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)

INTRODUCTION Reopening a Discussion The empiricist-derived epistemology that has directed most social and natural scientific inquiry for the last three ...

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)

Feminism, Science, and the Philosophy of Science brings together original essays by both feminist and mainstream philosophers of science that examine issues at the intersections of feminism, science, and the philosophy of science. Contributors explore parallels and tensions between feminist approaches to science and other approaches in the philosophy of science and more general science studies. In so doing, they explore notions at the heart of the philosophy of science, including the nature of objectivity, truth, evidence, cognitive agency, scientific method, (...) and the relationship between science and values. (shrink)

The relationship between ethics and economics has never been easy. Opponents in a tug of war, friends in a warm embrace, ships passing in the night—the relationship has been highly variable. In recent years, the friendship model has been gaining credence, particularly among U.S. corporate executives. Increasingly, companies are launching ethics programs, values initiatives, and community involvement activities premised on management’s belief that “Ethics pays.”.

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 juxtaposition encompassed in the phrase "feminist epistemology" strikes some feminist theorists and mainstream epistemologists as incongruous. To others, the phrase signals the view that epistemology and the philosophy of science are not what some of their practitioners and advocates have wanted or claimed them to be-but also are not "dead," as some of their critics proclaim. This essay explores the grounds for and implications of each view and recommends the second.

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)

Brentano's philosophy of art, contained primarily in his book, Grundzuge der Ästhetik, is the result of an original theory of intrinsic value that was derived from Brentano's philosophical psychology. In his aesthetics, Brentano endeavored to find an objective ground for the value of aesthetic contemplation through his theory of the intentional objects of emotions and desires. The lack of attention Brentano's aesthetics has received is surprising, given that two of the many students Brentano influenced, Husserl (through the development of the (...) phenomenological movement) and Ehrenfels (through the development of Gestalt psychology) have had an extraordinary influence on twentieth century perceptions of art. In this paper I will attempt to redress some of this neglect by outlining Brentano's analysis of aesthetic intentions and the relationship his aesthetics bears to his overall philosophical system. (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)

We consider Helen Longino's proposal that "ontological heterogeneity", "complexity of relationship", and "the non-disappearance of gender" are criteria for good science and cannot be separated into cognitive and social virtues. Using a research program in neuroendocrinology investigating a hormonal basis for sex-differentiated lateralization as a case study, the authors disagree concerning whether the first two criteria can be construed as criteria for good science. Concerning the non-disappearance of gender criterion, we argue that its appropriateness is context specific, and that its (...) cognitive and social formulations are separable and should be construed as such. (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)

This essay critiques feminist treatments of maternal-fetal "relationality" that unwittingly replicate features of Western individualism (for example, the Cartesian division between the asocial body and the social-cognitive person, or the conflation of social and biological birth). I argue for a more reflexive perspective on relationality that would acknowledge how we produce persons through our actions and rhetoric. Personhood and relationality can be better analyzed as dynamic, negotiated qualities realized through social practice.

The term “exploitation” has gained wide currency in recent discussions of biomedical and research ethics. This is due in no small measure to the influence of Alan Wertheimer’s path-breaking work on the topic (Wertheimer 1999, 2011). Wertheimer presented a clear and compelling non-Marxist account of the concept of exploitation—one that stressed the connection between exploitation and unfair distributive outcomes. On this account, when one party exploits another, she takes advantage of the other to gain unfairly. A number of contemporary bioethicists (...) have accepted Wertheimer’s account of exploitation and have proceeded to apply it to a range of issues in research ethics (Hawkins and Emanuel 2008; Miller and Brody .. (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)

Recent empirical work on the concept of intentionality suggests that people’s assessments of whether an action is intentional are subject to uncertainty. Some researchers have gone so far as to claim that different people employ different concepts of intentional action. These possibilities have motivated a good deal of work in the relatively new field of experimental philosophy. The findings from this empirical research may prove to be relevant to medical ethics. In this article, we address this issue head on. We (...) first describe a study we conducted on intention ascription. Drawing on recent work in experimental philosophy, we investigated the possibility that the ascription of intentions to clinical actors in clinical settings is influenced by prior judgments about the goodness or badness of the consequences of the action in question. Our study was modeled on experimental studies in other contexts that have shown that people, when presented with a range of scenarios, are more likely to classify a side effect of an action as intended if the side effect is negative or reflects poorly on the actor than if it is positive or reflects well on the actor. We investigated whether this asymmetry in intention ascriptions was also present among physicians who were asked to ascribe intentions to clinical actors in certain well-defined clinical scenarios. After describing the study and its results, we discuss its implications for medical ethics. (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)

This chapter contains sections titled: Highlights of Past Literature Current Work Future Work.

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)

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.