Epigenetic and transcriptional variability contribute to the vast diversity of cellular and organismal phenotypes and are key in human health and disease. In this review, we describe different types, sources, and determinants of epigenetic and transcriptional variability, enabling cells and organisms to adapt and evolve to a changing environment. We highlight the latest research and hypotheses on how chromatin structure and the epigenome influence gene expression variability. Further, we provide an overview of challenges in the analysis of biological variability. An (...) improved understanding of the molecular mechanisms underlying epigenetic and transcriptional variability, at both the intra- and inter-individual level, provides great opportunity for disease prevention, better therapeutic approaches, and personalized medicine. Epigenetic and transcriptional variability mediate phenotypic plasticity, enabling adaptation to changing environments. In this review, we describe the sources of inter- and intra-individual variability and discuss epigenetic regulators of gene expression variability, including DNA methylation and chromatin structure. Understanding these molecular mechanisms will improve therapeutic approaches and personalized medicine. (shrink)

Home births continue to constitute only a small percentage of all deliveries in the United States, in part because of concerns about their safety. While the literature is decidedly mixed in regard to the degree of risk, there are several studies that report that home birth may at times entail a small absolute increase in perinatal risks in circumstances that cannot always be anticipated prior to the onset of labor. While the definition of “small” will vary between individuals, and publications (...) vary in the level of risk they ascribe to birth at home, studies with the least methodological flaws and with adequate power often cite an excess death rate in the range of one per thousand.Home birth is, in that regard, but one example of patients’ choices and plans that sometimes carry increased risk or include alternatives that individual physicians feel uncomfortable supporting or recommending. Our intention in this opinion piece is not to advocate for or against home birth. Rather, we recognize that home birth is but one example of a patient choice that might differ from what a provider feels is in a woman’s best interests.In this article we will discuss ethical considerations in such circumstances using home birth as an example. We consider in this article how the ethical principles of respect for autonomy and non-maleficence can be balanced using, among other examples, the choice by some for a home birth. We discuss how absolute rather than relative risk should guide individuals’ evaluation of patient choices. We also consider how in some circumstances, the value and safety added by a physician’s participation may outweigh a potentially small increment in absolute risk that might result from a patient’s decision to deliver at home because of a perceived physician endorsement.We recognize, however, that doctors and midwives participating in choices they have not recommended, or may even believe will lead to or increase risk for adverse outcomes, presents dilemmas and raises important questions. When does respect for patient choice and autonomy become support for poor decision making? When is participation not respectful but enabling? Finally we discuss the role and responsibility of organized medicine in making all births as safe as possible. (shrink)

ABSTRACTPeople often continue to rely on misinformation in their reasoning after they have acknowledged a retraction; this phenomenon is known as the continued-influence effect. Retractions can be particularly ineffective when the retracted misinformation is consistent with a pre-existing worldview. We investigated this effect in the context of depressive rumination. Given the prevalence of depressotypic worldviews in depressive rumination, we hypothesised that depressive rumination may affect the processing of retractions of valenced misinformation; specifically, we predicted that the retraction of negative misinformation (...) might be less effective in depressive ruminators. In two experiments, we found evidence against this hypothesis: in depressive ruminators, retractions of negative misinformation were at least as effective as they were in control participants, and more effective than retractions of positive misinformation. Findings are interpreted in terms of an attentional bias that may enhance the sali... (shrink)

Research on cognitive control has sparked increasing interest in recent years, as it is an important prerequisite for goal oriented human behavior. The paced auditory serial addition task has been used to test and train cognitive control functions. This adaptive, challenging task includes continuous performance feedback. Therefore, additional cognitive control capacities are required to process this information along with the already high task-load. The underlying neural mechanisms, however, are still unclear. To explore the neural signatures of the PASAT and particularly (...) the processing of distractive feedback information, feedback locked event-related potentials were derived from 24 healthy participants during an adaptive 2-back version of the PASAT. Larger neural activation after negative feedback was found for feedback related negativity, P300, and late positive potential. In early stages of feedback processing, a larger difference between positive and negative feedback responses was associated with poorer overall performance. This association was inverted in later stages. Together, our findings indicate stage-dependent associations between neural activation after negative information and cognitive functioning. Conceivably, increased early responses to negative feedback signify distraction, whereas higher activity at later stages reflects cognitive control processes to preserve ongoing performance. (shrink)

