First-in-human clinical trials represent a critical juncture in the translation of laboratory discoveries. However, because they involve the greatest degree of uncertainty at any point in the drug development process, their initiation is beset by a series of nettlesome ethical questions [1]: has clinical promise been sufficiently demonstrated in animals? Should trial access be restricted to patients with refractory disease? Should trials be viewed as therapeutic? Have researchers adequately minimized risks? The resolution of such ethical questions inevitably turns on claims (...) about future events like harms, therapeutic response, and clinical translation. Recurrent failures in clinical translation, like Eli Lilly's Alzheimer candidate semagacestat, highlight the severe limitations of current methods of prediction. In this case, patients in the active arm of the placebo-controlled trial had earlier onset of dementia and elevated rates of skin cancer [2]. Various authoritative accounts of human research ethics state that decision-making about risk and benefit should be careful, systematic, and non-arbitrary [3]–[5]. Yet, these sources provide little guidance about what kinds of evidence stakeholders should use to ensure their estimates of such events ground responsible ethical decisions. In this article, we suggest that investigators, oversight bodies, and sponsors often base their predictions on a flawed and inappropriately narrow preclinical evidence base. (shrink)

Resumen El presente artículo realiza un análisis de los apoyos otorgados por los cárteles de narcotráfico en México, desde la lectura del aparato crítico de Slavoj Žižek, quien sienta las bases para la interpretación de la ayuda humanitaria como un acto violento. Por lo que, el siguiente texto abarca desde la filosofía Žižekianay el psicoanálisis lacaniano, el fenómeno de la violencia ejercida por la figura del comunista liberal, en un comparativo con el crimen organizado mexicano, intentando desentrañar la estructura básica (...) de la dinámica social que impera en la ayuda humanitaria. Así mismo se define la violencia en general y algunas de sus manifestaciones en la sociedad; estableciendo los elementos esenciales de una ideología, distinguiéndola como una herramienta adecuada para el análisis social, esperado así, resolver cómo se constituye en realidad. Palabras clave: Violencia, sistémica, ayuda humanitaria, goce, realidad.This article presents the analysis of the aid provided by drug trafficking cartels in Mexico. It arises from a critical reading of Slavoj Žižek’s work regarding violence and ideology which lays the foundation for the interpretation of humanitarian aid as a violent act. Hence, the coverage of the article from Žižekian philosophy and Lacanian psychoanalysis, the phenomenon of violence exerted by the figure of the liberal communist, in comparison to Mexican organized crime, trying to unravel the basic structure of social dynamics which prevail in humanitarian aid. Likewise, violence in general and some of its manifestations in society are defined; establishing the essential elements of an ideology, distinguishing it as a suitable tool for social analysis, thus expected, solving how it is actually constituted. Key words: Violence, systemic, humanitarian aid, enjoyment, reality. (shrink)

We propose that social psychological findings on the intuitive bases of moral judgment have broad implications for moral education. The “five foundations theory of intuitive ethics” is applied to explain a longstanding rift in moral education as an ideological disagreement about which moral intuitions should be endorsed and cultivated. The Kohlbergian moral reasoning side has sought to limit the domain of moral education to Harm and Fairness-related moral concerns, whereas character education approaches have tried also to cultivate intuitions concerning the (...) Ingroup, Authority and Purity foundations. Recent attempts to merge the two lines of moral education have not fully addressed this ideological rift, for example by delineating how a single approach could reconcile opposing group- and individual-focused conceptions of moral education. We conclude that psychological research on moral intuition offers a descriptive account of human morality that reveals problems with attempts to create a normative basis for moral education from either side of the ideological divide. (shrink)

The present argument assumes that teaching through modeling attempts to teach the intellectual virtues not primarily as an independent goal of education as, for example, a way to build good character, but for its value to inquiry. I argue that intellectual vices (such as being gullible, dogmatic, pigheaded, or prejudiced)—while harmful to inquiry in certain ways—are essential to its well functioning. Furthermore, to the extent that teaching models critical inquiry, there are educational lessons for which some students ought to take (...) a dogmatic or narrow minded commitment to certain hypotheses or positions; and then, insofar as this modeling works, it will promote these intellectual vices. In Part I of what follows, I develop my argument; in Part II, I respond to the objection that diversity of ideas and attitudes need not—and ought not—call upon the promotion of intellectual vices. (shrink)

O que esta resenha busca é a apresentação e análise do artigo Princess Elisabeth of Bohemia as a Cartesian – publicado como o décimo sétimo capítulo do livro The Oxford Handbook of Descartes and Cartesianism –, da comentadora Lisa Shapiro, também tradutora das correspondências entre Descartes e Elisabeth para a língua inglesa e grande pesquisadora do tema.

