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

A community's abilities to promote health and maximize its response to public health threats require fulfillment of one of the four elements of public health legal preparedness, the capacity to effectively coordinate law-based efforts across different governmental jurisdictions, as well as across multiple sectors and disciplines. Government jurisdictions can be viewed “vertically” in that response efforts may entail coordination in the application of laws across multiple levels, including local, state, tribal, and federal governments, and even with international organizations. Coordination of (...) legal responses to public health emergencies also may involve a horizontal dimension comprising numerous and diverse sectors, such as public health, public and private health care, emergency management, education, law enforcement, the judiciary, and the military.Although responses to many acute health threats can implicate multiple jurisdictions and sectors, the jurisdictional and sectoral dimensions of legal preparedness are complex and may vary substantially by the nature of a threat, its geographic and geopolitical extent, and the operational response demanded. (shrink)

Psychiatry is rapidly adopting digital phenotyping and artificial intelligence/machine learning tools to study mental illness based on tracking participants’ locations, online activity, phone and text message usage, heart rate, sleep, physical activity, and more. Existing ethical frameworks for return of individual research results (IRRs) are inadequate to guide researchers for when, if, and how to return this unprecedented number of potentially sensitive results about each participant’s real-world behavior. To address this gap, we convened an interdisciplinary expert working group, supported by (...) a National Institute of Mental Health grant. Building on established guidelines and the emerging norm of returning results in participant-centered research, we present a novel framework specific to the ethical, legal, and social implications of returning IRRs in digital phenotyping research. Our framework offers researchers, clinicians, and Institutional Review Boards (IRBs) urgently needed guidance, and the principles developed here in the context of psychiatry will be readily adaptable to other therapeutic areas. (shrink)

Many epistemologists are enamored with a defeat condition on knowledge. In this paper we present some implementation problems for defeatism, understood along either internalist or externalist lines. We then propose that one who accepts a knowledge norm of belief, according to which one ought to believe only what one knows, can explain away much of the motivation for defeatism. This is an important result, because on the one hand it respects the plausibility of the intuitions about defeat shared by many (...) in epistemology; but on the other hand, it obviates the need to provide a unified account of defeat which plays well with the most plausible views of how knowledge fits with evidential probability. (shrink)

According to the Constitution View of persons, a human person is wholly constituted by (but not identical to) a human organism. This view does justice both to our similarities to other animals and to our uniqueness. As a proponent of the Constitution View, I defend the thesis that the coming-into-existence of a human person is not simply a matter of the coming-into-existence of an organism, even if that organism ultimately comes to constitute a person. Marshalling some support from developmental psychology, (...) I give a broadly materialistic account of the coming-into-existence of a human person. I argue for the metaphysical superiority of the Constitution View to Biological Animalism, Thomistic Animalism, and other forms of Substance Dualism. I conclude by discussing the single implication of the Constitution View for thinking about abortion. Footnotesa Thanks to Gareth Matthews and Catherine E. Rudder for comments. I am also grateful to other contributors to this volume, especially Robert A. Wilson, Marya Schechtman, David Oderberg, Stephen Braude, and John Finnis. (shrink)

What methodology should philosophers follow? Should they rely on methods that can be conducted from the armchair? Or should they leave the armchair and turn to the methods of the natural sciences, such as experiments in the laboratory? Or is this opposition itself a false one? Arguments about philosophical methodology are raging in the wake of a number of often conflicting currents, such as the growth of experimental philosophy, the resurgence of interest in metaphysical questions, and the use of formal (...) methods. This outstanding collection of specially-commissioned chapters by leading international philosophers discusses these questions and many more. It provides a comprehensive survey of philosophical methodology in the most important philosophical subjects: metaphysics, epistemology, philosophy of language, philosophy of mind, phenomenology, philosophy of science, ethics, and aesthetics. A key feature of the collection is that philosophers discuss and evaluate contrasting approaches in each subject, offering a superb overview of the variety of methodological approaches - both naturalistic and non-naturalistic - in each of these areas. They examine important topics at the heart of methodological argument, including the role of intuitions and conceptual analysis, thought experiments, introspection, and the place that results from the natural sciences should have in philosophical theorizing. The collection begins with a fascinating exchange about philosophical naturalism between Timothy Williamson and Alexander Rosenberg, and also includes contributions from the following philosophers: Lynne Rudder Baker, Matt Bedke, Greg Currie, Michael Devitt, Matthew C. Haug, Jenann Ismael, Hilary Kornblith, Neil Levy, E.J. Lowe, Kirk Ludwig, Marie McGinn, David Papineau, Matthew Ratcliffe, Georges Rey, Jeffrey W. Roland, Barry C. Smith, Amie L. Thomasson, Valerie Tiberius, Jessica Wilson, and David W. Smith. (shrink)