To delineate what it means to discover truth, to act in freedom, to be creative, to live authentically, and to aspire to transcend the time and space dimension is the intent of this book. The subject is treated thematically through the analysis of the opposites of materialism and immaterialism, whereas selected traditional and contemporary philosophical themes demonstrate the philosophical mean.

Porté aux nues par les écrivains du XIXè siècle qui voyaient en lui le type même du poète maudit, Byron (1788-1824) a subi au XXè siècle un long purgatoire avant d'être enfin reconnu comme une personnalité littéraire de premier plan. Après les traductions en prose du siècle dernier qui, malgré leur mérite, n'offraient qu'un pâle reflet, on redécouvre aujourd'hui toute la virtuosité d'un poète qui jongle avec les rimes et les rythmes et qui demandait donc à être traduit en vers. (...) Ce choix de poèmes n'a d'autre ambition que de donner une meilleure idée de ses œuvres les plus célèbres. On y retrouva des poèmes de circonstances qui transcendent l'anecdote autobiographique, des morceaux de bravoure qui ont fait la réputation de Childe Harold et de Don Juan, sans oublier cet hymne vibrant à la liberté qu'est le Prisonnier de Chillon et, pour finir, la dernière tirade de Marino Faliero, drame peu connu en France et suprême hommage du poète anglais à la Venise de son imagination. (shrink)

Résumé L’ autrice analyse l’ influence de Richard Wright sur la philosophie féministe de Simone de Beauvoir. Après avoir observé le virage théorique et philosophique que représente Le Deuxième Sexe dans la pensée de Beauvoir, elle en interroge les influences possibles. C’ est chez Richard Wright que l’ autrice trouve les racines de la pensée beauvoirienne de l’ oppression des femmes, de l’ engagement de l’ écrivaine et du féminisme radical selon lequel les femmes doivent se constituer en groupe (...) à part entière pour se libérer. (shrink)

[Peter Simons] Commonsense ontology contains both continuants and occurrents, but are continuants necessary? I argue that they are neither occurrents nor easily replaceable by them. The worst problem for continuants is the question in virtue of what a given continuant exists at a given time. For such truthmakers we must have recourse to occurrents, those vital to the continuant at that time. Continuants are, like abstract objects, invariants under equivalences over occurrents. But they are not abstract, and their being invariants (...) enables us to infer both their lack of temporal parts and that non-invariant predications about them must be relativized to times. \\\ [Joseph Melia] In this paper I try to eliminate occurrents from our ontology. I argue against Simons' position that occurrents are needed to supply truthmakers for existential claims about continuants. Nevertheless, those who would eliminate occurrents still need some account of our willingness to assert sentences that logically entail their existence. Though it turns out to be impossible to paraphrase away our reference to occurrents, I show that the truthmakers for such sentences are facts that involve only continuants. This is enough to allow us to regard our ordinary talk about occurrents as fictional. Finally, I argue that a proper conception of the underlying temporal facts about continuants can both avoid the problematic tensed theory of time and the problem of temporary intrinsics. (shrink)

The exhibition ba [does not equal to] b+a explores the question of how a museum's activities--its mechanisms, modes of operation, and logics--are reflected in the works in its collection. On the occasion of MUSA's tenth anniversary, the museum's program of exhibitions and publications takes a self-reflective turn, shedding light on the specific characteristics of Vienna's municipal art collection, whose origins go back to the 1950s, and raising far-reaching questions concerning the museum as an institution. The assumption underlying the exhibition is (...) that the objects in a museum's collection are crucial to its character. They may seem to be innumerable separate pieces--but the museum is more than their mere juxtaposition. "That which is composed of something in such a way that the whole is a unity," Aristotle writes, "is a unity not as an aggregate is a unity, but as a syllable is. The syllable is not the letters, nor is BA the same as B and A; nor is flesh fire and earth." It is only in the interweaving of the individual components, in their layering and inexhaustible potential constellations, that they engender the necessary density that lets us understand, and interact with, the museum as a living archive. (shrink)

The immediate and guiding aim of this book is to introduce the contemporary reader to the work and thought of Simone Weil.

