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)

In this paper, we discuss our approach to developing engaging course content linked to distinct learning outcomes on the topic of academic authorship. Academic authorship is a critical element of research culture and responsible conduct of research (RCR) courses. Drawing on instructional design methods, our online course aims to stimulate critical thinking about ethical authorship practices and to help students develop skills for resolving authorship-related conflicts. The course is scaffolded to facilitate engagement by tying video and podcast-style media, a choice-based (...) interactive simulation, and traditional case study activities, to specific learning objectives. We describe how each instructional technique enhances student engagement and learning for the paired objective, and the benefits of the holistic course design. Finally, we illustrate how RCR instructors can incorporate our materials in full or in part into their own course curricula and encourage others to use our course development approach when designing their own courses. (shrink)

We report the identification of a recurrent, 520-kb 16p12.1 microdeletion associated with childhood developmental delay. The microdeletion was detected in 20 of 11,873 cases compared with 2 of 8,540 controls and replicated in a second series of 22 of 9,254 cases compared with 6 of 6,299 controls. Most deletions were inherited, with carrier parents likely to manifest neuropsychiatric phenotypes compared to non-carrier parents. Probands were more likely to carry an additional large copy-number variant when compared to matched controls. The clinical (...) features of individuals with two mutations were distinct from and/or more severe than those of individuals carrying only the co-occurring mutation. Our data support a two-hit model in which the 16p12.1 microdeletion both predisposes to neuropsychiatric phenotypes as a single event and exacerbates neurodevelopmental phenotypes in association with other large deletions or duplications. Analysis of other microdeletions with variable expressivity indicates that this two-hit model might be more generally applicable to neuropsychiatric disease. © 2010 Nature America, Inc. All rights reserved. (shrink)

This bibliographical study involved first the exploitation of four data-banks: Medline, CNRS, Bioethics and AIDS, with the following key words (in conjunction with AIDS): ethics, human rights, confidentiality, legislation, jurisprudence. A total of 412 references were listed between 1983 and the end of 1987. Examination of the quantitative increase of articles over these years shows that, while references to AIDS and/or HIV infection--referred to as 'AIDS' for brevity--increased by about one third per year, the number of papers treating ethical (...) problems linked to AIDS doubled each year. This increase makes it clear that these problems are important and pressing, that they are evolving rapidly and can be given no easy solution. After reading and analysis of accessible articles in readily comprehensible languages, the different themes can be classified in two categories: 1: Measures intended to protect society (starting with the most coercive); quarantine and isolation; discriminatory measures concerning specific groups; non-respect of the confidential nature of medical information; application of the penal code; screening; obligatory declaration and registration; testing of blood given by donors; vaccination and medical innovations, therapeutic assays; information, education. 2. Measures intended to protect the individual: fundamental rights of the patient: his/her right to confidentiality, to information and to treatment; civil rights: civil liberty, right to education, right to work, etc...; rights of the healthy individual: right of those in contact with the patients, safety of hospital staff, of those receiving blood-transfusions, etc... The legislation adopted in the various countries and the main opinions to be found in these articles are listed and analysed, and for each particular theme it is possible to refer to a list of the 232 most important articles. While the debate seems to concentrate on the conflict between the right of society to protect itself against the spread of infection and the 'civil' rights of the infected minorities, our conclusion tends to reduce this antagonism, showing that, particularly as far as the confidential nature of medical information is concerned, measures intended to protect the individual also protect society. (shrink)

Increasingly the body is a possession that does not belong to us. It is bought and sold, bartered and stolen, marketed wholesale or in parts. The professions - especially reproductive medicine, transplant surgery, and bioethics but also journalism and other cultural specialists - have been pliant partners in this accelerating commodification of live and dead human organisms. Under the guise of healing or research, they have contributed to a new 'ethic of parts' for which the divisible body is severed from (...) the self, torn from the social fabric, and thrust into commercial transactions -- as organs, secretions, reproductive capacities, and tissues -- responding to the dictates of an incipiently global marketplace. Breaking with established approaches which prioritize the body as 'text', the chapters in this book examine not only images of the body-turned-merchandise but actually existing organisms considered at once as material entities, semi-magical tokens, symbolic vectors and founts of lived experience. The topics covered range from the cultural disposal and media treatment of corpses, the biopolitics of cells, sperm banks and eugenics, to the international trafficking of kidneys, the development of 'transplant tourism', to the idioms of corporeal exploitation among prizefighters as a limiting case of fleshly commodity. This insightful and arresting volume combines perspectives from anthropology, law, medicine, and sociology to offer compelling analyses of the concrete ways in which the body is made into a commodity and how its marketization in turn remakes social relations and cultural meanings. (shrink)

