Rare copy number variants have a prominent role in the aetiology of schizophrenia and other neuropsychiatric disorders. Substantial risk for schizophrenia is conferred by large CNVs at several loci, including microdeletions at 1q21.1, 3q29, 15q13.3 and 22q11.2 and microduplication at 16p11.2. However, these CNVs collectively account for a small fraction of cases, and the relevant genes and neurobiological mechanisms are not well understood. Here we performed a large two-stage genome-wide scan of rare CNVs and report the significant association of copy (...) number gains at chromosome 7q36.3 with schizophrenia. Microduplications with variable breakpoints occurred within a 362-kilobase region and were detected in 29 of 8,290 patients versus 2 of 7,431 controls in the combined sample. All duplications overlapped or were located within 89 kilobases upstream of the vasoactive intestinal peptide receptor gene VIPR2. VIPR2 transcription and cyclic-AMP signalling were significantly increased in cultured lymphocytes from patients with microduplications of 7q36.3. These findings implicate altered vasoactive intestinal peptide signalling in the pathogenesis of schizophrenia and indicate the VPAC2 receptor as a potential target for the development of new antipsychotic drugs. © 2011 Macmillan Publishers Limited. All rights reserved. (shrink)

How do engineers respond to ethical dilemmas that occur in practice? How do they view their individual and collective responsibilities? How do they make decisions before all the facts are in? Using the space shuttle programme as the framework, this book examines the role of ethical decision making in the practice of engineering. In particular, the book considers the design and development of the main engines of the space shuttle as a paradigm for how individual engineers perceive, articulate, and resolve (...) ethical dilemmas in a large, complex organisation. A series of in-depth case studies show engineers at work on various stages of the project as they balance budgets, deadlines and risks. By documenting the historical development of a single system, the book provides a unique opportunity to explore the complex interactions between political, organisational and technical pressures and engineering and management decisions. (shrink)

We generalize the Unstable Formula Theorem characterization of stable theories from Shelah [11], that a theory T is stable just in case any infinite indiscernible sequence in a model of T is an indiscernible set. We use a generalized form of indiscernibles from [11], in our notation, a sequence of parameters from an L-structure M, , indexed by an L′-structure I is L′-generalized indiscernible inM if qftpL′=qftpL′ implies tpL=tpL for all same-length, finite ¯,j from I. Let Tg be the theory (...) of linearly ordered graphs in the language with signature Lg={<,R}. Let Kg be the class of all finite models of Tg. We show that a theory T has NIP if and only if any Lg-generalized indiscernible in a model of T indexed by an Lg-structure with age equal to Kg is an indiscernible sequence. (shrink)

The allocation of vaccines and therapeutics for Covid‐19 obviously raises ethical questions, and physicians and ethicists have begun to address them. Writers have identified various criteria that should guide allocation decisions, but the criteria often conflict and need to be balanced against one another. This article proposes a model for thinking about how different considerations that are relevant to the distribution of vaccines and scarce treatments for Covid‐19 could be integrated into an allocation procedure. The model employs the construct of (...) a weighted lottery, which is a construct that has been employed in other contexts that involve the distribution of scarce resources. The article highlights the advantages of applying a weighted lottery to the Covid‐19 context and offers an illustration for how it might work in practice. The primary aim of the article is to articulate the structural features of a weighted lottery for this context and to bring out its advantages over other methods for allocating Covid‐19 medications. (shrink)

The ethical standards that regulate clinical research have multiple rationales. Among them is the need to protect potential subjects from making imprudent decisions, which extends beyond the soft paternalistic concern to protect people from making uninformed decisions to participate in trials. This article argues that a plausible risk/benefit restriction on clinical trials is presumptively justified by hard paternalism, which in turn is supported by a deeper fairness-based rationale. This presumptive case for hard paternalism in research is not defeated by the (...) alleged right to participate in clinical trials, by concerns about insult or status, by the need to conduct early phase trials that promise little to no benefit to participants, or by the recognition that some potential subjects are altruistically motivated. (shrink)