Simone Weil (1909-1943) was a defining figure of the twentieth century; a philosopher, Christian, resistance fighter, anarchist, feminist, labor activist and teacher. She was described by T. S. Eliot as "a woman of genius, of a kind of genius akin to that of the saints," and by Albert Camus as "the only great spirit of our time." Originally published posthumously in two volumes, these newly reissued notebooks, are among the very few unedited personal writings of Weil's that still survive (...) today. Containing her thoughts on art, love, science, God and the meaning of life, they give context and meaning to Weil's famous works, revealing a unique philosophy in development and offering a rare private glimpse of her singular personality. (shrink)

Contents: "Analysis of Claude Bernard's Introduction to the Study of Experimental Medicine," "Two Unpublished Chapters from She Came to Stay," "Pyrrhus and Cineas," "A Review of The Phenomenology of Perception by Maurice Merleau-Ponty," "Moral Idealism and Political Realism," "Existentialism and Popular Wisdom," "Jean-Paul Sartre," "An Eye for an Eye," "Literature and Metaphysics," "Introduction to an Ethics of Ambiguity," "An Existentialist Looks at Americans," and "What is Existentialism?".

The metaphysics of relations is still in its infancy. We use the idea of truthmaking to gain purchase on this metaphysics. Assuming a modest supervenience conception of truthmaking, where true relational predications require multiply dependent truthmakers, these are indispensable relations. Though some such relations are required, none are needed for internal relatedness, nor for several other kinds of relational predication. Discerning the metaphysically basic kinds of relations is fraught with uncertainties, but must be tackled if progress is to be made.

In these interviews from 1982 and 1985, I ask Beauvoir about her philosophical differences with Jean-Paul Sartre on the issues of voluntarism vs social conditioning and embodiment, individualism vs reciprocity, and ontology vs ethics. We also discuss her influence on Sartre's work, the problems with the current English translation of The Second Sex, her analyses of motherhood and feminist concepts of woman-identity, and her own experience of sexism.

Acquaintance with the Absolute is the first collected volume of essays devoted to the thought of Yves r. Simon, a thinker widely regarded as one of the great teachers and philosophers of our time. Each piece in this collection of essays thoughtfully complements the others to offer a qualifiedly panoramic look at the work and thought of philosopher Yves R. Simon. The six essays presented not only treat some major areas of Simon’s thought, pointing out their lucidity and originality, but (...) also his underpinning metaphysics, so central to his thought. Rather than attempt to present all aspects of this patient, careful, and penetrating thinker, these essays select enough to situate Simon’s philosophical excavations – especially his moral, political and action theory – among contemporary Thomistic philosophy. In defending philosophy as a valid way of knowing, Simon gives us an approach we can use to avoid contemporary dilemmas in the philosophy of science. Simon holds that philosophical truths both justify scientific method as a way of knowing the real and provide a basis for distinguishing what is ontologically significant in a scientific theory from what is not. This view allows us to avoid the apparently irrational conclusions of quantum mechanics without reducing scientific theories to being mere projections of our conceptual systems. Though aspects of some of the essays are suited for students of Simon’s thought, the essays as a whole introduce the less familiar reader to this great thinking and, further, invite him or her to pursue Simon’s own texts. The volume is enhanced by the inclusion of a definitive Yves R. Simon bibliography 1923-1996. The annotated bibliography is cross-reference in detail, revealing the astonishing variety of topics Simon treated. (shrink)

