Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR and SPINK1 variants were associated with pancreatitis risk. We now report two associations at genome-wide significance identified and replicated at PRSS1-PRSS2 and X-linked CLDN2 through a two-stage genome-wide study. The PRSS1 variant likely affects disease susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is (...) associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men. © 2012 Nature America, Inc. All rights reserved. (shrink)

This chapter contains sections titled: Introduction: Rational Decisions as an Ideal Rational Decision Making? Assumptions and Difficulties: Preferences, Outcome Spaces, and Probabilities in the World Reasons without Decisions What Kinds of Reasons? The Failure of RCT as a Unifying Principle The Failures of RCT and Rethinking Rationality.

The dissertation explores the way that large-scale research projects in human genetics influence and are influenced by various social and political issues in contemporary U.S. society. In short, the dissertation argues that the same cultural assumptions which make research projects like the Human Genome Project and human behavioral genetics research seem like promising and worthwhile endeavors simultaneously lead to the results of these projects getting used to define the terms that various social issues are discussed in. In cases where the (...) issues involve conflicting agendas, those cultural assumptions that drive the research projects often point towards a specific form of resolution, a form that is often implicitly or explicitly supported by the results of the research projects themselves. ;There is, in other words, a complex relationship of mutual support between certain kinds of research projects in human genetics, the legal and social decisions made in various areas in political life, and the kinds of discourse that can exist around those same areas. This relationship is pernicious insofar as those assumptions that encourage the research and influence the way the research is used are assumptions that many people would question the wisdom of uncritically accepting. And indeed, they are assumptions that, I argue, have strong racist and sexist overtones, assumptions born out of a radically anti-egalitarian framework. Political decisions and social discourse that might otherwise seem radically racist, sexist, or classist can, once they are being made in the shadow of research undertaken under these same kinds of assumptions, be made to seem somehow natural, inevitable, or at the very least, scientifically well-motivated. (shrink)

It is illegitimate to read any ontology about "race" off of biological theory or data. Indeed, the technical meaning of "genetic variation" is fluid, and there is no single theoretical agreed-upon criterion for defining and distinguishing populations (or groups or clusters) given a particular set of genetic variation data. Thus, by analyzing three formal senses of "genetic variation"—diversity, differentiation, and heterozygosity—we argue that the use of biological theory for making epistemic claims about "race" can only seem plausible when it relies (...) on the user’s own assumptions about race; the move from biological measures to claims about “race” inevitably amounts to a pernicious reification. We also excavate assumptions in the history of the technical discourse over the concept of "race" (e.g., Livingstone's and Dobzhansky's 1962 exchange, Edwards' 2003 response to Lewontin 1972, as well as contemporary discussions of cladistic "race", and "races" as clusters). We show that claims about the existence (or non-existence) of "race" are underdetermined by biological facts, methods, and theories. Biological theory does not force the concept of "race" upon us; our social discourse, social ontology, and social expectations do. We become prisoners of our abstractions at our own hands, and at our own expense. (shrink)

This paper distinguishes three concepts of "race": bio-genomic cluster/race, biological race, and social race. We map out realism, antirealism, and conventionalism about each of these, in three important historical episodes: Frank Livingstone and Theodosius Dobzhansky in 1962, A.W.F. Edwards' 2003 response to Lewontin (1972), and contemporary discourse. Semantics is especially crucial to the first episode, while normativity is central to the second. Upon inspection, each episode also reveals a variety of commitments to the metaphysics of race. We conclude by interrogating (...) the relevance of these scientific discussions for political positions and a post-racial future. (shrink)

Madole & Harden argue that just as the results of randomized controlled trials (RCTs) represent gains in causal knowledge and are useful, despite their limitations, so too are the findings of human behavior genetics. We argue that this analogy is misleading. Unlike RCTs, the results of human behavior genetics research cannot suggest efficacious interventions, nor point toward future research.