The complexity of biobank research raises concerns about individuals’ understanding of the information conveyed in the consent process for such research.. We report the results of a qualitative, cognitive interview study with an ethnically, linguistically, and educationally diverse sample of 43 respondents to assess the clarity and utility of a multimedia tool developed for a biobank. Using weighted randomization, respondents were assigned to either view the multimedia tool or read a written consent document . The study illustrates the utility of (...) cognitive interviews for gaining insights from prospective research participants about the clarity of informed consent tools. Findings suggest that a multimedia tool is useful for communicating key messages but should be combined with a written consent document and personal interaction with the study staff. We recommend that the potential value of multimedia tools should be more rigorously tested in a randomized controlled trial. (shrink)

The banker Pasion, father of the notorious fourth-century litigant and politician Apollodoros, some of whose speeches have survived under the name of Demosthenes, was originally a slave; freed by his owners, he made a substantial fortune from banking and subsequently received Athenian citizenship for his generous gifts to the city. At [Dem.] 59.2 we are given a paraphrase of the decree which enfranchised him: 'Aθηναον εναι Πασωνα κα κγνους τος κενου ‘[the Athenian people voted] that Pasion and his descendants should (...) be Athenian’. In common with inscriptions recording grants of citizenship, and unlike Roman military diplomata, the decree appears to have ignored Pasion's wife Archippe. The silence of the decrees of enfranchisement is echoed in the literary sources, with the result that we have no explicit testimony to the legal status of the wife of an alien who was granted Athenian citizenship. M. J. Osborne assumes that the status of the wife was in no way affected by the grant; she remained an alien. D. Whitehead has argued that in such cases the wife's status was indeterminate; in the event of the death of her first husband she might find herself married either to an Athenian citizen or to an alien, whereupon her status would be defined according to that of her husband. This article will argue that Archippe's status was unaffected by Pasion's receipt of citizenship, that is, that she remained a metic. I shall then proceed to consider the question of the implications of the difference in status of Pasion and Archippe subsequent to his enfranchisement for the legal basis of the relationship between them, and finally draw a tentative conclusion about the date of Pasion's receipt of citizenship. (shrink)

La financiarisation du marché est associée à un déficit démocratique, à un accroissement des inégalités et à un contexte mondial d’incertitude et de crises. Dans le présent article, nous revisitons les vues d’Adam Smith au xviiie siècle sur ces sujets, au-delà de sa caricature néolibérale. Nous suggérons que le père de l’économie moderne, sur qui l’on fonde l’idéologie de la « main invisible » en économie et le « laissez-faire » pour les entreprises, recommandait en fait l’instauration de régulations strictes (...) des banques et de la finance. Après avoir présenté les régulations que Smith a proposées en son temps, nous tirons de son œuvre plusieurs suggestions de réforme pour les secteurs bancaire et financier, contribuant ainsi au débat actuel sur ces questions, tout en l’enracinant dans son contexte historique. (shrink)

Mencius, who lived in the 4th century B.C., is second only to Confucius in importance in the Confucian tradition. The _Mencius_ consists of sayings of Mencius and conversations he had with his contemporaries. When read side by side with the _Analects_, the _Mencius_ throws a great deal of light on the teachings of ConfuciusMencius developed many of the ideas of Confucius and at the same time discussed problems not touched upon by Confucius. He drew out the implications of Confucius' moral (...) principles and reinterpreted them for the conditions of his time. As the fullest of the four great Confucian texts, the _Mencius_ has been the required reading amongst Chinese scholars for two thousand years, and it still throws considerable light on the character of the Chinese people. (shrink)

A record of the words and teachings of Confucius, _The Analects_ is considered the most reliable expression of Confucian thought. However, the original meaning of Confucius's teachings have been filtered and interpreted by the commentaries of Confucianists of later ages, particularly the Neo-Confucianists of the Song dynasty, not altogether without distortion.In this monumental translation by Professor D. C. Lau, an attempt has been made to interpret the sayings as they stand. The corpus of the sayings is taken as an organic (...) whole and the final test of the interpretation rests on the internal consistency it exhibits. In other words, _The Analects_ is read in the light of _The Analects._This results in a truer understanding of Confucius' thought than the traditional interpretation and paves the way for a re-assessment of its importance in the history of Chinese thought and its relevance to the present day world.This volume also contains an introduction to the life and teachings of Confucius, and three appendices on the events in the life of Confucius, on his disciples, and on the composition of _The Analects._. (shrink)

In over thirty lines of the Agamemnon I think I discern lurking in the apparatus of modern editions truths unnoticed by recent editors, and needing for the most part merely redivision, repunctuation, or reaccentuation to become recognizable. At a few points I offer alternative interpretations of readings that have been accepted by some at least among modern editors.

