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)

Holobionts are multicellular eukaryotes with multiple species of persistent symbionts. They are not individuals in the genetic sense— composed of and regulated by the same genome—but they are anatomical, physiological, developmental, immunological, and evolutionary units, evolved from a shared relationship between different species. We argue that many of the interactions between human and microbiota symbionts and the reproductive process of a new holobiont are best understood as instances of reciprocal scaffolding of developmental processes and mutual construction of developmental, ecological, and (...) evolutionary niches. Our examples show that mother, fetus, and different symbiotic microbial communities induce or constitute conditions for the development and reproduction of one another. These include the direct induction of maternal or fetus physiological changes, the restructuring of ecological relations between communities, and evolutionary selection against undesirable competitors. The mutual scaffolding and niche constructing processes start early—prior to amniotic rupture. We are evolutionarily, physiologically, and developmentally integrated holobiont systems, strung together through mutual reliance and mutual construction. Bringing the processes of niche construction and developmental scaffolding together to interpret holobiont birth conceptually scaffolds two new directions for research: in niche construction, identifying the evolutionary implications of organisms actively constructing multiple overlapping niches and scaffolds, and in Evolutionary Developmental Biology, characterizing evolutionary and ecological processes as developmental causes. (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)

: "Clinical pragmatism" is an important new method of moral problem solving in clinical practice. This method draws on the pragmatic philosophy of John Dewey and recommends an experimental approach to solving moral problems in clinical practice. Although the method may shed some light on how clinicians and their patients ought to interact when moral problems are at hand, it nonetheless is deficient in a number of respects. Clinical pragmatism fails to explain adequately how moral problems can be solved experimentally, (...) it underestimates the relevance and importance of judgment in clinical ethics, and it presents a questionable account of the role that moral principles should play in moral problem solving. (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)

Usage-based linguistics postulates that multi-word expressions constitute a substantial part of language structure and use, and are formed through repeated chunking and stored as exemplar wholes. They are also re-used to produce new sequences by means of schematization. While there is extensive research on multi-word expressions in many spoken languages, little is known about the status of multi-word expressions in the mainstream U.S. variety of American Sign Language. This paper investigates recurring multi-word expressions, or sequences of multiple signs, that involve (...) a high-frequency sign of visual perception glossed as look and the family of ‘look’ signs. The look sign exhibits two broad functions: look/‘vision’ references literal or metaphorical vision and look/‘reaction’ signals a person’s reaction to a visual stimulus. Data analysis reveals that there are recurring sequences in distinct syntactic environments associated with the two functions of look, suggesting that look is in the process of grammaticalization from a verb of visual perception to a stance verb. The sequences demonstrate the emergence of linguistic structure from repeated use through the domain-general cognitive process of chunking in ASL. (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)

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)

Abstract:This essay reviews the 2013 Human Life International (HLI) propaganda video, Central America and Mexico: Fighting for Life, Faith, and Family, which, we argue, illustrates the well-orchestrated counteroffensive against reproductive and sexual rights movements occurring in the region. First we summarize the film's key themes, including the assertion that Catholicism is fundamental to Mexican and Central American identities and that the international “pro-abortion movement” is waging war against Catholics. Second, we note the development of a new strategic alliance between Catholics (...) and evangelicals that relies on lay religious activists working in the fields of medicine, bioethics, law, and government. Third, we show how the video appeals to HLI donors by asking them to support crisis pregnancy centres, homes for unwed mothers, adoption programs, and “natural” fertility assistance. We argue that the film conspicuously ignores the consequences of abortion bans already in place in Nicaragua, El Salvador, and Honduras, and does not consider that what it terms “international pressures” also includes treaty obligations with the United Nations and Organization of American States. This essay offers insights into the strategies used by opponents of reproductive and sexual rights movements in Mexico and Central America. (shrink)