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)

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)

We investigated people's ability to infer others’ mental states from their emotional reactions, manipulating whether agents wanted, expected, and caused an outcome. Participants recovered agents’ desires throughout. When the agent observed, but did not cause the outcome, participants’ ability to recover the agent's beliefs depended on the evidence they got. When the agent caused the event, participants’ judgments also depended on the probability of the action ; when actions were improbable given the mental states, people failed to recover the agent's (...) beliefs even when they saw her react to both the anticipated and actual outcomes. A Bayesian model captured human performance throughout, consistent with the proposal that people rationally integrate information about others’ actions and emotional reactions to infer their unobservable mental states. (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)

Patient safety has only recently been subjected to wide-spread systematic study. Healthcare differs from other high risk industries in being more diverse and multi-contextual, and less certain and regulated. Also many patient safety problems are low-frequency events associated with many, varied contributing factors. The subject of this paper is the epistemology of patient safety (the science of the method of finding out about patient safety). Patient safety research is considered here on the background of a risk management framework which requires (...) researchers to: • Understand the context - as a subset of healthcare quality, services and systems research, with technical and human behavioural (cultural) components and a range of external and internal organisational influences, a wide range of research disciplines is necessary • Identify the risks - identify the things that go wrong and the frequency and nature of different types of incidents from sources such as medical record review, observational studies, audit, incident and medico-legal reports • Analyse the risks - deconstruct the things that go wrong, identifying contributing factors and trying to detect trends and patterns in contributing factors, detection, mitigation factors, ameliorating factors and actions taken to reduce risk • Evaluate the risks - decide on priorities, identifying preventive and corrective strategies and judging the risk- and cost-benefit of potential corrective strategies such as standardisation or simplification of a process or device • Manage the risk - evaluate and scope preventive and/or corrective strategies and then implement these, or place the problem on a risk register pending solution, or accept that what is needed is unaffordable • Communicate and consult - use interactive sessions, audit, on-going feedback, reminders and patient mediated prompts • Monitor and review the state of the problem - get baseline trends and patterns so that changes can be tracked and properly attributed to an intervention A hierarchy of levels of evidence has been proposed for clinical research and we argue that insufficient weighting has been given to lower ranked levels of research and to qualitative research, although critical interpretive synthesis is now gaining acceptance in mainstream thinking (e.g. by the Cochrane Collaboration). Fundamental challenges remain including how to grasp the elusive concept of patient safety, how to quantify, characterise and cost the problems, how to judge the extent to which harm can be attributed to errors, violations or system failures, how to identify contributing factors and the extent to which they can be implicated, how to judge whether incidents or their precursors are preventable, how to generate strong evidence to make healthcare safer and how to translate research into practice. Future directions include addressing the mundane as well as rare, dramatic events, and developing further research in non-hospital settings and in developing countries. In summary, a mixture of qualitative and quantitative methods, using information from all available data sources and combining retrospective, real time and prospective study designs, is necessary to address some of the more difficult patient safety problems. (shrink)

The American Medical Association enacted its Code of Ethics in 1847, the first such national codification. In this volume, a distinguished group of experts from the fields of medicine, bioethics, and history of medicine reflect on the development of medical ethics in the United States, using historical analyses as a springboard for discussions of the problems of the present, including what the editors call "a sense of moral crisis precipitated by the shift from a system of fee-for-service medicine to a (...) system of fee-for-system medicine, better known as 'managed care.'" The authors begin with a look at how the medical profession began to consider ethical issues in the 1800s and subsequent developments in the 1900s. They then address the sociological, historical, ethical, and legal aspects of the practice of medicine. Later chapters discuss current and future challenges to medical ethics and professional values. Appendixes display various versions of the AMA's Code of Ethics as it has evolved over time. Contributors: George J. Annas, J.D., M.P.H., Arthur Isak Applbaum, Ph.D., Robert B. Baker, Ph.D., Chester R. Burns, M.D., Ph.D., Arthur L. Caplan, Ph.D., Alexander Morgan Capron, J.D., Christine K. Cassel, M.D., Linda L. Emanuel, M.D., Ph.D., Eliot L. Freidson, Ph.D., Albert R. Jonsen, Ph.D., Stephen R. Latham, J.D., Ph.D., Susan E. Lederer, Ph.D., Florencia Luna, Ph.D., Edmund D. Pellegrino, M.D., Charles E. Rosenberg, Ph.D., Mark Siegler, M.D., Rosemary A. Stevens, Ph.D., Robert M. Tenery, Jr., M.D., Robert M. Veatch, Ph.D., John Harley Warner, Ph.D., Paul Root Wolpe, Ph.D. (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)