... the topic of 'meaning' is the one topic discussed in philosophy in which there is literally nothing but 'theory' - literally nothing that can be labelled or even ridiculed as the 'common sense view'. Putnam, 'The Meaning of Meaning' This book explores some truths behind the truism that experimentation is a hallmark of scientific activity. Scientists' descriptions of nature result from two sorts of encounter: they interact with each other and with nature. Philosophy of science has, by and large, (...) failed to give an account of either sort of interaction. Philosophers typically imagine that scientists observe, theorize and experiment in order to produce general knowledge of natural laws, knowledge which can be applied to generate new theories and technologies. This view bifurcates the scientist's world into an empirical world of pre-articulate experience and know how and another world of talk, thought and argument. Most received philosophies of science focus so exclusively on the literary world of representations that they cannot begin to address the philosophical problems arising from the interaction of these worlds: empirical access as a source of knowledge, meaning and reference, and of course, realism. This has placed the epistemological burden entirely on the predictive role of experiment because, it is argued, testing predictions is all that could show that scientists' theorizing is constrained by nature. Here a purely literary approach contributes to its own demise. The epistemological significance of experiment turns out to be a theoretical matter: cruciality depends on argument, not experiment. (shrink)

In recent years, the starting-dates of both the Historiae and the Annales of Tacitus have been criticized. In the case of the Historiae, Hainsworth has claimed that Tacitus chose to start his narrative with the events of A.D. 69, because for various reasons the events of A.D. 68 were an embarrassment to him. Syme has suggested, in the case of the Annales, that by starting with the accession of Tiberius, Tacitus has barred himself from a proper understanding of that principate.

_Rhetoric_ is the sixth volume in The New Hackett Aristotle series, a series featuring translations, with Introductions and Notes, by C. D. C. Reeve, Delta Kappa Epsilon Distinguished Professor of Philosophy at The University of North Carolina at Chapel Hill. The series will eventually include all of Aristotle's works.

In this paper we will offer a few examples to illustrate the orientation of contemporary research in data analysis and we will investigate the corresponding role of mathematics. We argue that the modus operandi of data analysis is implicitly based on the belief that if we have collected enough and sufficiently diverse data, we will be able to answer most relevant questions concerning the phenomenon itself. This is a methodological paradigm strongly related, but not limited to, biology, and we label (...) it the microarray paradigm. In this new framework, mathematics provides powerful techniques and general ideas which generate new computational tools. But it is missing any explicit isomorphism between a mathematical structure and the phenomenon under consideration. This methodology used in data analysis suggests the possibility of forecasting and analyzing without a structured and general understanding. This is the perspective we propose to call agnostic science, and we argue that, rather than diminishing or flattening the role of mathematics in science, the lack of isomorphisms with phenomena liberates mathematics, paradoxically making more likely the practical use of some of its most sophisticated ideas. (shrink)

Mencius, who lived in the 4th century B.C., is second only to Confucius in importance in the Confucian tradition. The _Mencius_ consists of sayings of Mencius and conversations he had with his contemporaries. When read side by side with the _Analects_, the _Mencius_ throws a great deal of light on the teachings of ConfuciusMencius developed many of the ideas of Confucius and at the same time discussed problems not touched upon by Confucius. He drew out the implications of Confucius' moral (...) principles and reinterpreted them for the conditions of his time. As the fullest of the four great Confucian texts, the _Mencius_ has been the required reading amongst Chinese scholars for two thousand years, and it still throws considerable light on the character of the Chinese people. (shrink)

This article discusses the adequacy of Rawls’ theory of justice as a tool for racial justice. It is argued that critics like Charles W Mills fail to appreciate both the insights and limits of the Rawlsian framework. The article has two main parts spread out over several different sections. The first is concerned with whether the Rawlsian framework suffices to prevent racial injustice. It is argued that there are reasons to doubt whether it does. The second part is concerned with (...) whether a Rawlsian framework has the resources to rectify past racial injustice. It is argued that it has more resources to do this than Mills allows. This second part of the article centers on two Rawlsian ideas: ideal theory and the fair equality of opportunity principle. It is argued that ideal theory is essential for the kind of rectificatory work that Mills wants nonideal theory to do, and that where there is a socioeconomic legacy of past injustice, it is hard to see how FEO could be implemented if it did no rectificatory work, a result which means that there is less need to turn to nonideal theory at all. (shrink)

This paper argues that the concept and role of ‘institutional racism’ in contemporary discussions of race should be reconsidered. It starts by distinguishing between ‘intrinsic institutional racism’, which holds that institutions are racist in virtue of their constitutive features, and ‘extrinsic institutional racism’, which holds that institutions are racist in virtue of their negative effects. It accepts intrinsic institutional racism, but argues that a ‘disparate impact’ conception of extrinsic conception faces a number of objections, the most serious being that it (...) has no plausible account of what it is that makes extrinsically racist institutions racist. It also argues that claims about the explanatory indispensability of institutional racism are overstated (individual racism is at least as important), critiques structural approaches to racial inequality, and suggests that there is reason to doubt whether institutional reform can provide us with all that morality may require in the racial domain. (shrink)