In this paper, we defend the ethics of clinical research against the charge of paternalism. We do so not by denying that the ethics of clinical research is paternalistic, but rather by defending the legitimacy of paternalism in this context. Our aim is not to defend any particular set of paternalistic restrictions, but rather to make a general case for the permissibility of paternalistic restrictions in this context. Specifically, we argue that there is no basic liberty-right to participate in clinical (...) research and that considerations of distributive fairness justify some paternalistic protections of research subjects. (shrink)

US livestock agriculture hasdeveloped and intensified according to a strictproductionist model that emphasizes industrialefficiency. Sustainability problems associatedwith this model have become increasinglyevident and more contested. Traditionalapproaches to promoting sustainable agriculturehave emphasized education and outreach toencourage on-farm adoption of alternativeproduction systems. Such efforts build on anunderlying assumption that farmers areempowered to make decisions regarding theorganization and management of theiroperations. However, as vertical coordinationin agriculture continues, especially in theanimal agriculture sectors, this assumptionbecomes less valid. This paper examines how thechanging industrial structure in (...) four USlivestock sectors (poultry, hogs, beef, anddairy) affects possibilities in each forpromoting more sustainable productionpractices. Comparisons between the sectors arebased on the relative ability to employ anintensive pasture or alternative (deep-bedded)housing system, which are widely seen assustainable livestock alternatives. While thehighly integrated poultry sector appearsimpregnable to traditional sustainableagriculture approaches, the cow-calf sub-sectorof the beef industry, non-feedlot dairyoperations, and small parts of the hogindustry, especially in the Midwest, stillretain some potential for effectively targetingthe farmer. Building on the presentation ofbarriers and opportunities in the fourlivestock sectors, the paper concludes byevaluating several structurally-orientedapproaches to promoting a more sustainablelivestock agriculture that should complementmore traditional approaches. They includedeveloping alternative coordinated networks inlivestock agriculture, pressing integrators topermit more sustainable production practices,and working for legislation that shifts moredecision-making within integrated systemstowards growers. (shrink)

For a long time, linguists more or less denied the existence of individual differences in grammatical knowledge. While recent years have seen an explosion of research on individual differences, most usage-based research has failed to address this issue and has remained reluctant to study the synergy between individual and community grammars. This paper focuses on individual differences in linguistic knowledge and processing, and examines how these differences can be integrated into a more comprehensive constructionist theory of grammar. The examination is (...) guided by the various challenges and opportunities that may be extracted from scattered research that exists across disciplines touching on these matters, while also presenting some new data that illustrate how differentiation between individuals can improve models of long-term language change. The paper also serves as the introduction to this special issue of Cognitive Linguistics, which collects seven contributions from various linguistic disciplines focusing on key aspects of individuals’ grammars. (shrink)

In light of the widespread existence of financial and non-financial issues that contribute to the appearance or fact of conflict of interest, it is proposed that conflict of interest should generally be assumed, no matter the source of financial support or the expressed declarations of conflicts and even with respect to one’s own work. No new model is advanced for modification of peer-review processes or for elaboration of author declarations of interest. Researchers should be assessing the quality of published work (...) as best they can and make their own decisions on the appropriate use of the work. While some apparent sources of conflict are likely more obvious and serious than others, even subtler biases can influence scientific reports. Ignoring peer-reviewed contributions because of conflict-of-interest concerns is discouraged. Listening skeptically to all sources, including yourself, is encouraged. (shrink)

