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.”.

SummaryA sample of 104 British parents with criminal convictions had an average fertility of 3·91 children as compared with 2·21 for the general population. The result suggests that fertility for criminal behaviour is dysgenic involving an increase in the genes underlying criminal behaviour in the population.

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)

Unrealistic optimism is a bias that leads people to believe, with respect to a specific event or hazard, that they are more likely to experience positive outcomes and/or less likely to experience negative outcomes than similar others. The phenomenon has been seen in a range of health-related contexts—including when prospective participants are presented with the risks and benefits of participating in a clinical trial. In order to test for the prevalence of unrealistic optimism among participants of early-phase oncology trials, we (...) conducted a survey with patients over 18 years of age who were enrolled in a phase I, phase I/II, or phase II clinical cancer trial in the New York City area between August 2008 and October 2009. Participants in our study were asked to compare their own chances of experiencing a range of risks and benefits related to the trial they were enrolled in with the chances of the other trial participants. We found a significant optimistic bias in their responses. Respondents tended to overestimate the benefits of the trial they were enrolled in and underestimate its risks. In addition, we found no significant relationship between respondents’ understanding of the trial’s purpose and how susceptible they were to unrealistic optimism. Our findings suggest that improving the consent process for oncology studies requires more than addressing deficits in understanding. (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)

If people sometimes participate in research because of altruism—because they want to help in the search for treatments—should we revise our views about what kinds of experiments are ethical? If participants act out of altruism, we might let them accept greater risks than we would if they are motivated only by a desire for personal gain. But how can we know when participants are genuinely altruistic?

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)

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)

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)

The movement in bioethics toward disclosure of financial conflicts of interest is well and good, most of the time. But in some cases, disclosure is not only unnecessary but destructive. When bioethicists advance arguments whose premises and logical moves are open to scrutiny, disclosure—far from clearing the air of bias—introduces bias.

: "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.

Competitor intelligence, information that helps managers understand their competitors, is highly valued in today's marketplace. Firms, large and small, are taking a more systematic approach to competitor intelligence collection. At the same time, information crimes and litigation over information disputes appear to be on the rise, and survey data show widespread approval of unethical and questionable intelligence-gathering methods. Despite these developments, few corporations address the ethics of intelligence gathering in their corporate codes of conduct. Neither managers nor management educators have (...) paid sufficient attention to this topic. From a review of questionable intelligence-gathering practices reported in various literatures, the author identifies some important ethical principles to help managers draw the line between legitimate and illegitimate methods of information acquisition. The paper also discusses the costs of failure to heed these principles and suggests steps managers can take to provide ethical leadership in this area. (shrink)

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)

“Recognizing that prisons disproportionately confine sick people, with mental illness, substance abuse, HIV disease among other illnesses; and that prisoners are subject to further morbidity and mortality in these institutions, due to lack of access and/or resources for health care, overcrowding, violence, emotional deprivation, and suicide.… condemns the social practice of mass imprisonment.”After decades of steady decline, tuberculosis has emerged as a significant public health threat in the United States. The rising rates of tuberculosis cases, an increasing proportion of which (...) are resistant to standard chemotherapies, are linked to the many scourges threatening our communities: the explosion of poverty, drug use, violence, the HIV epidemic, and the concomitant rise in congregate housing including homeless shelters, residential drug treatment programs and incarceration facilities. Jails and prisons have disproportionately high rates of tuberculosis infection and have been implicated as points of tuberculosis spread and, as such, are a critical point for tuberculosis control interventions. (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)

(2004). Inserting the ‘Race’ into Critical Pedagogy: An analysis of ‘race‐based epistemologies’. Educational Philosophy and Theory: Vol. 36, No. 2, pp. 153-165.

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)

In the United States there is an increasing tendency to view the only educational research worthy of federal funding as that which is designed as an experiment using randomised controls. One of the foundational assumptions underlying this research design is that the results of such research are meant to be generalisable beyond any particular research study. The purpose of this paper is to historicise the assumption of generalisability by explaining the ways in which it is a particularly modern research project. (...) By historicising generalisability, I show the ways in which the current research standards are products of culturally specific historical circumstances. In other words, generalisability is a local phenomenon and not generalisable to other times and places. (shrink)

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