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)

In the Platonic work Alcibiades I, a divinely guided Socrates adopts the guise of a lover in order to divert Alcibiades from an unthinking political career. The contributors to this carefully focussed volume cover aspects of the background to the work; its arguments and the philosophical issues it raises; its relationship to other Platonic texts, and its subsequent history up to the time of the Neoplatonists. Despite its ancient prominence, the authorship of Alcibiades I is still unsettled; the essays and (...) two appendices, one historical and one stylometric, come together to suggest answers to this tantalising question. (shrink)

What are the processes, from conception to adulthood, that enable a single cell to grow into a sentient adult? The processes that occur along the way are so complex that any attempt to understand development necessitates a multi-disciplinary approach, integrating data from cognitive studies, computational work, and neuroimaging - an approach till now seldom taken in the study of child development. Neuroconstructivism is a major new 2 volume publication that seeks to redress this balance, presenting an integrative new framework for (...) considering development. In the first volume, the authors review up-to-to date findings from neurobiology, brain imaging, child development, computer and robotic modelling to consider why children's thinking develops the way it does. They propose a new synthesis of development that is based on 5 key principles found to operate at many levels of descriptions. They use these principles to explain what causes a number of key developmental phenomena, including infants' interacting with objects, early social cognitive interactions, and the causes of dyslexia. The "neuroconstructivist" framework also shows how developmental disorders do not arise from selective damage to normal cognitive systems, but instead arise from developmental processes that operate under atypical constraints. How these principles work is illustrated in several case studies ranging from perceptual to social and reading development. Finally, the authors use neuroimaging, behavioural analyses, computational simulations and robotic models to provide a way of understanding the mechanisms and processes that cause development to occur. Computer and robotic models provide concrete tools for investigating the processes and mechanisms involved in learning and development. Volume 2 illustrates the principles of 'Neuroconstructivist' development, with contributions from 9 different labs across the world. Each of the contributions illustrates how models play a central role in understanding development. The models presented include standard connectionist neural network models as well as multi-agent models. Also included are robotic models emphasizing the need to take embodiment and brain-system interactions seriously. A model of Autism and one of Specific Language Impairment also illustrate how atypical development can be understood in terms of the typical processes of development but operating under restricted conditions. This volume complements Volume 1 by providing concrete examples of how the 'Neuroconstructivist' principles can be grounded within a diverse range of domains, thereby shaping the research agenda in those domains. (shrink)

Is 50 considered “old”? When do we stop being considered “young”? If individuals could choose to be any age, what would it be? In a sample of 502,548 internet respondents ranging in age from 10 to 89, we examined age differences in aging perceptions (e.g., how old do you feel?) and estimates of the timing of developmental transitions (e.g., when does someone become an older adult?). We found that older adults reported older perceptions of aging (e.g., choosing to be older, (...) feeling older, being perceived as older), but that these perceptions were increasingly younger than their current age. The age to which individuals hope to live dramatically increased after age 40. We also found that older adults placed the age at which developmental transitions occurred later in the life course. This latter effect was stronger for transitions involving middle-age and older adulthood compared to transitions involving young adulthood. The current study constitutes the largest study to date of age differences in age perceptions and developmental timing estimates and yielded novel insights into how the aging process may affect judgments about the self and others. (shrink)

Endothelial cells line the inside of all blood vessels, forming a structurally and functionally heterogenous population of cells. Their complexity and diversity has long been recognized, yet very little is known about the molecules and regulatory mechanisms that mediate the heterogeneity of different endothelial cell populations. The constitutive organ‐ and microenvironment‐specific phenotype of endothelial cells controls internal body compartmentation, regulating the trafficking of circulating cells to distinct vascular beds. In contrast, surface molecules associated with the activated cytokine‐inducible endothelial phenotype play (...) a critical role in pathological conditions including inflammation, tumor angiogenesis, and wound healing. Differentiation of the endothelial cell phenotypes appears to follow similar mechanisms to the differentiation of hematopoietic cells, with the exception that endothelial cells maintain transdifferentiating competence. The present review offers a scheme of endothelial cell differentially expressed endothelial cell molecules as targets for directed therapeutic intervention. (shrink)

Drawing on 171 in-depth interviews with physicists at universities in the United States and the UK, this study examines the narratives of 48 physicists to explain the concept of ethical ambiguity: the border where legitimate and illegitimate conduct is blurred. Researchers generally assume that scientists agree on what constitutes both egregious and more routine forms of misconduct in science. The results of this study show that scientists perceive many scenarios as ethically gray, rather than black and white. Three orientations to (...) ethical ambiguity are considered—altruism, inconsequential outcomes, and preserving the status quo—that allow possibly questionable behavior to persist unchallenged. Each discursive strategy is rationalized as promoting the collective interest of science rather than addressing what is ethically correct or incorrect. The results of this study suggest that ethics training in science should focus not only on fabrication, falsification, and plagiarism and more routine forms of misconduct, but also on strategies for resolving ethically ambiguous scenarios where appropriate action may not be clear. (shrink)