Drawing the line on physician assistance in physician-assisted death (PAD) continues to be a contentious issue in many legal jurisdictions across the USA, Canada and Europe. PAD is a medical practice that occurs when physicians either prescribe or administer lethal medication to their patients. As more legal jurisdictions establish PAD for at least some class of patients, the question of the proper scope of this practice has become pressing. This paper presents an argument for restricting PAD to the terminally ill (...) that can be accepted by defenders as well as critics of PAD for the terminally ill. The argument appeals to fairness-based paternalism and the social meaning of medical practice. These two considerations interact in various ways, as the paper explains. The right way to think about the social meaning of medical practice bears on fair paternalism as it relates to PAD and vice versa. The paper contends that these considerations have substantial force when directed against proposals to extend PAD to non-terminally ill patients, but considerably less force when directed against PAD for the terminally ill. The paper pays special attention to the case of non-terminally ill patients who suffer from treatment-resistant depression, as these patients present a potentially strong case for extending PAD beyond the terminally ill. (shrink)

The concept of “public participation” is currently one of great interest to researchers and policy makers. In response to a perceived need for greater public involvement in decision making and policy formation processes on the part of both policymakers and the general public, a variety of novel mechanisms have been developed, such as the consensus conference and citizens jury, to complement traditional mechanisms, such as the public meeting. However, the relative effectiveness of the various mechanisms is unclear, as efforts at (...) evaluation have been sparse. In this article, the authors describe an evaluation of a two-day “deliberative conference” on the topic of radiation dose assessment. The authors detail the evaluation framework that they adopt and describe the instruments that they have developed to determine the attainment of the evaluationcriteria stipulated in that framework. They then describe the participation exercise that they have evaluated. Finally, they apply the instruments to assess the effectiveness of the exercise, and discuss the results and their implications for the conduct of evaluations and the use of this particular participation mechanism. (shrink)

Recent years have witnessed a growing concern that terminally illpatients are needlessly suffering in the dying process. This has ledto demands that physicians become more attentive in the assessment ofsuffering and that they treat their patients as `whole persons.'' Forthe most part, these demands have not fallen on deaf ears. It is nowwidely accepted that the relief of suffering is one of the fundamentalgoals of medicine. Without question this is a positive development.However, while the importance of treating suffering has generally (...) beenacknowledged, insufficient attention has been paid to the question ofwhether different types of terminal suffering require differnt responsesfrom health care professionals. In this paper we introduce a distinctionbetween two types of suffering likely to be present at the end of life,and we argue that physicians must distinguish between these types if theyare to respond appropriately to the suffering of their terminally illpatients. After introducing this distinction and explaining its basis,we further argue that the distinction informs a (novel) principle ofproportionality, one that should guide physicians in balancing theircompeting obligations in responding to terminal suffering. As weexplain, this principle is justified by reference to the intereststerminally ill patients have in restoration, as well as in therelief of suffering, at the end of life. (shrink)

Building on developments in feminist science scholarship and the philosophy of science, I advocate two methodological principles as elements of a naturalized philosophy of science. One principle incorporates a holistic account of evidence inclusive of claims and theories informed by and/or expressive of politics and non-constitutive values; the second takes communities, rather than individual scientists, to be the primary loci of scientific knowledge. I use case studies to demonstrate that these methodological principles satisfy three criteria for naturalization accepted in naturalized (...) philosophy of science, and allow for the differential assessment of episodes in which values and sociopolitical factors inform, or contribute to the adoption of, theories for which there is sufficient evidential warrant — and episodes in which such factors inform, or contribute to the adoption of, theories for which there is not. I contend that in terms of their empirical and normative import, these principles constitute a further naturalization of the philosophy of science. (shrink)

Recent studies lead to the paradoxical conclusion that the act of affirming one's egalitarian or prosocial values and virtues might subsequently facilitate prejudiced or self-serving behavior, an effect previously referred to as ?moral credentialing.? The present study extends this paradox to the domain of academic misconduct and investigates the hypothesis that such an effect might be limited by the extent to which misbehavior is rationalizable. Using a paradigm designed to investigate deliberative and rationalized forms of cheating (von Hippel, Lakin, & (...) Shakarchi, 2005), we found that when participants had credentialed themselves (vs. a nonclose acquaintance) via a set of hypothetical moral dilemmas, they were more likely to cheat on a subsequent math task, but only if cheating was highly rationalizable. When cheating was difficult to rationalize, moral credentialing had almost no impact on cheating. (shrink)

Some commentators have recently proposed that “clinical equipoise,” although widely accepted, is not necessary for morally acceptable research on human subjects. If this concept is rejected, however, we may find that trials not in the best medical interests of their subjects—”bad deal trials”—could be justified. To avoid exploiting participants, we must find a way to distribute the risks fairly, even if it means embracing radical changes in the way clinical research is conducted.