Jonathan Dancy works within almost all fields of philosophy but is best known as the leading proponent of moral particularism. Particularism challenges “traditional” moral theories, such as Contractualism, Kantianism and Utilitarianism, in that it denies that moral thought and judgement relies upon, or is made possible by, a set of more or less well-defined, hierarchical principles. During the summer of 2006, the Philosophy Departments of Lund University (Sweden) and the University of Reading (England) began a series of exchanges to (...) take place every other year, alternating between the departments. Andreas Lind and Johan Brännmark arranged to meet Dancy during the first meeting in Lund to talk about questions regarding particularism, moral theory and the shape of the analytical tradition. The major part of the conversation is printed below. (shrink)

Much of the philosophical discussion of explanations has centered around two broad conceptions of what sorts of ‘things’ explanations are – namely, the descriptive and ontic conceptions. Defenders of each argue that scientific psychology has at best little to contribute to the study of explanations. These anti-psychologistic arguments come in two main varieties, the metaphysical and the epistemic. Both varieties trace back to Hempel and recur in the more recent writings of prominent mechanists. The metaphysical arguments attempt to combat psychologism (...) about explanation by doubly dissociating explanations themselves from the commonly associated phenomenology of explanation. The epistemic arguments attempt to combat psychologism by doubly dissociating the good-making features of explanations from the CAPE. I focus on the metaphysical arguments here, for only they directly concern the nature of, as opposed to the evaluation conditions for, explanations. The metaphysical arguments are all shown to equivocate over ‘explanation’, and thus they are no threat to the proposal that sometimes explanations just are psychological events. Such arguments do, nonetheless, gesture towards something important – namely, that the CAPE is neither necessary nor sufficient for explanation in any sense. Similar considerations lead another latter-day mechanist to conclude that no phenomenology of any sort is essential for explanation. What all of these thinkers overlook, however, is that there is another important phenomenological correlate of explanation – namely, finding a happening intelligible or understanding how or why-possibly – and it may well be of the very essence of explanation, at least in the psychological sense. I propose a psychomechanistic theory of intelligibility that accounts for how we can, through finite means, make boundless, endlessly qualified inferences about the implications of our explanations. In closing I note that, although finding a happening intelligible does sometimes engender an unjustified confidence in correctness, we should not overlook how attaining this state does at least put us in a kind of epistemic base camp. I also hint at how intelligibility could turn out to be the ultimate source of the descriptive and ontic conceptions of explanation. (shrink)

The unexpected roles of the microbiota in cancer challenge explanations of carcinogenesis that focus on tumor-intrinsic properties. Most tumors contain bacteria and viruses, and the host’s proximal and distal microbiota influence both cancer incidence and therapeutic responsiveness. Continuing the history of cancer–microbe research, these findings raise a key question: to what extent is the microbiota relevant for clinical oncology? We approach this by critically evaluating three issues: how the microbiota provides a predictive biomarker of cancer growth and therapeutic responsiveness, the (...) microbiota’s causal role(s) in cancer development, and how therapeutic manipulations of the microbiota improve patient outcomes in cancer. Clarifying the conceptual and empirical aspects of the cancer-associated microbiota can orient future research and guide its implementation in clinical oncology. (shrink)

“Responses: A Summing Up” replies to the wide‐ranging contributions to the book. It argues for the complete exclusion of torture from public policy, and defends a broadly consequentialist ethical view of war. It discusses the mutual interplay between society and systems of belief, and urges the relevance of epistemology to dialogue between conflicting ideologies. In discussing an “external moral law,” it expresses doubts about “external reasons.” It discusses the obligation to alleviate poverty, recognizing how hard we find this, and looks (...) for ways of doing better by working with the grain of our psychology. It considers how fantasies about being hard and tough erode the compassion that inhibits atrocities. “Responses: A Summing Up” hopes to express some coherence of outlook toward these very diverse questions. (shrink)