This article replies to Lynne Rudder Baker and Gareth B. Matthews’s “Anselm’s Argument Reconsidered,” in which the authors claim to have produced a sound version of Anselm’s ontological argument. Using Gaunilo’s “lost island” counterexample, this article explores the question whether an Anselmian argument can prove the existence of the greatest conceivable being without relying on premises that also prove the existence of the greatest conceivable island. A premise crucial to any such argument is a “greatness principle,” about which there (...) has recently been scholarly disagreement. This article examines two versions: (GP′) If it is in the understanding alone, it can be conceived to exist in reality also, which is greater, and (GP*) If it exists in the understanding alone, that which is greater can be conceived to exist in reality also. A distinctive feature of Baker and Matthews’s approach is that it countenances some “objects of thought” that not only do not exist in reality but logically cannot exist in reality. They then argue that for any conceivable island, a greater island is conceivable, but that there cannot be a conceivable being greater than the greatest conceivable being. Their strategy is vulnerable on two counts. It does not address the possibility that there is no upper limit to greatness in conceivable beings. Nor does it assure us that the greatest conceivable being is even logically possible. Thus their version of Anselm’s argument is inconclusive. (shrink)

The Wnt family of developmental regulators were named after the Drosophila segmentation gene wingless and the murine proto‐oncogene int‐1. Homology between these two genes connected oncogenesis to cell‐cell signals in development. I review how wingless was initially characterized, and cloned, as part of the quest to identify developmental cell‐to‐cell signals, based on predictions of the Positional Information Model, and on the properties of homeotic and segmentation gene mutants. The requirements and cell‐nonautonomy of wingless in patterning multiple embryonic and adult structures (...) solidified its status as a candidate signaling molecule. The physical location of wingless mutations and transcription unit defined the gene and its developmental transcription pattern. When the Drosophila homolog of int‐1 was then isolated, and predicted to encode a secreted proto‐oncogene homolog, it's identity to the wingless gene confirmed that a developmental cell‐cell signal had been identified and connected cancer to development. (shrink)

The contention that paternalism can be modernised in such a way as to avoid the usual criticisms is examined and dismissed. The alleged 'modernisation' consists simply in going through the motions of achieving the patient's free consent, while leaving the ultimate decision to the physician. Paternalism in this form is no better than the more old-fashioned variety, since it still takes away from patients the fundamental human right to make decisions about their own fate.

In the last decade of his life C.S. Peirce began to formulate a purely geometrical theory of continuity to supersede the collection-theoretic theory he began to elaborate around the middle of the 1890s. I argue that Peirce never succeeded in fully formulating the later theory, and that while that there are powerful motivations to adopt that theory within Peirce’s system, it has little to recommend it from an external perspective.

Mathematical naturalism forbids philosophical interventions in mathematical practice. This principle, strictly construed, places severe constraints on legitimate philosophizing about mathematics; it is also arguably incompatible with mathematical realism. One argument for the latter conclusion charges the realist with inability to take a truly naturalistic view of the Gödel Program in set theory. This argument founders on the disagreement among mathematicians about that program's prospects for success. It also turns out that when disagreements run this deep it is counterproductive to take (...) too narrow a view of how philosophers of mathematics may legitimately proceed. (shrink)

: In the Cambridge Conferences Lectures of 1898 Peirce defines a continuum as a "collection of so vast a multitude" that its elements "become welded into one another." He links the transinfinity (the "vast multitude") of a continuum to the confusion of its elements by a line of mathematical reasoning closely related to Cantor's Theorem. I trace the mathematical and philosophical roots of this conception of continuity, and examine its unresolved tensions, which arise mainly from difficulties in Peirce's theory of (...) collections. (shrink)

Abstract:Sustainable development and built heritage are oft-naturalized hegemonic discourses of the dominant social class. However, under the lens of critical sociomateriality, these categories destabilize—and in Brexit-era London, epicenter of a financial and technological capitalist circulatory space, “all that is solid melts” into the scopal regime of London's View Management Framework (LVMF). Analyzing multiple discourses of Southwark's Strata SE1— billed London's first “sustainable tower”—and adaptive reuse of the historically preserved Lambeth Water Tower, I argue that these structures constitute ‘interface objects’ in (...) a broader relational geography imbricating physical material, social objects, gentrification and the naturalized epistemologies of hegemonic development within London's skyline itself. I offer a reading of critical sociomateriality which illuminates rhythms of daily life within spatial-technological systems of energy provision, urban metabolic processes, as well as “hegemonic premiums,” what Richard Barras terms expected return on symbolic capital vis-à-vis the dominant panopticism of the LVMF. This paper contributes a theorization of critical sociomateriality, operating across a diversity of scales, tactics, and disciplines, analyzing discourses and practices which insinuate politics, artifacts, and technologies across contested issues. Critical sociomateriality is presented as a methodology for deconstructing tactics for inhabiting and interfacing with ‘sustainability’ through London's skyline in an unequal capitalist system marked by dissensus over runaway development, social precarity, and inequality in lived experiences of the urban environment. (shrink)