Memory, funerals, and the communion of the saints: growing old and practices of remembering / M. Therese Lysaught -- God bends over backward to accommodate humankind...while the Civil Rights Acts and the Americans with Disabilities Act require [only] minimum effort / Mary Jo Iozzio -- Radical solidarity: migration as challenge ofr contemporary Christian ethics / Kristin E. Heyer -- Catholic lesbian feminist theology / Mary E. Hunt -- Theology of whose body? Sexual conplementarity, intersex conditions, and La Virgen de Guadalupe (...) / Katie M. Grimes -- Social conscience and politics in the United States of America: reflections / Mary Jo Bane -- Pope Francis, women, and the church for the poor / Lisa A. Fullam -- Floodwaters and the ticking clock: the systematic oppression and stigmatization of poor, single mothers in American and Christian theological responses / Julie A. Mavity Maddalena --What causes inequity? / Dean Baker -- Engaging the U.S. Bishops' pastoral on crime and criminal justice: from atomism to community justice / Robert DeFina and Lance Hannon -- Reconstructing the moral claim of racially unjust mass incarceration / Alison Benders -- The systemic erasure of the Black/dark-skinned body in Catholic ethics / Bryan Massingale -- Anti-blackness and white supremacy in the making of American Catholicism / M. Shawn Copeland -- White privilege / Charles E. Curran -- The Black Lives Matter Movement: justice and health equity / Michael P. Jaycox -- Mujerista theology: a challenge to traditional theology / Ada María Isasi-Díaz -- Faith of our mothers; Catholic womanist God-talk / Diana L. Hayes. (shrink)

The article explores the private nature of subjectivity in programs of integration the phenomenology with naturalism. It is considered if their tools are relevant for the phenomenological, rather than naturalistic way of subjectivity’s explaining. Justification of the key ideas is provided with the help of such concepts as “body image”, “body scheme”, (Sh. Gallagher), “ontological significance” (L. Baker), “experience”, “cognitive niches” (F. Varela), “transparent body” (T. Fuchs). Based on the traditional phenomenology of E. Husserl, it is shown that a (...) set of approaches that integrate phenomenology and naturalism within the framework of “first-person philosophy” can be characterized as a phenomenology without a phenomenological subject. It is shown that the phenomenological nature of the self-perspective in integrative programs is more likely to be understood as the qualification and privacy of subjectivity, while the transcendental aspect of the unobservable and biased consciousness is practically not taken into account. The article concludes that the logic of some projects of integration of phenomenology and naturalism overlook this transcendental peculiarity of consciousness, its fundamentally unobserved character. The classical phenomenological approach emphasizes on the extra-natural, biased, and non-empirical nature of consciousness. The role and significance of the phenomenological approach is not limited to the idea of “what-is-likeness” and privacy of subjective states. Phenomenology, which preserves the idea of the subject, means a radical break with the ontology of things and, in general, with the ontology of something objective at all. (shrink)

Review of: Greek for Life: Strategies for Learning, Retaining, and Reviving New Testament Greek, by Benjamin L. Merkle, Robert L. Plummer, Grand Rapids, MI: Baker Academic, 2017, pp. 176, US$21.99.

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)

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)

The current article aims to provide an up-to-date synopsis of available techniques to study affect dynamics using intensive longitudinal data. We do so by introducing the following eight dichotomies that help elucidate what kind of data one has, what process aspects are of interest, and what research questions are being considered: single- versus multiple-person data; univariate versus multivariate models; stationary versus nonstationary models; linear versus nonlinear models; discrete time versus continuous time models; discrete versus continuous variables; time versus frequency domain; (...) and modeling the process versus computing descriptives. In addition, we discuss what we believe to be the most urging future challenges regarding the modeling of affect dynamics. (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)

