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?

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)

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)

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)

How do we judge whether an action is morally right or wrong? If an action is wrong, what reason does that give us not to do it? Why should we give such reasons priority over our other concerns and values? In this book, T. M. Scanlon offers new answers to these questions, as they apply to the central part of morality that concerns what we owe to each other. According to his contractualist view, thinking about right and wrong is thinking (...) about what we do in terms that could be justified to others and that they could not reasonably reject. He shows how the special authority of conclusions about right and wrong arises from the value of being related to others in this way, and he shows how familiar moral ideas such as fairness and responsibility can be understood through their role in this process of mutual justification and criticism. Scanlon bases his contractualism on a broader account of reasons, value, and individual well-being that challenges standard views about these crucial notions. He argues that desires do not provide us with reasons, that states of affairs are not the primary bearers of value, and that well-being is not as important for rational decision-making as it is commonly held to be. Scanlon is a pluralist about both moral and non-moral values. He argues that, taking this plurality of values into account, contractualism allows for most of the variability in moral requirements that relativists have claimed, while still accounting for the full force of our judgments of right and wrong. (shrink)

"A beautiful piece of work on the theory of altered states of consciousness ." "Stanislav Grof, M.D. author of Realms of the Human Unconsciousness".

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)

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)

Abstract I argue that the two primary motivations in the literature for positing seemings as sui generis mental states are insufficient to motivate this view. Because of this, epistemological views which attempt to put seemings to work don’t go far enough. It would be better to do the same work by appealing to what makes seeming talk true rather than simply appealing to seeming talk. Content Type Journal Article Pages 1-12 DOI 10.1007/s11406-012-9363-8 Authors T. Ryan Byerly, Department of Philosophy, Baylor (...) University, Waco, TX, USA Journal Philosophia Online ISSN 1574-9274 Print ISSN 0048-3893. (shrink)

Some philosophers have thought that life could only be meaningful if there is no God. For Sartre and Nagel, for example, a God of the traditional classical theistic sort would constrain our powers of self-creative autonomy in ways that would severely detract from the meaning of our lives, possibly even evacuate our lives of all meaning. Some philosophers, by contrast, have thought that life could only be meaningful if there is a God. God and the Meanings of Life is interested (...) in exploring the truth in both these schools of thought, seeking to discover what God could and couldn't do to make life meaningful (as well as what he would and wouldn't do). Mawson espouses a version of the 'amalgam' or 'pluralism' thesis about the issue of life's meaning – in essence, that there are a number of different legitimate meanings of 'meaning' (and indeed 'life') in the question of life's meaning. According to Mawson, God, were he to exist, would help make life meaningful in some of these senses and hinder in some others. He argues that whilst there could be meaning in a Godless universe, there could be other sorts of meaning in a Godly one and that these would be deeper. (shrink)

This is the text of The Lindley Lecture for 1996, given by T.M. Scanlon, an American philosopher.