A large body of evidence on the activity of regulatory T (Treg) cells was gathered during the last decade, and a similar number of reviews and opinion papers attempted to integrate the experimental findings. The abundant literature clearly delineates an exciting area of research but also underlines some major controversies. A linear cause–result interpretation of experimental maneuvers often ignores the fact that the activity of Treg cells is orchestrated with the effector T (Teff) cells within an intricate network of physiological (...) immune homeostasis. Every modulation of the activity of the effector (cytotoxic) immune system revolves to affect the activity of regulatory (suppressive) cells through elaborate feedback loops of negative and positive regulation. The lack of IL‐2 production by innate Treg cells makes this cytokine a prime coupler of the effector and suppressive mechanisms. Here we attempt to integrate evidence that delineates the involvement of IL‐2 in primary and secondary feedback loops that regulate the activity of suppressive cells within the elaborate network of physiological immune homeostasis.©2007 Wiley Periodicals, Inc BioEssays 30:875–888, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Most theories and hypotheses in psychology are verbal in nature, yet their evaluation overwhelmingly relies on inferential statistical procedures. The validity of the move from qualitative to quantitative analysis depends on the verbal and statistical expressions of a hypothesis being closely aligned – that is, that the two must refer to roughly the same set of hypothetical observations. Here, I argue that many applications of statistical inference in psychology fail to meet this basic condition. Focusing on the most widely used (...) class of model in psychology – the linear mixed model – I explore the consequences of failing to statistically operationalize verbal hypotheses in a way that respects researchers' actual generalization intentions. I demonstrate that although the “random effect” formalism is used pervasively in psychology to model intersubject variability, few researchers accord the same treatment to other variables they clearly intend to generalize over. The under-specification of random effects imposes far stronger constraints on the generalizability of results than most researchers appreciate. Ignoring these constraints can dramatically inflate false-positive rates, and often leads researchers to draw sweeping verbal generalizations that lack a meaningful connection to the statistical quantities they are putatively based on. I argue that failure to take the alignment between verbal and statistical expressions seriously lies at the heart of many of psychology's ongoing problems, and conclude with a discussion of several potential avenues for improvement. (shrink)

The 38 commentaries on the target article span a broad range of disciplines and perspectives. I have organized my response to the commentaries around three broad questions: First, how serious are the problems discussed in the target article? Second, are there are other, potentially more productive, ways to think about the issues that the target article framed in terms of generalizability? And third, what, if anything, should we collectively do about these problems?

At the very beginning of L’Homme-Machine, La Mettrie claims that Leibnizians with their monads have “rather spiritualized matter than materialized the soul”; a few years later Pierre-Louis Moreau de Maupertuis, President of the Berlin Academy of Sciences and natural philosopher with a strong interest in the modes of transmission of ‘genetic’ information, conceived of living minima which he termed molecules, “endowed with desire, memory and intelligence,” in his Système de la nature ou Essai sur les corps organisés. This text first (...) appeared in Latin in 1751 under the title Dissertatio inauguralis metaphysica de universali naturae systemate, with the pseudonym Dr Baumann; it was translated by Maupertuis in 1754 as Essai sur la formation des corps organisés and was later included in his 1756 Œuvres under the title Système de la nature. Now, it is clear that Maupertuis was a kind of Leibnizian; and that his molecule possessed higher-level, ‘mental’ properties. In that sense he falls under the first category described by La Mettrie. But he was also involved in a debate on this issue with Diderot, who put forth a sustained critique of Maupertuis’ theory of the molecule in the additions to his 1753 Pensées sur l’interprétation de la nature. Where Maupertuis attributes higher-level properties to his living minima, Diderot argues that these properties are ‘organizational’, i.e., they can only be properties of the whole. At issue here is the degree of commitment to a form of materialism. (shrink)

"This is an excellent textbook on Neoplatonism which gives the reader a very concise and lucid overview of the basic doctrines and leading thinkers of the last great philosophy to emerge before the Christianization of the Roman Empire. I’ve no doubt that my students next semester will benefit from the analyses contained in the book. The contents of the chapters are very informative and adequately place developments in their socio-cultural context." --Michael B. Simmons, Auburn University at Montgomery.