In 1887 Georg Cantor gave an influential but cryptic proof of theimpossibility of infinitesimals. I first give a reconstruction ofCantor's argument which relies mainly on traditional assumptions fromEuclidean geometry, together with elementary results of Cantor's ownset theory. I then apply the reconstructed argument to theinfinitesimals of Abraham Robinson's nonstandard analysis. Thisbrings out the importance for the argument of an assumption I call theChain Thesis. Doubts about the Chain Thesis are seen to render thereconstructed argument inconclusive as an attack on the (...) infinitelysmall. (shrink)

Sadness is generally seen as a negative emotion, a response to distressing and adverse situations. In an aesthetic context, however, sadness is often associated with some degree of pleasure, as suggested by the ubiquity and popularity, throughout history, of music, plays, films and paintings with a sad content. Here, we focus on the fact that music regarded as sad is often experienced as pleasurable. Compared to other art forms, music has an exceptional ability to evoke a wide-range of feelings and (...) is especially beguiling when it deals with grief and sorrow. Why is it, then, that while human survival depends on preventing painful experiences, mental pain often turns out to be explicitly sought through music? In this article we consider why and how sad music can become pleasurable. We offer a framework to account for how listening to sad music can lead to positive feelings, contending that this effect hinges on correcting an ongoing homeostatic imbalance. Sadness evoked by music is found pleasurable (1) when it is perceived as non-threatening; (2) when it is aesthetically pleasing; and (3) when it produces psychological benefits such as mood regulation, and empathic feelings, caused, for example, by recollection of and reflection on past events. We also review neuroimaging studies related to music and emotion and focus on those that deal with sadness. Further exploration of the neural mechanisms through which stimuli that usually produce sadness can induce a positive affective state could help the development of effective therapies for disorders such as depression, in which the ability to experience pleasure is attenuated. (shrink)

The philosophy of mathematics plays a vital role in the mature philosophy of Charles S. Peirce. Peirce received rigorous mathematical training from his father and his philosophy carries on in decidedly mathematical and symbolic veins. For Peirce, math was a philosophical tool and many of his most productive ideas rest firmly on the foundation of mathematical principles. This volume collects Peirce’s most important writings on the subject, many appearing in print for the first time. Peirce’s determination to understand matter, the (...) cosmos, and "the grand design" of the universe remain relevant for contemporary students of science, technology, and symbolic logic. (shrink)

Beginning in 2002, Wells Fargo began opening fraudulent accounts for unsuspecting customers. Stakeholders at every level either participated in, ignored, or tolerated the bank’s behavior that defrauded consumers on a massive scale. These unethical and well-documented schemes spanned more than a decade. Using public sources, this case recounts the events and ethical lapses that unfolded over the multiyear investigation of the Wells Fargo fraudulent accounts scandal and illuminates the general systemic failures of corporate culture and governance, public regulation, and market (...) responses to promote ethical business practices. This case provides the opportunity to consider what means for fostering ethical conduct might exist if a corporation can be big enough and rich enough that civil, criminal, regulatory, and market forces cannot deter unethical corporate practices, and if the market does not punish the corporation for a culture that promotes fraud. (shrink)

Background To describe the preferences for disclosure of individual biomarker results among mothers participating in a longitudinal birth cohort. Methods We surveyed 343 mothers that participated in the Health Outcomes and Measures of the Environment Study about their biomarker disclosure preferences. Participants were told that the study was measuring pesticide metabolites in their biological specimens, and that the health effects of these low levels of exposure are unknown. Participants were asked whether they wanted to receive their results and their child's (...) results. In addition, they were asked about their preferred method (letter vs in person) and format (more complex vs less complex) for disclosure of results. Results Almost all of the study participants wanted to receive their individual results (340/343) as well as their child's results (342/343). However, preferences for receiving results differed by education level. Mothers with less than a college degree preferred in-person disclosure of results more often than mothers with some college education or a college degree (34.3% vs 17.4% vs 7.9%, p<0.001). Similarly, mothers with less than a college education preferred a less complex disclosure format than mothers with some college education or a college degree (59.7% vs 79.1% vs 86.3%, p<0.0001). Conclusion While almost all study participants preferred to receive results of their individual biomarker tests, level of education was a key factor in predicting preferences for disclosure of biomarker results. To ensure effective communication of this information, disclosure of biomarker results should be tailored to the education level of the study participants. (shrink)

