacterial evolution. To benefit from horizontally acquired genes, enteric bacteria must overcome silencing caused when the widespread heat‐stable nucleoid structuring (H‐NS) protein binds to AT‐rich horizontally acquired genes. This ability had previously been ascribed to both anti‐silencing proteins outcompeting H‐NS for binding to AT‐rich DNA and RNA polymerase initiating transcription from alternative promoters. However, we now know that pathogenic Salmonella enterica serovar Typhimurium and commensal Escherichia coli break down H‐NS when this silencer is not bound to (...) DNA. Curiously, both species use the same protease – Lon – to destroy H‐NS in distinct environments. Anti‐silencing proteins promote the expression of horizontally acquired genes without binding to them by displacing H‐NS from AT‐rich DNA, thus leaving H‐NS susceptible to proteolysis and decreasing H‐NS amounts overall. Conserved amino acid sequences in the Lon protease and H‐NS cleavage site suggest that diverse bacteria degrade H‐NS to exploit horizontally acquired genes. (shrink)

The facultative intracellular pathogen Salmonella enterica serovar Typhimurium faces multiple environments during infection, including different cell types as well as extracellular fluids. We propose that Salmonella ascertains its cellular location by assessing the Mg2+ concentration of its milieu. A signal transduction system, PhoP/PhoQ, signals Salmonella its presence in a intracellular (low Mg2+) or extracellular (high Mg2+) environment, thereby promoting transcription of genes required for survival within or entry into host cells. The PhoP/PhoQ system is high in a regulatory hierarchy that (...) controls other signal transduction systems that respond to different host cues, enabling the microorganism to determine its precise tissue and cellular location. BioEssays 20:96–101, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

A collection of the author's most influential essays and short works includes her critique of existentialism, her two dialogues on art and religion, key texts on the continuing importance of the sublime, the concept of love, and more.

This latest work from one of the world's leading political philosophers will appeal to audiences from a variety of fields, including philosophy, political science, women's studies, ethnic studies, sociology, and communications studies.

Iris Murdoch's moral philosophy has long influenced contemporary ethics, yet it has not, in general, received the kind of sustained critical attention that it deserves. "Existentialists and Mystics" and "Metaphysics as a Guide to Morals" provide new access to most of Murdoch's philosophical writings and make possible a deeper appreciation of her contribution to current thought. After assessing the recent critical reception of Murdoch's thought, this review places her moral philosophy in the context of contemporary trends in ethics by (...) tracing her influence on the work of Charles Taylor, highlights the distinctive features of her moral philosophy, and suggests future directions for Murdochian ethics. (shrink)

In her long-awaited Responsibility for Justice, Young discusses our responsibilities to address "structural" injustices in which we among many are implicated, often by virtue of participating in a market, such as buying goods produced in sweatshops, or participating in booming housing markets that leave many homeless.

This paper calls attention to a philosophical presupposition, coined here the continuity thesis which underlies and unites the different, often conflicting, hypotheses in the origin of life field. This presupposition, a necessary condition for any scientific investigation of the origin of life problem, has two components. First, it contends that there is no unbridgeable gap between inorganic matter and life. Second, it regards the emergence of life as a highly probable process. Examining several current origin-of-life theories. I indicate the implicit (...) or explicit role played by the continuity thesis in each of them. In addition, I identify the rivals of the thesis within the scientific community — the almost miracle camp. Though adopting the anti-vitalistic aspect of the continuity thesis, this camp regards the emergence of life as involving highly improbable events. Since it seems that the chemistry of the prebiotic stages and of molecular self-organization processes rules out the possibility that life is the result of a happy accident, I claim that the almost miracle view implies in fact, a creationist position. (shrink)

Some philosophical positions maintain that some aspect of reality depends on human practices, cognitive attitudes or sentiments. This paper presents a framework for understanding such positions in a way that renders them immune to a number of natural but allegedly devastating objections.

Many cognitive scientists, having discovered that some computational-level characterization f of a cognitive capacity φ is intractable, invoke heuristics as algorithmic-level explanations of how cognizers compute f. We argue that such explanations are actually dysfunctional, and rebut five possible objections. We then propose computational-level theory revision as a principled and workable alternative.

In this essay I follow one argument strand from Linda Singer's Erotic Welfare. How can we have a forward-looking and affirmative ideal of sexual freedom when the AIDS panic has altered the sexual landscape and instigated new justifications for oppressive sexual disciplines? How can we be sexual subjects when processes of commodification and disciplinary practices have constrained sexual expression while proliferating sexual fetishes? These are some of the questions this book formulates, without answering.