Yarkoni argues that researchers making broad inferences often use impoverished statistical models that fail to include important sources of variation as random effects. We argue, however, that for many common study designs, random effects are inappropriate and insufficient to draw general inferences, as the source of variation is not random, but systematic.

In his Philosophical Inquiry concerning Human Liberty (1717), the English deist Anthony Collins proposed a complete determinist account of the human mind and action, partly inspired by his mentor Locke, but also by elements from Bayle, Leibniz and other Continental sources. It is a determinism which does not neglect the question of the specific status of the mind but rather seeks to provide a causal account of mental activity and volition in particular; it is a ‘volitional determinism’. Some decades later, (...) Diderot articulates a very similar determinism, which seeks to recognize the existence of “causes proper to man” (as he says in the Réfutation d’Helvétius). The difference with Collins is that now biological factors are being taken into account. Obviously both the ‘volitional’ and the ‘biological’ forms of determinism are noteworthy inasmuch as they change our picture of the nature of determinism itself, but my interest here is to compare these two determinist arguments, both of which are broadly Spinozist in nature – and as such belong to what Jonathan Israel called in his recent book “the radical Enlightenment,” i.e. a kind of underground Enlightenment constituted by Spinozism – and to see how Collins’ specifically psychological vision and Diderot’s specifically biological vision correspond to their two separate national contexts: determinism in France in the mid-1750s was a much more medico-biological affair than English determinism, which appears to be on a ‘path’ leading to Mill and associationist psychology. (shrink)

This volume emphasizes the diversity and fruitfulness of early modern mechanism as a program, as a concept, as a model. Mechanistic study of the living body but also of the mind and mental processes are examined in careful historical focus, dealing with figures ranging from the first-rank (Bacon, Descartes, Spinoza, Cudworth, Gassendi, Locke, Leibniz, Kant) to less well-known individuals (Scaliger, Martini) or prominent natural philosophers who have been neglected in recent years (Willis, Steno, etc.). The volume moves from early modern (...) medicine and physiology to late Enlightenment and even early 19th-century psychology, always maintaining a conceptual focus. It is a contribution to a newly active field in the history and philosophy of early modern life science. It is of interest to scholars studying the history of medicine and the development of mechanistic theories. (shrink)

The living body appears like an endlessly renewable reservoir of authenticity, hope, and taboo. But, for the sake of conceptual clarity, we are often been told that the (mere) body should be distinguished from the flesh. That is, it’s undeniable that I have a body; that I notice yours; that we worry about their birth and death and upkeep. But the flesh is a more transcendentalized, loaded concept – not least given its frequently religious background (incarnation: the Word made Flesh). (...) It is the body ‘kicked upstairs’, ‘bumped up’ one ontological level. Flesh is like a mantra, an obsessive leitmotif. Is the difference just one of abstraction? Indeed, crucial to the narrative of phenomenology (most obviously in Merleau-Ponty but really, throughout, including in enactivism), to the story of ancestor worship and identity it tells itself and its acolytes around the campfire, is a basic distinction between the merely physical body and the flesh as something requiring ‘mineness’, namely, an understanding of it as uniquely ‘my own’, a feeling of ‘what it is like to be embodied’. This goes back to the Husserlian distinction between Körper, ‘body’ in the sense of one body among others in a vast mechanistic universe of bodies, and Leib, ‘flesh’ in the sense of a subjectivity which is the locus of experience. In this essay I reflect on this vision of the body’s authenticity and its costs, and contrast it with insights derived from Georges Canguilhem, whose critique of mechanism/mechanicism is not done in the name of a wholescale organicism and/or an unproblematized éloge of embodiment and privacy. (shrink)

Ce livre étudie, à travers une série d'épisodes allant de la philosophie des Lumières à notre époque, le problème du matérialisme dans l'histoire de la philosophie et l’histoire des sciences. Comment comprendre les spécificités de l’histoire du matérialisme, des Lumières à nos jours, au sein de la grande histoire de la philosophie et de l’histoire des sciences ? Quelle est l’actualité de l’opposition classique entre le corps et l’esprit ? Qu’est-ce que le rire ou le rêve peuvent nous apprendre du (...) matérialisme ? En traversant l’histoire de ce concept jusqu’à l’émergence d’un « nouveau matérialisme » contemporain, l’ouvrage vise à revitaliser le matérialisme et sa lecture. -/- . (shrink)