We attempt to improve the understanding of the notion of agene being `for a phenotypic trait or traits. Considering theimplicit functional ascription of one thing being `for another,we submit a more restrictive version of `gene for talk.Accordingly, genes are only to be thought of as being forphenotypic traits when good evidence is available that thepresence or prevalence of the gene in a population is the resultof natural selection on that particular trait, and that theassociation between that trait and the gene (...) in question isdemonstrably causal. It is therefore necessary to gatherstatistical, biochemical, historical, as well as ecologicalinformation before properly claiming that a gene is for aphenotypic trait. Instead of hampering practical use of the `genefor talk, our approach aims at stimulating much needed researchinto the functional ecology and comparative evolutionary biologyof gene action. (shrink)

Some authors defending the “hereditarian” hypothesis with respect to differences in average IQ scores between populations have argued that the sorts of environmental variation hypothesized by some researchers rejecting the hereditarian position should leave discoverable statistical traces, namely changes in the overall variance of scores or in variance–covariance matrices relating scores to other variables. In this paper, I argue that the claims regarding the discoverability of such statistical signals are broadly mistaken—there is no good reason to suspect that the hypothesized (...) environmental causes would leave detectable traces of the sorts suggested. As there remains no way to gather evidence that would permit the direct refutation of the environmental hypotheses, and no direct evidence for the hereditarian position, it remains the case, I argue, that the hereditarian position is unsupported by current evidence. (shrink)

This article is an introduction to the Synthese Special Issue, Philosophy of Epidemiology. The overall goals of the issue are to revisit the state of philosophy of epidemiology and to provide a forum for new voices, approaches, and perspectives in the philosophy of epidemiology literature. The introduction begins by drawing on Geoffrey Rose’s work on how to conceptualize and design interventions for populations, rather than individuals. It then goes on to highlight some themes that emerged in the articles that make (...) up the issue: philosophy of epidemiology and epidemiological theory—what they are and what they ought to be, pluralism in measurement and causal attribution, epistemic and non-epistemic values in disputes epidemiological practices, decentering philosophy of epidemiology’s Eurocentrism, letting pragmatism guide uses of big data in epidemiology, and revisiting the lessons of classic texts in epidemiological causal inference. The introduction concludes with comments on a philosophy of epidemiology debate we see on, regarding the politics of philosophy of epidemiology. (shrink)

Matthen (Philos Sci 76(4):464–487, 2009) argues that explanations of evolutionary change that appeal to natural selection are statistically abstractive explanations, explanations that ignore some possible explanatory partitions that in fact impact the outcome. This recognition highlights a difficulty with making selective analyses fully rigorous. Natural selection is not about the details of what happens to any particular organism, nor, by extension, to the details of what happens in any particular population. Since selective accounts focus on tendencies, those factors that impact (...) the actual outcomes but do not impact the tendencies must be excluded. So, in order to properly exclude the factors irrelevant to selection, the relevant factors must be identified, and physical processes, environments, and populations individuated on the basis of being relevantly similar for the purposes of selective accounts. Natural selection, on this view, becomes in part a measure of the robustness of particular kinds of outcomes given variations over some kinds of inputs. (shrink)

This book initiates the discussion between psychoanalysis and recent humanist and social scientific interest in a fundamental contemporary topic – the nonhuman. The authors question where we situate the subject in current critical investigations of a nonanthropoentric universe. In doing so they unravel a less-than-human theory of the subject; explore implications of Lacanian teachings in relation to the environment, freedom, and biopolitics; and investigate the subjective enjoyments of and anxieties over nonhumans in literature, film, and digital media. This innovative volume (...) fills a valuable gap in the literature, extending investigations into an important and topical strand of the social sciences for both analytic and pedagogical purposes. (shrink)

Recently, Estes and Arnold claimed to have “solved” the paradox of evolutionary stasis; they claim that stabilizing selection, and only stabilizing selection, can explain the patterns of evolutionary divergence observed over “all timescales.” While Estes and Arnold clearly think that they have identified the processes that produce evolutionary stasis, they have not. Instead, Estes and Arnold identify a particular evolutionary pattern but not the processes that produce that pattern. This mistake is important; the slippage between pattern and process is common (...) in population and quantitative genetics and contributes to a persistent misunderstanding of the nature of explanations in evolutionary biology. †To contact the author, please write to: Philosophy Department, 208 Hovland Hall, Oregon State University, Corvallis, OR 97331‐3902; e‐mail: [email protected]. (shrink)

We argue that heritability estimates cannot be used to make informed judgments about the populations from which they are drawn. Furthermore, predicting changes in heritability from population changes is likely impossible, and of limited value. We add that the attempt to separate human environments into cultural and non-cultural components does not advance our understanding of the environmental multiplier effect.