A series of studies investigated the capacity of children between the ages of 7 and 12 to give free and informed consent to participation in psychological research. Children were reasonably accurate in describing the purpose of studies, but many did not understand the possible benefits or especially the possible risks of participating. In several studies children's consent was not affected by the knowledge that their parents had given their permission or by the parents saying that they would not be upset (...) if the children refused. In contrast, other studies found that children were much more likely to stop their participation if the experimenter said explicitly that she would not be upset if they stopped. We suggest that experimenters should pay more attention to describing the possible risks and benefits of participation in research, and that they should also make it clearer to children that they are free to stop once they have begun. (shrink)

Debates in fields studying the biological aspects of aging and longevity, such as biogerontology, are often split between ‘anti-aging’ approaches aimed largely at treating diseases and those focusing more on maintaining, promoting, and even enhancing health. However, it is far from clear what this ‘health’ is that would be maintained, promoted, or enhanced. Interestingly, what few have yet to fully reflect on is that there is still no theory of health within the health or aging sciences that would provide an (...) integrative explanatory framework akin to other scientific theories. After clarifying why such a theory could be useful, I discuss five general features of medical theories that could be used to evaluate the utility of a given proposal. With these features in hand, I suggest that philosophers and scientists work together on analyzing actual medical research (experimental analysis), and the ways in which a theoretical construct of ‘health’ is being progressively identified and measured therein. I conclude by suggesting that research fields studying stress and aging might be particularly helpful in developing candidates for theory construction due to their broad scope, increasing specificity, and potential for providing integrative explanations. (shrink)

The first phase of Sartre’s philosophical publications is marked by an apparent ambivalence towards Husserl’s transcendental turn. Sartre accepts both major aspects of that turn, the phenomenological reduction and the use of transcendental argumentation. Yet his rejection of the transcendental ego that Husserl derives from this transcendental turn overlooks an obvious transcendental argument in favour of it. His books on emotion and imagination, moreover, make only very brief comments about the transcendental constitution of the world of experience. In each case, (...) these appear at the end of the book and can seem to contradict the book’s central analysis. The problem underlying these features of his works of phenomenological psychology is clarified and resolved, however, when Sartre articulates his own transcendental phenomenology and ontology in Being and Nothingness a decade after he first encountered the work of Husserl. This resolution raises a new problem that animates the next phase of his philosophy. (shrink)

One important argument for the free market is that of the ‘invisible hand’ or ‘private vices, public virtues’. That is, individual profit-seeking behaviour by suppliers will lead to better quality, lower priced goods for consumers than could be achieved by other means. Where this is so the market may be to the benefit of all, including the worst off. However, reflection on a range of cases – including what is here called the Titanic Puzzle, introduced by Thomas Schelling - shows (...) that this is not always so. Where there are important market failures which may not be correctable within the market, the goal of helping the worst off and vulnerable can sometimes be best served by setting up structures which generate common interests between supplier and consumer. The goods considered here are termed ‘high-fidelity slow-release’ goods. They are those where consumption of the good is a lengthy or deferred process, ‘escape costs’ are high, and the quality of the good may vary over the life of the exchange, subject to the influence of the supplier even after purchase. Many long term financial products, and other goods such as education, plausibly have such character. An unregulated market for such goods is highly problematic. (shrink)

The decision to initiate invasive, first-in-human trials involving Parkinson’s disease presents a vexing ethical challenge. Such studies present significant surgical risks, and high degrees of uncertainty about intervention risks and biological effects. We argue that maintaining a favorable riskbenefit balance in such circumstances requires a higher than usual degree of confidence that protocols will lead to significant direct and/or social benefits. One critical way of promoting such confidence is through the application of stringent evidentiary standards for preclinical studies. We close (...) with a series of recommendations for strengthening the internal and external validity of preclinical studies, reducing their tendency toward optimism and publication biases, and improving the knowledge base used to design and evaluate preclinical studies. (shrink)

An introduction to the motivations and mechanics of upper and lower probabilities, from a lecture given at the Northern Institute of Philosophy in 2010.

Oxford Studies in Philosophy of Religion is an annual volume offering a regular snapshot of state-of-the-art work in this longstanding area of philosophy that has seen an explosive growth of interest over the past half century. Under the guidance of a distinguished editorial board, it publishes exemplary papers in any area of philosophy of religion.