Simone Weil is one of the most profound thinkers of the twentieth century. Her writings encompass an extraordinary breadth of subjects, including philosophy, religion, sociology, and politics. A political activist and resistance fighter, her accomplishments are even more astonishing in light of her death in 1943 at the age of thirty-four. Whilst Weil was concerned with deep philosophical questions - the nature of human thought and human faculties, the limits of language, and thought's contact with reality through mediation, science (...) and beauty - the full significance of her work has frequently been obscured by her categorization as a purely religious writer or Christian mystic. Simone Weil: Basic Writings is an expertly edited anthology of her most important writings, presenting Weil's philosophy as it relates to politics, the nature of work, human nature in its duality, necessity, beauty and goodness. D. K. Levy and Marina Barabas have translated all the extracts anew, including translations of important notes and references missing from existing English language editions of Weil's work. Following an extensive introduction by D. K. Levy which places Weil's life and thought in context, each section opens with a short introduction situating the chosen passages within Weil's oeuvre. Simone Weil: Basic Writings is an outstanding starting point for anyone seeking an introduction to Weil's philosophy, and also essential reading for students and scholars of Weil's thought in related disciplines. (shrink)

In 1971, Ivan Illich wrote that school had become the world religion of a modernized proletariat. Without undoing the power of human interaction undergirding it, understanding how we learn is thus vital to undoing the institutional power of the West – of ‘deschooling’ society. Responding to the conflict between secular and religious schemes of education, the article investigates the ways in which the ‘atheist’ Gilles Deleuze and the ‘mystic’ Simone Weil both employed related stratagems from Stoic philosophy to critique (...) ‘schooling’ construed as the acquisition of, rather than participation in, knowledge. Through a critical reading of the differences between Deleuze's and Weil’s ideas of education, the argument suggests that these differences run aground on the fundamental opposition to a common adversary: that normative pedagogy which trivializes the need to re-school, as well as de-school, society. (shrink)

Background To determine whether fetal care paediatric and maternal–fetal medicine specialists harbour differing attitudes about pregnancy termination for congenital fetal conditions, their perceived responsibilities to pregnant women and fetuses, and the fetus as a patient and whether self-perceived primary responsibilities to fetuses and women and views about the fetus as a patient are associated with attitudes about clinical care.Methods Mail survey of 434 MFM and FCP specialists .Results MFMs were more likely than FCPs to disagree with these statements : ‘the (...) presence of a fetal abnormality is not an appropriate reason for a couple to consider pregnancy termination’ ; ‘the effects that a child born with disabilities might have on marital and family relationships is not an appropriate reason for a couple to consider pregnancy termination’ ; and ‘the cost of healthcare for the future child is not an appropriate reason for a couple to consider pregnancy termination’ . 65% MFMs versus 47% FCPs disagreed that their professional responsibility is to focus primarily on fetal well-being . Specialists did not differ regarding the fetus as a separate patient. Responses about self-perceived responsibility to focus on fetal well-being were associated with clinical practice attitudes.Conclusions Independent of demographic and sociopolitical characteristics, FCPs and MFMs possess divergent ethical sensitivities regarding pregnancy termination, pregnant women and fetuses, which may influence clinical care. (shrink)

Cambridge professor Simon Blackburn is best known to the general public as the author of several books of popular philosophy such as  ink, Being Good andTruth: a Guide for the Perplexed. Academic philosophers also know him as the author of one of the most important books of contemporary moral philosophy, Ruling Passions, and as a former editor of the leading journal Mind.