Nonsense‐mediated RNA decay (NMD) represents an established quality control checkpoint for gene expression that protects cells from consequences of gene mutations and errors during RNA biogenesis that lead to premature termination during translation. Characterization of NMD‐sensitive transcriptomes has revealed, however, that NMD targets not only aberrant transcripts but also a broad array of mRNA isoforms expressed from many endogenous genes. NMD is thus emerging as a master regulator that drives both fine and coarse adjustments in steady‐state RNA levels in the (...) cell. Importantly, while NMD activity is subject to autoregulation as a means to maintain homeostasis, modulation of the pathway by external cues provides a means to reprogram gene expression and drive important biological processes. Finally, the unanticipated observation that transcripts predicted to lack protein‐coding capacity are also sensitive to this translation‐dependent surveillance mechanism implicates NMD in regulating RNA function in new and diverse ways. (shrink)

Can a scientific naturalist be a mathematical realist? I review some arguments, derived largely from the writings of Penelope Maddy, for a negative answer. The rejoinder from the realist side is that the irrealist cannot explain, as well as the realist can, why a naturalist should grant the mathematician the degree of methodological autonomy that the irrealist's own arguments require. Thus a naturalist, as such, has at least as much reason to embrace mathematical realism as to embrace irrealism.

My dissertation explores the foundations of ethics—the question of whether and where practical justification comes to an end. What reason do we have to be moral? Is the fact that something is pleasurable at least a defeasible reason to pursue it, and if so, why? I argue that the only way to answer such questions is to look at what is constitutive of action. Nonnormative facts about the nature of agency can ground the normative authority of reasons for action. Recently, (...) an influential group of externalists about reasons for action have argued that normativity is sui generis and cannot be further explained. Recently, too, many of the most prominent internalists to offer an explanation of normative force have merely assimilated the problem to one about motivational force. I argue that neither position is satisfactory. We need answers to our practical questions, and externalism has none to offer beyond brute intuitions. A purely motivational internalism, on the other hand, seems to fall well short of a normative theory. Appeals to facts about motivation do not answer the question of what we have reason to do; they bypass it in favor of the question of what we are going to do. Fortunately, there is a middle way that combines the best of both views: constitutivism. An account of practical normativity based on action’s constitutive aim can explain both how we are governed or moved by reasons and how those reasons have genuine, objective authority. The constitutive aim of action sets the agenda for practical reasoning, and considerations that engage this aim are the ones that bring such reasoning to a close. They settle the practical question of what to do. But if, as I maintain, the normative question of what I ought to do (or what I have reason to do) seeks considerations that bear on the practical question of what to do, then answers to the latter are ipso facto answers to the former. In this way, nonnormative facts about what closes practical deliberation can ground fully normative facts about what we have reason to do. (shrink)

The Archimedean Axiom is often held to be an intuitively obvious truth about the geometry of physical space. After a general discussion of the varieties of geometrical intuition that have been proposed, I single out one variety which we can plausibly be held to have and then argue that it does not underwrite the intuitive obviousness of the Archimedean Axiom. Generalizing that result, I conclude that the Axiom is not intuitively obvious.

The proposed heavy dependence on Pavlovian conditioning to account for social behavior confounds phylogenically and ontogenically selected behavior patterns and ignores the extension of the principle of selection by consequences from biological to learning theory. Instead of acknowledging operant relations, Domjan et al. construct vaguely specified mechanisms based upon anticipatory cost-benefit considerations that are not supported by the Pavlovian conditioning literature.

From his earliest published writings to his last, Roman Ingarden displayed an interest in theoretical biology and its efforts to clarify what distinguishes living organisms from other types of entities. However, many of his explorations of such issues are easily overlooked, because they don’t appear in works that are primarily ontological, metaphysical, or anthropological in nature but are “hidden” within his works on literary aesthetics, where Ingarden sought to define the nature of living organisms in order to compare literary works (...) to such entities. This article undertakes a historical textual analysis that traces the evolution of Ingarden’s thought regarding the nature of the literary work of art as an organism-like entity and uncovers its links with the simultaneous development of his systems theory and its central concept of the “relatively isolated system”: for Ingarden, a literary work and an organism are each a systematically transforming, “living,” functional-structural whole that comprises a system of hierarchically arranged and partially isolated elements whose harmonious interaction allows the literary work or organism to fulfill its chief function. Having completed that historical analysis, we test Ingarden’s assessment of works of art as organism-like entities in a novel context by investigating the organism-like qualities of the contemporary computer game; insofar as their AI-driven behavior displays a form of agency, such games might appear to be even more “alive” than traditional works of art. We show that Ingarden’s conceptual framework provides a useful tool for understanding the “organicity” of such games as works of art, despite the fact that they differ qualitatively from those art forms with which Ingarden was directly familiar. (shrink)