Late in 1990, the Center for the Study of Ethics in the Professions at Illinois Institute of Technology (lIT) received a grant of more than $200,000 from the National Science Foundation to try a campus-wide approach to integrating professional ethics into its technical curriculum.! Enough has now been accomplished to draw some tentative conclusions. I am the grant's principal investigator. In this paper, I shall describe what we at lIT did, what we learned, and what others, especially philosophers, can learn (...) from us. We set out to develop an approach that others could profitably adopt. I believe that we succeeded. (shrink)

When there are disasters in our society, whether on an individual, organizational or systemic level, individuals or groups of individuals are often singled out for blame, and commonly it is assumed that the alleged culprits engaged in deliberate misdeeds. But sometimes, at least, these disasters occur not because of deliberate malfeasance, but rather because of complex organizational and systemic circumstances that result in these negative outcomes. Using the Boeing Corporation and its 737 MAX aircraft crashes as an example, this ethical (...) analysis will examine some of the organizational problems that led to changes in management in Boeing and ultimately resulted in the fatal accidents. We will examine ethical blind spots within the company that led to the deadly accidents, and we will study the kinds of circumstances that are particularly acute in organizations such as Boeing, and which contributed to the malfunctions in the 737 MAX and the two resulting crashes. The Boeing 737 MAX example is not a singular case, but rather shares similarities with other engineering disasters such as the Challenger and Columbia explosions, and the ignition switch failures at General Motors each of which seem to have been at least partly the result of organizational shortcomings involving a compromise in commitment to safety. These parallels lead us to conclude that organizational malfeasance poses a serious ethical challenge for engineers and their organizations. We will conclude with some tentative suggestions for avoiding such tragic incidents in the future. (shrink)

Entrepreneurs of contested commodities often face stakeholders engaged in market excluding boundary work driven by ethical considerations. For example, the conversion of academic scientific knowledge into technologies that can be owned and sold is a growing global trend and key stakeholders have different ethical responses to this contested commodity. Commercialization of science can be viewed as a good thing because people believe it bolsters economic growth and broadly benefits society. Others view it as bad because they believe it discourages basic (...) research that ought to be freely shared without concern for profit. Taking a descriptive sociological approach, we posit that the stance of a religious tradition toward capitalism will help shape individual scientists’ views on science commercialization and test whether the religious tradition of scientists correlates with their attitude toward the commercialization of science. To maximize variance on the religious tradition dimension, we analyze pooled data from a cross-national survey of university biologists and physicists encompassing France, Hong Kong, India, Italy, Taiwan, Turkey, UK and the USA. We indeed find religious tradition differences. Hindus and scientists with no religious tradition are more likely to agree that commercialization of science “harms a university’s commitment to knowledge production” than Protestants. We end with a discussion on business ethics and the moral limits of the market as well as implications for entrepreneurs of contested commodities. (shrink)

He further argues that it is necessary to rethink traditional conceptions of argument, and to find a position that avoids the limitations of both the highly abstract approach of formal logic and the highly contextualized approaches of rhetoric and communication theory.".

Is the market civilizing or destructive? The increased salience of science commercialization is forcing scientists to address this question. Benefiting from the sociology of morality literature’s increased attention to specific kinds of morality and engaging with economic sociology’s moral markets literature, we generate competing hypotheses about scientists’ value-driven attitudes toward patenting. The Civilizing Market thesis suggests scientists who prioritize universalism will tend to support patenting. The Destructive Market thesis, by contrast, suggests universalism will be correlated with opposition to patenting. We (...) analyze survey data from biologists and physicists nested within academic organizations, which are nested within the following regions: France, Hong Kong, India, Italy, Taiwan, Turkey, UK, and the USA. Employing multilevel analysis, we find correlational evidence to support the Destructive Market thesis. Universalism is associated with anti-patenting attitudes, suggesting scientists expect patenting to have deleterious effects on science and society. We end with a discussion of this article’s implications for the moral markets literature, sociology of morality and business ethics. (shrink)

There is little to indicate from, her circumstances that events would propel Helga Wanglie, an 86-year-old Minneapolis woman, into the center of public controversy. We know little of her life prior to the events that removed her from the world of conscious, sentient beings. By the time of her death on 4 July 1991, Mrs. Wanglie had become the focus of a nationwide public and professional debate on the rights of a patient in a persistent vegetative state to receive aggressive (...) medical treatment when such treatment is felt by the patient's doctors not to be in the patient's best interests. (shrink)