The essay theorizes the responsibilities moral agents may be said to have in relation to global structural social processes that have unjust consequences. How ought moral agents, whether individual or institutional, conceptualize their responsibilities in relation to global injustice? I propose a model of responsibility from social connection as an interpretation of obligations of justice arising from structural social processes. I use the example of justice in transnational processes of production, distribution and marketing of clothing to illustrate operations of structural (...) social processes that extend widely across regions of the world. The social connection model of responsibility says that all agents who contribute by their actions to the structural processes that produce injustice have responsibilities to work to remedy these injustices. I distinguish this model from a more standard model of responsibility, which I call a liability model. I specify five features of the social connection model of responsibility that distinguish it from the liability model: it does not isolate perpetrators; it judges background conditions of action; it is more forward looking than backward looking; its responsibility is essentially shared; and it can be discharged only through collective action. The final section of the essay begins to articulate parameters of reasoning that agents can use for thinking about their own action in relation to structural injustice. a Footnotesa Thanks to David Alexander, Daniel Drezner, David Owen, and Ellen Frankel Paul for comments on an earlier version of this essay. Thanks to David Newstone for research assistance. (shrink)

The essays in this special issue shed new light on the transnational movement and exchange of researchers, data, theories, and scientific objects in the anthropological and genetic study of human populations in the twentieth century. Historians have long stressed how the study of race and human populations in this period served to create a national identity for emerging nation states. More recently, historical narratives of anthropology and human genetics have emphasized the global scale of research networks in these sciences. This (...) issue explores the specific routes, crossings, and interactions between national and international contexts prompted by the study of races and populations. The essays reveal not only how... (shrink)

Feminist social theory and female body experience are the twin themes of Iris Marion Young's twelve outstanding essays written over the past decade and brought together here. Her contributions to social theory raise critical questions about women and citizenship, the relations of capitalism and women's oppression, and the differences between a feminist theory that emphasizes women's difference and one that assumes a gender-neutral humanity. Loosely following a phenomenological method of description, Young's essays on female embodiment discuss female movement, pregnancy, (...) clothing, and the breasted body. In an introduction that situates her work in the context of shifts in feminist theory and politics over the past decade, Young emphasizes the rootedness of her theorizing in a dedicated and seasoned political activism. (shrink)

In this paper, we hypothesize that X chromosome‐associated mechanisms, which affect X‐linked genes and are behind the immunological advantage of females, may also affect X‐linked microRNAs. The human X chromosome contains 10% of all microRNAs detected so far in the human genome. Although the role of most of them has not yet been described, several X chromosome‐located microRNAs have important functions in immunity and cancer. We therefore provide a detailed map of all described microRNAs located on human and mouse X (...) chromosomes, and highlight the ones involved in immune functions and oncogenesis. The unique mode of inheritance of the X chromosome is ultimately the cause of the immune disadvantage of males and the enhanced survival of females following immunological challenges. How these aspects influence X‐linked microRNAs will be a challenge for researchers in the coming years, not only from an evolutionary point of view, but also from the perspective of disease etiology. (shrink)

With regard to organ donation, Germany is an ‘opt-in’ country, which requires explicit consent from donors. The relatives are either asked to decide on behalf of the donors’ preferences, if these are unknown or if the potential donor has explicitly transferred the decision to them. At the core of this policy lies the sociocultural and moral premise of a rational, autonomous individual, whose rights require legal protection in order to guarantee a voluntary decision. In concrete transplantation practices, the family plays (...) an even more important role. Potential donors and their families decide while being embedded in relations, a point which does still not gain full recognition. This particular discrepancy between policy and practice creates conflicts, which remain taboos of academic inquiry and public discourse. Our analysis shows a plurality of the family’s role in the transplantation process, which reveals an inner tension of the organ donation system. This tension provokes epistemic opacity on the one hand and different collective strategies as responses to discursive exclusion on the other. In future deliberations about organ donation, it is important to create spaces for open discussion, but also practices of communicative engagement, which take care of the needs and emotions attached to taboos. (shrink)

This paper defends a conceptualist answer to the question how objects come by their modal properties. It isolates the controversial metaphysical assumptions that are needed to get ontological conceptualism off the ground, outlines the conceptualist answer to the question and shows that conceptualism is not in as bad a shape as some critics have maintained.

Written over a span of more than two decades, the essays by Iris Marion Young collected in this volume describe diverse aspects of women's lived body experience in modern Western societies. Drawing on the ideas of several twentieth century continental philosophers--including Simone de Beauvoir, Martin Heidegger, Luce Irigaray, Julia Kristeva, and Maurice Merleau-Ponty--Young constructs rigorous analytic categories for interpreting embodied subjectivity. The essays combine theoretical description of experience with normative evaluation of the unjust constraints on their freedom and opportunity (...) that continue to burden many women. The lead essay rethinks the purpose of the category of "gender" for feminist theory, after important debates have questioned its usefulness. Other essays include reflection on the meaning of being at home and the need for privacy in old age residences as well as essays that analyze aspects of the experience of women and girls that have received little attention even in feminist theory--such as the sexuality of breasts, or menstruation as punctuation in a woman's life story. Young describes the phenomenology of moving in a pregnant body and the tactile pleasures of clothing. While academically rigorous, the essays are also written with engaging style, incorporating vivid imagery and autobiographical narrative. On Female Body Experience raises issues and takes positions that speak to scholars and students in philosophy, sociology, geography, medicine, nursing, and education. (shrink)

This article presents a weak system of intuitionistic second-order arithmetic, WKV, a subsystem of the one in S.C. Kleene, R.E. Vesley [The Foundations of Intuitionistic Mathematics: Especially in Relation to Recursive Functions, North-Holland Publishing Company, Amsterdam, 1965]. It is then shown that some statements of real analysis, like a version of the Heine–Borel Theorem, and some statements of logic, e.g. compactness of classical proposition calculus, are equivalent to the Fan Theorem in this system.