Scholars in the early seventeenth century who studied ancient Greek scientific theories often drew upon philology and history to reconstruct a more general picture of the Greek past. Gassendi's training as a humanist historiographer enabled him to formulate a conception of the history of philosophy in which the rationality of scientific and philosophical inquiry depended on the historical justifications which he developed for his beliefs. Professor Joy examines this conception and analyzes the nature of Gassendi's historical training, especially its relationship (...) to his career as a physicist and astronomer. She shows how he rehabilitated Epicurean atomism by bringing together the arguments of the Greek atomists and those of his contemporaries. In doing so, he produced an account of the natural world which made it an object of empirical study and mechanical explanation. (shrink)

Temporary labour migration programs are often proposed as a way to provide the benefits of migration in general, while mitigating the allegedly problematic effects of permanent migration. Here I propose that the arguments deployed in favour of temporary labour migration over permanent migration are flawed, normatively, and that empirically temporary labour migration programs produce effects in receiving states that are even worse than those (allegedly) produced by permanent migration. As a result, I shall argue that, for reasons of consistency, advocates (...) of restricting permanent migration should support restricting temporary labour migration programs as well. I conclude not by arguing that temporary labour migration programs should be abandoned, but rather that we must focus more seriously on re-constructing temporary labour migration programs that do not produce these dilemmas, as well as on generating policies that alleviate the challenges they often pose in receiving societies. (shrink)

This article critically analyzes the principle of beneficence and the principle of nonmaleficence in clinical medical ethics. It resists some recent skepticism about the principle of nonmaleficence, and then seeks to explain its role in medicine. The article proposes that the two principles are informed by different accounts of what is in the patient’s best interests. The principle of beneficence is tied to the patient’s best overall interests, whereas the principle of nonmaleficence is tied to the patient’s best medical interests (...) only. The article argues that the principle of nonmaleficence takes priority over the principle of beneficence in that it filters the treatment options that are appropriately subject to the principle of beneficence. Understanding how both principles can play an important role in medical practice, and how they relate when they come into conflict, can help clinicians to avoid certain mistakes in thinking about their duties to their patients. (shrink)

This paper suggests that the appearance of circularity in descartes' arguments is due to a lack of precision in his statements of them, Rather than to any flaw in his reasoning. The clear and distinct perceptions presupposed in the demonstrations of the existence of God are not the same as those whose reliability depends upon the existence of god. He is presupposing the reliability only of those clear and distinct perceptions which are known through the light of nature and have (...) metaphysical certainty in that they cannot be imagined false even on the demon hypothesis. And the only clear and distinct perceptions whose reliability he is demonstrating are those which are not known through the light of nature with metaphysical certainty but are subject to metaphysical doubt on the demon hypothesis, Even though they have moral or psychological certainty. (shrink)

A distressing number of philosophers and classicists think that the deuteros plous or “second best” mentioned at Phaedo 99c9-dl is the hypothetical method. Many of them will even tell you that Plato says the hypothetical method is the deuteros plous, and that they are not merely interpreting his meaning. They usually back off, however, when challenged on this point, for there jus isn’t any such statement by Plato. Nor, I think, does Plato give us any justification at all for taking (...) the deuteros plous as the hypothetical method. I will argue in this paper that he is referring rather to the explanation of things in terms of their formal causes, and that this sort of explanation is “second best” when compared to a teleological explanation in terms of final causes. The hypothetical method of the dialectician is simply the logical device or apparatus by means of which the theory of ideas and the attendant notion of formal causation are introduced into the discussion; it is not a “second best” method and is not inferior to anything else. (shrink)

