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)

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)

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)

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)

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)

This special volume of Studies in Christian Ethics constitutes the most significant continuation to date of Christian social ethics in the tradition of Ronald Preston. It brings together leading scholars and new voices in the field from around the world, covering a broad range of contemporary issues, including globalisation, poverty, feminism, civil society, economics and religious pluralism.

This special volume of Studies in Christian Ethics constitutes the most significant continuation to date of Christian social ethics in the tradition of Ronald Preston. It brings together leading scholars and new voices in the field from around the world, covering a broad range of contemporary issues, including globalisation, poverty, feminism, civil society, economics and religious pluralism.

© 2015, Springer-Verlag Berlin Heidelberg.Genetic studies have identified single nucleotide polymorphisms associated with the risk of prostate cancer. It remains unclear whether such genetic variants are associated with disease aggressiveness. The NCI-SPORE Genetics Working Group retrospectively collected clinicopathologic information and genotype data for 36 SNPs which at the time had been validated to be associated with PC risk from 25,674 cases with PC. Cases were grouped according to race, Gleason score and aggressiveness. Statistical analyses were used to compare the frequency (...) of the SNPs between different disease cohorts. After adjusting for multiple testing, only PC-risk SNP rs2735839 was significantly and inversely associated with aggressive and high-grade disease in European men. Similar associations with aggressive and high-grade disease were documented in African-American subjects. The G allele of rs2735839 was associated with disease aggressiveness even at low PSA levels in both European and African-American men. Our results provide further support that a PC-risk SNP rs2735839 near the KLK3 gene on chromosome 19q13 may be associated with aggressive and high-grade PC. Future prospectively designed, case-case GWAS are needed to identify additional SNPs associated with PC aggressiveness. (shrink)

This special issue focuses on the question of how professionals who deal with complicated, boundary-crossing, global challenges can develop judgment skills for ethically using the discretion they h...

The intuition that consciousness is hard to explain may fade away as empirically adequate theories of consciousness develop. We review socio-historical factors that account for why, as a field, the neuroscience of consciousness has not been particularly successful at developing empirically adequate theories. Based on this we argue that the meta-problem may be a self-fulfilling prophecy, created in part because we inadvertently focused too much on the so-called 'hard problem', limiting scientific progress.

Ethics; philosophy; civilization, modern.