“What does it mean to say that we live in a secular age?” This apparently simple question opens into the massive, provocative, and complex A Secular Age, where Charles Taylor positions secularism as a defining feature of the modern world, not the mere absence of religion, and casts light on the experience of transcendence that scientistic explanations of the world tend to neglect. -/- In Varieties of Secularism in a Secular Age, a prominent and varied group of scholars chart the (...) conversations in which A Secular Age intervenes and address wider questions of secularism and secularity. The distinguished contributors include Robert Bellah, José Casanova, Nilüfer Göle, William E. Connolly, Wendy Brown, Simon During, Colin Jager, Jon Butler, Jonathan Sheehan, Akeel Bilgrami, John Milbank, and Saba Mahmood. -/- Varieties of Secularism in a Secular Age is edited by Michael Warner, Jonathan VanAntwerpen, and Craig Calhoun. (shrink)

This paper responds to the commentaries from Stacy Carter and Alan Cribb. We pick up on two main themes in our response. First, we reflect on how the process of setting standards for empirical bioethics research entails drawing boundaries around what research counts as empirical bioethics research, and we discuss whether the standards agreed in the consensus process draw these boundaries correctly. Second, we expand on the discussion in the original paper of the role and significance of the concept of (...) ‘integrating’ empirical methods and ethical argument as a standard for research practice within empirical bioethics. (shrink)

Hart commences his essays by stating what he thinks is the search and its concomitant questions. The search he asserts is for principles to justify punishment. Unfortunately, no attempt is made to describe criteria of justification, let alone what is meant by principles. The questions that arise are in terms of giving a general justification for punishing individuals and for determining the severity of that punishment; and of establishing the appropriate method for selection of objects of punishment. No reference is (...) made to a general societal system, nor to the nature of a whole criminal process functioning from statutes through police, to courts and judges. He then describes a "General Justifying Aim" and a system of distribution of punishment. (shrink)

The knowability paradox threatens metaphysical or semantical antirealism, the view that truth is epistemic, by revealing an awful consequence of the claim [i] that all truths are knowable. Various attempts have been made to find a way out of the paradox.

People attribute purposes in both mundane and profound ways—such as when thinking about the purpose of a knife and the purpose of a life. In three studies (total N = 13,720 observations from N = 3,430 participants), we tested whether these seemingly very different forms of purpose attributions might actually involve the same cognitive processes. We examined the impacts of four factors on purpose attributions in six domains (artifacts, social institutions, animals, body parts, sacred objects, and human lives). Study 1 (...) manipulated what items in each domain were originally created for (original design) and how people currently use them (present practice). Study 2 manipulated whether items are good at achieving a goal (effectiveness) and whether the goal itself is good (morality). We found effects of each factor in every domain. However, whereas morality and effectiveness had remarkably similar effects across domains, the effects of original design and present practice differed substantially. Finally, Study 3 revealed that, within domains, the effects of original design and present practice depend on which entities design and use items. These results reveal striking similarities in purpose attributions across domains and suggest that certain entities are treated as authorities over the purposes of particular items. (shrink)

The rapid development in healthcare technologies in recent years has resulted in the need for health services, whether publicly funded or insurance based, to identify means to maximise the benefits and provide equitable distribution of limited resources. This has resulted in the need for rationing decisions, and there has been considerable debate regarding the substantive and procedural ethical principles that promote distributive justice when making such decisions. In this paper, I argue that while the scientifically rigorous approaches of evidence-based healthcare (...) are claimed as aspects of procedural justice that legitimise such guidance, there are biases and distortions in all aspects of the process that may lead to epistemic injustices. Regardless of adherence to principles of distributive justice in the decision-making process, evidential failings may undermine the fairness and legitimacy of such decisions. In particular, I identify epistemic exclusion that denies certain patient and professional groups the opportunity to contribute to the epistemic endeavour. This occurs at all stages of the process, from the generation, analysis and reporting of the underlying evidence, through the interpretation of such evidence, to the decision-making that determines access to healthcare resources. I further argue that this is compounded by processes which confer unwarranted epistemic privilege on experts in relation to explicit or implicit value judgements, which are not within their remit. I suggest a number of areas in which changes to the processes for developing, regulating, reporting and evaluating evidence may improve the legitimacy of such processes. (shrink)