Ethical research on human subjects requires that subjects, if they have the capacity to do so, give free and informed consent to participate in the trials in which they are enrolled. This requirement, which is commonly referred to as the principle of informed consent, was prominently endorsed by the authors of the Belmont Report in 1978, and it remains widely accepted today. Yet while the principle of informed consent is by now almost universally accepted, the responsibilities that it imposes on (...) those who conduct research on human subjects is a more contentious matter. New challenges to securing informed consent have emerged since the publication of the Belmont Report, and responding to these challenges requires... (shrink)

We compared study characteristics of randomized controlled trials funded by industry (N=697) to those not funded by industry (N=835). RCTs published in high-impact journals are more likely to be blinded, more likely to include a placebo, and more likely to post trial results on ClinicalTrials.gov. Our findings emphasize the importance of evaluating the quality of an RCT based on its methodological rigor, not its funder type.

In diesem Beitrag wollen wir zeigen, wieso die Fachdidaktik Philosophie und Ethik (neue) Ansätze entwickeln muss, um dem Anspruch auf (philosophische) Bildung von Menschen mit sonderpädagogischem Förderbedarf gerecht zu werden. Dafür zeigen wir anhand von Schüler_innen mit eingeschränkten Kommunikationsmöglichkeiten auf, wie Philosophieren mit ihnen dennoch möglich ist. Gleichzeitig wenden wir uns im Beitrag dem Haupteinwand zu, der darin besteht, dass Philosophieren mit dieser Schüler_innengruppe nicht möglich sei. Wir erklären unter welchen Umständen dieser Einwand nicht aufrecht erhalten werden sollte, sondern vielmehr (...) eine moralische Pflicht besteht, Menschen mit Behinderung philosophische Bildungsprozesse zu ermöglichen. (shrink)

This paper is part of an ongoing study that looks at the development of one component of a community network in a city in upstate New York. ‘Community networks’ refers to the use of computer networking technologies for the benefit of strengthening community goals and needs. The component studied is a youth database. In particular, this article looks at the early phases of this project: how the idea of the database emerged, how the technology was presented to the community, and (...) the community's response to this project. Theories guiding this paper include the social construction of technology theory and social worlds theory. (shrink)

Contemporary law and public policy often treat human beings as selfish creatures who respond only to punishments and rewards. Yet every day we behave unselfishly--few of us mug the elderly or steal the paper from our neighbor's yard, and many of us go out of our way to help strangers. We nevertheless overlook our own good behavior and fixate on the bad things people do and how we can stop them. In this pathbreaking book, acclaimed law and economics scholar (...) class='Hi'>Lynn Stout argues that this focus neglects the crucial role our better impulses could play in society. Rather than lean on the power of greed to shape laws and human behavior, Stout contends that we should rely on the force of conscience. Stout makes the compelling case that conscience is neither a rare nor quirky phenomenon, but a vital force woven into our daily lives. Drawing from social psychology, behavioral economics, and evolutionary biology, Stout demonstrates how social cues--instructions from authorities, ideas about others' selfishness and unselfishness, and beliefs about benefits to others--have a powerful role in triggering unselfish behavior. Stout illustrates how our legal system can use these social cues to craft better laws that encourage more unselfish, ethical behavior in many realms, including politics and business. Stout also shows how our current emphasis on self-interest and incentives may have contributed to the catastrophic political missteps and financial scandals of recent memory by encouraging corrupt and selfish actions, and undermining society's collective moral compass. This book proves that if we care about effective laws and civilized society, the powers of conscience are simply too important for us to ignore. (shrink)