BackgroundReflexive pitch perturbation experiments are commonly used to investigate the neural mechanisms underlying vocal motor control. In these experiments, the fundamental frequency–the acoustic correlate of pitch–of a speech signal is shifted unexpectedly and played back to the speaker via headphones in near real-time. In response to the shift, speakers increase or decrease their fundamental frequency in the direction opposing the shift so that their perceived pitch is closer to what they intended. The goal of the current work is to develop (...) a quantitative model of responses to reflexive perturbations that can be interpreted in terms of the physiological mechanisms underlying the response and that captures both group-mean data and individual subject responses.MethodsA model framework was established that allowed the specification of several models based on Proportional-Integral-Derivative and State-Space/Directions Into Velocities of Articulators (DIVA) model classes. The performance of 19 models was compared in fitting experimental data from two published studies. The models were evaluated in terms of their ability to capture both population-level responses and individual differences in sensorimotor control processes.ResultsA three-parameter DIVA model performed best when fitting group-mean data from both studies; this model is equivalent to a single-rate state-space model and a first-order low pass filter model. The same model also provided stable estimates of parameters across samples from individual subject data and performed among the best models to differentiate between subjects. The three parameters correspond to gains in the auditory feedback controller’s response to a perceived error, the delay of this response, and the gain of the somatosensory feedback controller’s “resistance” to this correction. Excellent fits were also obtained from a four-parameter model with an additional auditory velocity error term; this model was better able to capture multi-component reflexive responses seen in some individual subjects.ConclusionOur results demonstrate the stereotyped nature of an individual’s responses to pitch perturbations. Further, we identified a model that captures population responses to pitch perturbations and characterizes individual differences in a stable manner with parameters that relate to underlying motor control capabilities. Future work will evaluate the model in characterizing responses from individuals with communication disorders. (shrink)

Assisted suicide is a tragic issue, one of those for which the tools of mere logic are inadequate and in which the power of the individual case is compelling and seductive but not necessarily clarifying. Meaningful dialogue is difficult. Persuasion is limited because the resolution of the issue, on a moral level, must be founded upon fundamental notions of what it means to be human, especially in the midst of suffering or disability or at the point of death.

There are important synergies for the next generation of ethical leaders based on the alignment of modified or adjusted mental models. This entails a synergistic application of moral imagination through collaborative input and critique, rather than "me too" obedience. In this article, we will analyze the Milgram results using frameworks relating to mental models (Werhane et al., Profitable partnerships for poverty alleviation, 2009), as well as work by Moberg on "ethics blind spots'' (Organizational Studies 27(3): 413-428, 2006), and by Bazerman (...) and Chugh on "bounded awareness" (Harvard Business Review, 2006; Mind & Society 6: 1-18, 2007) Using these constructs to examine the Milgram experiment, we will argue that the ways in which the experiments are framed, the presence of an authority figure, the appeal to the authority of science, and the situation in which the naïve participant finds herself or himself, all create a bounded awareness, a narrow blind spot that encourages a climate for obedience, brackets out the opportunity to ask the moral question: "Am I hurting another fellow human being?" and may preclude the subject from utilizing moral imagination to opt out of the experiment. We will conclude that these forms of almost blind obedience to authority are correctable, but with difficulty. We will argue that linking the modification of mental models to an unbinding of awareness represents an important synergistic relationship and one that can build effectively on the lessons learned from our experience with moral imagination. (shrink)

As scientific and engineering efforts become increasingly global in nature, the need to understand differences in perceptions of research ethics issues across countries and cultures is imperative. However, investigations into the connection between nationality and ethical decision-making in the sciences have largely generated mixed results. In Study 1 of this paper, a measure of biases and compensatory strategies that could influence ethical decisions was administered. Results from this study indicated that graduate students from the United States and international graduate students (...) studying in the US are prone to different biases. Based on these findings, recommendations are made for developing ethics education interventions to target these decision-making biases. In Study 2, we employed an ethics training intervention based on ethical sensemaking and used a well-established measure of ethical decision-making that more fully captures the content of ethical judgment. Similar to Study 1, the results obtained in this study suggest differences do exist between graduate students from the US and international graduate students in ethical decision-making prior to taking the research ethics training. However, similar effects were observed for both groups following the completion of the ethics training intervention. (shrink)

Several research groups have identified a network of regions of the adult cortex that are activated during social perception and cognition tasks. In this paper we focus on the development of components of this social brain network during early childhood and test aspects of a particular viewpoint on human functional brain development: “interactive specialization.” Specifically, we apply new data analysis techniques to a previously published data set of event-related potential ~ERP! studies involving 3-, 4-, and 12-month-old infants viewing faces of (...) different orientation and direction of eye gaze. Using source separation and localization methods, several likely generators of scalp recorded ERP are identified, and we describe how they are modulated by stimulus characteristics. We then review the results of a series of experiments concerned with perceiving and acting on eye gaze, before reporting on a new experiment involving young children with autism. Finally, we discuss predictions based on the atypical emergence of the social brain network. (shrink)