Since her death in 1986 and the publication of her letters and diaries in 1990, interest in the philosophy of Simone de Beauvoir has never been greater. In this engaging and timely volume, Margaret A. Simons and an international group of philosophers present 16 essays that reveal Beauvoir as one of the century’s most important and influential thinkers. As they set Beauvoir’s work into dialogue with Husserl, Merleau-Ponty, Heidegger, Foucault, Levinas, and others, these essays consider questions such as Beauvoir’s (...) philosophical relationship with Sartre; her ethic of the erotic; her views on marriage, motherhood, and female friendship; and her interpretations of oppression and liberation. This book discusses the full range of Beauvoir’s work, including The Second Sex, her unpublished diaries, autobiographical writings, novels, and philosophical essays, and broadens the scope and interpretive context of her unique philosophy. Contributors are Nancy Bauer, Debra Bergoffen, Suzanne Laba Cataldi, Edward Fullbrook, Eva Gothlin, Sara Heinämaa, Laura Hengehold, Stacy Keltner, Michèle Le Doeuff, Ann Murphy, Shannon M. Mussett, Margaret A. Simons, Ursula Tidd, Andrea Veltman, Karen Vintges, Julie Ward, Gail Weiss. (shrink)

In 1850, Jacob Frerichs produced the first and until now the only edition of Friedrich Schleiermacher’s important lectures on Practical Theology. It is a mix and compilation of students’ transcripts from six different semesters, redundant and at times contradictory, which doesn’t correspond to Schleiermacher’s actual lectures. Most of the transcripts used by Frerichs are still preserved and have now been evaluated for a new edition of Schleiermacher’s Practical Theology. This article disassembles Frerichs’ edition into its components giving evidence for every (...) text passage from which source Frerichs took it. (shrink)

I consider the ‘normative relevance’ argument and the idea of grounding. I diagnose why there appears to be a tension between the conclusion that we are tempted to reach and the intuition that the normative is grounded in or by the non‐normative. Much of what I say turns on the idea of the normative itself. In short, I think that concentrating on this idea can help us see how the tension arises. My aim is to encourage people to reconceptualize the (...) debate so as to begin to offer additional insight. To that end, I spend some time contrasting normativity with evaluation, and then think how the debate may alter if we run it with the latter. I doubt that doing so will solve any problem, and I suspect that what I say will be controversial anyway. But there is some value to changing matters nonetheless. The idea that runs through this paper is that the whole issue is so complex and deep that we should not narrowly construe it with reference only to normativity. (shrink)

Philosophical Investigations, EarlyView.

Precautionary Criminalisation in an Age of Vulnerable Autonomy Content Type Journal Article Category Book Review Pages 1-3 DOI 10.1007/s11572-012-9142-4 Authors Jonathan Simon, Adrian A Kragen Professor of Law, University of California, Berkeley, CA, USA Journal Criminal Law and Philosophy Online ISSN 1871-9805 Print ISSN 1871-9791.

This article treats the political thought of Simón Bolívar, a leading figure in South America's struggle for independence. It describes Bolívar's ideas by reference to both their broadly Atlantic origins and their specifically American concerns, arguing that they comprise a theory of `republican imperialism', paradoxically proposing an essentially imperial project as a means of winning and consolidating independence from European rule. This basic tension is traced through Bolívar's discussions of revolution, constitutions, and territorial unification, and then used to frame a (...) comparison with the founders of the United States. It suggests, in closing, that contextual similarities amongst the American revolutions make them particularly apt subjects for comparative study of the history of political thought. (shrink)

_Gravity and Grace_ shows Weil's religious thoughts and ideas, drawn from many sources - Christian, Jewish, Indian, Greek and Hindu - and focusing on suffering and redemption. It brings the reader face to face with the profoundest levels of existence as Weil explores the relationship of the human condition to the realm of the transcendent.

The pathologies of the democratic public sphere, first articulated by Plato in his attack on rhetoric, have pushed much of deliberative theory out of the mass public and into the study and design of small scale deliberative venues. The move away from the mass public can be seen in a growing split in deliberative theory between theories of democratic deliberation (on the ascendancy) which focus on discrete deliberative initiatives within democracies and theories of deliberative democracy (on the decline) that attempt (...) to tackle the large questions of how the public, or civil society in general, relates to the state. Using rhetoric as the lens through which to view mass democracy, this essay argues that the key to understanding the deliberative potential of the mass public is in the distinction between deliberative and plebiscitary rhetoric. (shrink)