Purpose Recent research has found unrealistic optimism among patient-subjects in early-phase oncology trials. Our aim was to investigate the cognitive and motivational factors that evoke this bias in this context. We expected perceptions of control to be a strong correlate of unrealistic optimism. Methods A study of patient-subjects enrolled in early-phase oncology trials was conducted at two sites in the USA. Respondents completed questionnaires designed to assess unrealistic optimism and several risk attribute variables that have been found to evoke the (...) bias in other contexts. Results One hundred and seventy-one patient-subjects agreed to be interviewed for our study. Significant levels of perceived controllability were found with respect to all nine research-related questions. Perceptions of control were found to predict unrealistic optimism. Two other risk attribute variables, awareness of indicators and mental image, were correlated with unrealistic optimism. However, in multivariate regression analysis, awareness and mental image dropped out of the model and perceived controllability was the only factor independently associated with unrealistic optimism. Conclusion Patient-subjects reported that they can, at least partially, control the benefits they receive from participating in an early-phase oncology trial. This sense of control may underlie unrealistic optimism about benefiting personally from trial participation. Effective interventions to counteract unrealistic optimism may need to address the psychological factors that give rise to distorted risk/benefit processing. (shrink)

Professor Copi provides us with the following example:Remove all cards except aces and kings from a deck, so that only eight cards remain, of which four are aces and four are kings. From this abbreviated deck, deal two cards to a friend. If he looks at his cards and announces that his hand contains an ace, what is the probability that both his cards are aces? If he announces instead that one of his cards is the ace of spades, what (...) is the probability then that both his cards are aces? (shrink)

In recent years, a number of writers have proposed voluntary stopping of eating and drinking as an alternative to physician-assisted suicide. This paper calls attention to and discusses some of the ethical complications that surround the practice of voluntary stopping of eating and drinking. The paper argues that voluntary stopping of eating and drinking raises very difficult ethical questions. These questions center on the moral responsibility of clinicians who care for the terminally ill as well as the nature and limits (...) of the authority they exercise over them. (shrink)

We are currently in the midst of a revival of interest in thevirtues. A number of contemporary moral philosophers havedefended a virtue-based approach to ethics. But does thisrenewal of interest in the virtues have much to contributeto medical ethics and medical practice? This paper criticallydiscusses this question. It considers and rejects a number ofimportant arguments that purport to establish the significanceof the virtues for medical practice. Against these arguments,the paper seeks to show that while the virtues have a genuinerole to (...) play in medical ethics, it is a limited role, one thatis subordinate to the role that other moral concepts such asrules and principles play. (shrink)

The "divided line" passage seems to compare the four states of the soul and their objects to the four segments of a line, somewhat as follows.

The European Legacy, Volume 17, Issue 4, Page 562-563, July 2012.

This is the first musicological study entirely devoted to a comprehensive analysis of musical Holocaust representations in the Western art music tradition. Through a series of chronological case studies grounded in primary source analysis, Amy Lynn Wlodarski analyses the compositional processes and conceptual frameworks that provide key pieces with their unique representational structures and critical receptions. The study examines works composed in a variety of musical languages - from Arnold Schoenberg's dodecaphonic A Survivor from Warsaw to Steve Reich's minimalist (...) Different Trains - and situates them within interdisciplinary discussions about the aesthetics and ethics of artistic witness. At the heart of this book are important questions about how music interacts with language and history; memory and trauma; and politics and mourning. Wlodarski's detailed musical and cultural analyses provide new models for the assessment of the genre, illustrating the benefits and consequences of musical Holocaust representation in the second half of the twentieth century. (shrink)

This study compares involuntary and voluntary autobiographical memories in depressed and never depressed individuals. Twenty depressed and twenty never depressed individuals completed a memory diary; recording their reactions to 10 involuntary and 10 voluntary memories over 14–30 days. Psychiatric status , psychopathology, rumination and avoidance were assessed. For both groups, involuntary memories more frequently lead to strong reactions than voluntarily memories. For both modes of retrieval, depressed individuals reported more frequent negative reactions than never depressed individuals and rated memories as (...) more central to identity with higher levels of rumination and avoidance. Depressed individuals retrieved both positive and negative memories during involuntary retrieval. These findings support the view that involuntary memory retrieval represents a basic mode of retrieval during healthy and disordered cognition, and that during depression, both involuntary and voluntary memories are central to identity and associated with rumination and avoidance. (shrink)