Abstract. We argue that all human beings have a special type of dignity which is the basis for (1) the obligation all of us have not to kill them, (2) the obligation to take their well-being into account when we act, and (3) even the obligation to treat them as we would have them treat us, and indeed, that all human beings are equal in fundamental dignity. We give reasons to oppose the position that only some human beings, because of (...) their possession of certain characteristics in addition to their humanity (for example, an immediately exercisable capacity for self-consciousness, or for rational deliberation), have full moral worth. What distinguishes human beings from other animals, what makes human beings persons rather than things, is their rational nature, and human beings are rational creatures by virtue of possessing natural capacities for conceptual thought, deliberation, and free choice, that is, the natural capacity to shape their own lives. (shrink)

Neural substrates of fatigue in traumatic brain injury are not well understood despite the considerable burden of fatigue on return to productivity. Fatigue is associated with diminishing performance under conditions of high cognitive demand, sense of effort, or need for motivation, all of which are associated with cognitive control brain network integrity. We hypothesize that the pathophysiology of TBI results in damage to diffuse cognitive control networks, disrupting coordination of moment-to-moment monitoring, prediction, and regulation of behavior. We investigate the cingulo-opercular (...) and frontoparietal networks, which are engaged to sustain attention for task and maintain performance. A total of 61 individuals with mild TBI and 42 orthopedic control subjects participated in functional MRI during performance of a constant effort task requiring altering the amount of effort utilized to manually squeeze a pneumostatic bulb across six 30-s trials. Network-based statistics assessed within-network organization and fluctuation with task manipulations by group. Results demonstrate small group differences in network organization, but considerable group differences in the evolution of task-related modulation of connectivity. The mild TBI group demonstrated elevated CO connectivity throughout the task with little variation in effort level or time on task, while CO connectivity diminished over time in controls. Several interregional CO connections were predictive of fatigue in the TBI group. In contrast, FP connectivity fluctuated with task manipulations and predicted fatigue in the controls, but connectivity fluctuations were delayed in the mild traumatic brain injury group and did not relate to fatigue. Thus, the mTBI group’s hyper-connectivity of the CO irrespective of task demands, along with hypo-connectivity and delayed peak connectivity of the FP, may allow for attainment of task goals, but also contributes to fatigue. Findings are discussed in relation to performance monitoring of prediction error that relies on internal cues from sensorimotor feedback during task performance. Delay or inability to detect and respond to prediction errors in TBI, particularly evident in bilateral insula-temporal CO connectivity, corresponds to day-to-day fatigue and fatigue during task performance. (shrink)

The projection postulate, which prescribes “collapse of the state vector” upon measurement, is not an essential part of quantum mechanics. Rather it is only an optional discarding of certain branches of the state vector that are expected to be irrelevant for the purpose at hand. However, its use is hazardous, and there are examples of repeated measurements for which the conventional application of the projection postulate leads to incorrect results.

We study the embedding property in the category of sorted profinite groups. We introduce a notion of the sorted embedding property (SEP), analogous to the embedding property for profinite groups. We show that any sorted profinite group has a universal SEP-cover. Our proof gives an alternative proof for the existence of a universal embedding cover of a profinite group. Also our proof works for any full subcategory of the sorted profinite groups, which is closed under taking finite quotients, fibre products, (...) and inverse limits. We also show that any sorted profinite group having SEP has a sorted complete system whose theory is $\omega $ -categorical and $\omega $ -stable under the assumption that the set of sorts is countable. (shrink)

Prominent thinkers such as Jurgen Habermas and Michael Sandel are warning that biomedical enhancements will undermine fundamental political values. Yet whether biomedical enhancements will undermine such values depends on how biomedical enhancements will function, how they will be administered and to whom. Since only few enhancements are obtainable, it is difficult to tell whether these predictions are sound. Nevertheless, such warnings are extremely valuable. As a society we must, at the very least, be aware of developments that could have harmful (...) consequences. Indeed, if important values were to be jeopardized, we should take appropriate measures to protect them. This paper focuses on four central values: solidarity, personal responsibility, equality and autonomy. It delineates the conditions under which biomedical enhancements would undermine these values. It also details the circumstances under which these values would be unaffected by enhancements as well as those under which they would be promoted. Specifying these conditions is valuable; it would enable society to prepare appropriate ethical guidelines and policy responses in advance. (shrink)