To corroborate the music and social bonding hypothesis, we propose that future investigations isolate specific components of social bonding and consider the influence of context. We deconstruct and operationalize social bonding through the lens of social psychology and provide examples of specific measures that can be used to assess how the link between music and sociality varies by context.

To clarify Vattimo’s position on secularism and Islam, I first discuss his view that secularisation as kenosis and caritas entails the nihilistic vocation of Being, as expressed in our postmodern world where there appear to be no facts, only interpretations. I then survey some of Vattimo’s negative judgements of Islam, which appear to be out of keeping with his own disavowal of “modern” ideals such as “progress” and “grand narratives.” After analysing Islam’s turbulent history of secularism, I suggest the need (...) for Islamic secularism for its own religious and political reasons. Vattimo’s theory of secularisation helps to identify not only what Islam should avoid in pursuing its own secularisation, but also what it can emphasise within its own tradition as a stimulus towards secularisation: the Golden Rule. This rule, if presented by influential imams as spiritually and as ethically open to the other as possible, may lead through action-based dialogue to a form of reciprocal listening that is the core of Vattimo’s notion of secularism, but which is based, at the same time, on the awareness of the gulf between the transcendence of Allah and the finitude and fallibility of human politico-religious institutions. (shrink)

A personal leadership fable on applying principles of Zen to work and life choices The Shibumi Strategy is a little book about a big breakthrough. It tells the story of a hardworking family man who finds himself in crisis when his company closes. Through his struggle, and guidance from unlikely sources, he learns subtle lessons in the form of "personal zen" principles, coming to understand that it is often the involuntary challenge, the setbacks, that harbor the power to transform. When (...) approached as an opportunity - no easy task-unforeseen trials can sometimes result in an altogether new lease on life. Shows how "personal leadership" can lead to real (and not always easy) breakthroughs Includes key lessons on commitment, preparation, struggle, breakthrough, and transformation Is based on Shibumi, a Japanese word without literal definition the describes the height of personal excellence, elegant performance, and effortless effectiveness For those struggling with personal breakthroughs, The Shubimi Strategy offers a new way to face work and life challenges for balanced solutions. (shrink)

Research has suggested that nostalgia is a mixed, albeit predominantly positive emotion. One proposed function of nostalgia is to attenuate the negative consequences of loneliness. This restorative effect of nostalgia, however, has been demonstrated with cross sectional and experimental methods that lack ecological validity. In studies that have measured nostalgia in daily life, however, nostalgia has been negatively related to well-being. We propose an alternative theory that posits that the effect of nostalgia on well-being depends on the event or experience (...) that elicits nostalgia. We tested this theory by measuring daily states of nostalgia, loneliness, and affect across five daily diary studies (N = 504; 6,004 daily reports) that lasted for 14 days. Using multilevel modeling, we found that nostalgia and loneliness were negatively related to positive affect and positively related to negative affect. The negative effects of nostalgia on affective well-being were significantly stronger on days when people felt more lonely as opposed to less lonely. Viewed alternatively, the negative effects of loneliness on affective well-being were stronger on days when people felt more vs. less nostalgic. Thus, in contrast to experimental findings, nostalgia did not attenuate, but rather exaggerated the negative effects of loneliness on affective well-being. These findings support a theoretical account that proposes that the effect of nostalgia on well-being depends on the natural context in which nostalgia is elicited. (shrink)

This book presents strategies for using systemic theory and evidence-based practice in schools to support students, the adults in their lives, and their wider communities. Beginning by introducing and explaining the Advocating Students-within-Environments (ASE) theory, each chapter then addresses a specific school-based issue, such as academic achievement, crisis, trauma, and resiliency, from a systemic and environmental lens. Practical and accessible, the chapters are filled with case examples, evidence-base interventions, and helpful tools to show how counselors can incorporate the approach into (...) their practice. Extending beyond school and student problems, this text also explores greater system functioning, such as community outreach and state level intervention, discussing advocacy and political issues. This book is essential for school-based professionals who are looking for new ways to work with students, families, and their communities. It will also be of interest to mental health professionals who work systemically, such as marriage and family therapists and community counselors. (shrink)