Principlism aims to provide a framework to help those working in medicine both to identify moral problems and to make decisions about what to do. For it to meet this aim, the principles included within it must express values that all morally serious people share (or ought to share), and there must be no other values that all morally serious people share (or ought to share). This paper challenges the latter of these claims. I will argue that as a descriptive (...) claim about what values morally serious people do in fact share, principlism is inadequate; more principles would be needed to make this claim true. Furthermore, I will argue that while, taken as a claim about what principles we ought to share, principlism could turn out to be correct, it is either unsupported or unable to meet its aims. The only way in which principlists can avoid these problems is to add to the current four principles. (shrink)

Originally published in 1955. The Madhyamika philosophy is, in the author's view, the philosophy which created a revolution in Buddhism and through that in the whole range of Indian philosophy. This volume is a study of the Madhyamika philosophy in all its important aspects and is divided into three parts: Historical: this traces the origin and development of the Madhyamika philosophy. The second part concentrates on a full and critical exposition of the Madhyamika philosophy, the structure of its dialectic, its (...) conception of the Absolute and its ethics and religion. The last part of the book compares the Madhyamika with some of the well-known dialectical systems of the West (Kant, Hegel and Bradley) and undertakes a short study of the different absolutisms (Madhyamika, Vijnanavada and the Vedanta). (shrink)

In some places consumption of alcohol raises serious public health issues. One recent proposal for addressing these issues has been to set a minimum price at which a unit of alcohol can be sold. In this paper I argue that such a policy, while it may have substantial health benefits, is ethically problematic. This is primarily because it unfairly places considerable burdens on those already most disadvantaged in society. In addition, such policies are poorly targeted if our concern is with (...) preventing the harms drinkers pose to other people. (shrink)

The integration of normative analysis with empirical data often remains unclear despite the availability of many empirical bioethics methodologies. This paper sought bioethics scholars’ experiences and reflections of doing empirical bioethics research to feed these practical insights into the debate on methods. We interviewed twenty-six participants who revealed their process of integrating the normative and the empirical. From the analysis of the data, we first used the themes to identify the methodological content. That is, we show participants’ use of familiar (...) methods explained as “back-and-forth” methods (reflective equilibrium), followed by dialogical methods where collaboration was seen as a better way of doing integration. Thereafter, we highlight methods that were deemed as inherent integration approaches, where the normative and the empirical were intertwined from the start of the research project. Second, we used the themes to express not only how we interpreted what was said but also how things were said. In this, we describe an air of uncertainty and overall vagueness that surrounded the above methods. We conclude that the indeterminacy of integration methods is a double-edged sword. It allows for flexibility but also risks obscuring a lack of understanding of the theoretical-methodological underpinnings of empirical bioethics research methods. (shrink)

Synthetic biologists aim to generate biological organisms according to rational design principles. Their work may have many beneficial applications, but it also raises potentially serious ethical concerns. In this article, we consider what attention the discipline demands from bioethicists. We argue that the most important issue for ethicists to examine is the risk that knowledge from synthetic biology will be misused, for example, in biological terrorism or warfare. To adequately address this concern, bioethics will need to broaden its scope, contemplating (...) not just the means by which scientific knowledge is produced, but also what kinds of knowledge should be sought and disseminated. (shrink)

On the surface, it seems plausible that the goodness or badness of an agent’s actions should be completely irrelevant to the question of whether she performed them intentionally, but there is growing evidence that ascriptions of intentional actions are affected by moral considerations. Joshua Knobe, for instance, has recently published a series of groundbreaking papers (2003a, 2003b, 2004) in which he suggests that people’s judgments concerning the intentionality of an action may sometimes depend on what they think about the action (...) – morally speaking. One of the more interesting results of Knobe’s psychological experiments is the discovery that people may have a lower threshold for judging that lucky (or unskilled) actions are intentional when these actions are praiseworthy or blameworthy than they do for judging that equally lucky (or unskilled) morally neutral actions are intentional. In this paper I show that this discovery – when supplemented with some additional empirical data – gives us a way of shedding new light on a controversy that was sparked by Ronald Butler in 1977 when he posed the following problem to the readers of Analysis. (shrink)