Many healthcare agencies are producing evidence-based guidance and policy that may determine the availability of particular healthcare products and procedures, effectively rationing aspects of healthcare. They claim legitimacy for their decisions through reference to evidence-based scientific method and the implementation of just decision-making procedures, often citing the criteria of ‘accountability for reasonableness’; publicity, relevance, challenge and revision, and regulation. Central to most decision methods are estimates of gains in quality-adjusted life-years, a measure that combines the length and quality of survival. (...) However, all agree that the QALY alone is not a sufficient measure of all relevant aspects of potential healthcare benefits, and a number of value assessment frameworks have been suggested. I argue that the practical implementation of these procedures has the potential to lead to a distorted assessment of value. Undue weight may be ascribed to certain attributes, particularly those that favour commercial or political interests, while other attributes that are highly valued by society, particularly those related to care processes, may be omitted or undervalued. This may be compounded by a lack of transparency to relevant stakeholders, resulting in an inability for them to participate in, or challenge, the decisions. The makes it likely that costly new technologies, for which inflated prices can be justified by the current value frameworks, are displacing aspects of healthcare that are highly valued by society. (shrink)

In this book, 34 renowned philosophical practitioners from 20 different countries present a variety of dialogue methods for philosophical practice, which have never before been published in such a compact and compiled form. By having Socrates and his method of maieutics (the art of midwifery of the soul, as he called it) as one of its main sources of inspiration, the book offers different methodological approaches in order to prompt people to wonder, to reflect, to change perspective, and to think (...) differently; in short, to make people philosophize about life and the way they live it. (Series: Report of the Global Ethic Initiative Austria / Schriftenreihe der Initiative Weltethos Osterreich - Vol. 9) [Subject: Philosophy]. (shrink)

Spinoza's Theological-Political Treatise is one of the most important philosophical works of the early modern period. In it Spinoza discusses at length the historical circumstances of the composition and transmission of the Bible, demonstrating the fallibility of both its authors and its interpreters. He argues that free enquiry is not only consistent with the security and prosperity of a state but actually essential to them, and that such freedom flourishes best in a democratic and republican state in which individuals are (...) left free while religious organizations are subordinated to the secular power. His Treatise has profoundly influenced the subsequent history of political thought, Enlightenment 'clandestine' or radical philosophy, Bible hermeneutics, and textual criticism more generally. It is presented here in a translation of great clarity and accuracy by Michael Silverthorne and Jonathan Israel, with a substantial historical and philosophical introduction by Jonathan Israel. (shrink)

Theories of discourse bring to realism new ideas about how knowledge develops and how representations of reality are influenced. We gain an understanding of the conceptual aspect of social life and the processes by which meaning is produced. This collection reflects the growing interest realist critics have shown towards forms of discourse theory and deconstruction. The diverse range of contributions address such issues as the work of Derrida and deconstruction, discourse theory, Eurocentrism and poststructuralism. What unites all of the contributions (...) is a sense that it is essential to provide a realist alternative to the hitherto dominance of social constructionism, hermeneutics and postmodernism, over many of the issues discussed. By developing a realist perspective the different authors attempt to embed discourse within the structured nature of the reality of the world. Realism can situate language, discourse and ideology within context specific, or 'causally efficacious' circumstances. Realism can help to uncover issues of power, representation, and subjectivity and how discursive and other social practices produce real effects. This can help us understand the manner in which social structures are reproduced through various forms of ideology and discourse. And by knowing this, we can start to address questions concerning human emancipation and how the world is to be transformed. (shrink)

This paper responds to the commentaries from Stacy Carter and Alan Cribb. We pick up on two main themes in our response. First, we reflect on how the process of setting standards for empirical bioethics research entails drawing boundaries around what research counts as empirical bioethics research, and we discuss whether the standards agreed in the consensus process draw these boundaries correctly. Second, we expand on the discussion in the original paper of the role and significance of the concept of (...) ‘integrating’ empirical methods and ethical argument as a standard for research practice within empirical bioethics. (shrink)