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)

Aspects of Northoff's argument lend themselves to the ongoing investigation of localizing the self in the brain. Recent data from the fields of neuropsychology and cognitive neuroscience provide evidence that the right hemisphere is a candidate for localization of self. The data on catatonia further that proposition and add insight into the continuing investigation of self in the brain across sensory and motor domains.

For all of the emphasis on quality improvement—as well as the acknowledged overlap between assessment of the quality of healthcare services and clinical ethics—the quality of clinical ethics consultation has received scant attention, especially in terms of empirical measurement. Recognizing this need, the second edition of Core Competencies for Health Care Ethics Consultation identified four domains of ethics quality: (1) ethicality, (2) stakeholders’ satisfaction, (3) resolution of the presenting conflict/dilemma, and (4) education that translates into knowledge. This study is the (...) first, to our knowledge, to directly measure all of these domains. Here we describe the quality improvement process undertaken at a tertiary care academic medical center, as well as the tools developed to measure the quality of ethics consultation, which include post-consultation satisfaction surveys and weekly case conferences. The information gained through these tools helps to improve not only the process of ethics consultation, but also the measurement and assurance of quality. (shrink)

Live donor kidney transplantation is the best treatment option for most patients with late-stage chronic kidney disease; however, the rate of living kidney donation has declined in the United States. A consensus conference was held June 5-6, 2014 to identify best practices and knowledge gaps pertaining to live donor kidney transplantation and living kidney donation. Transplant professionals, patients, and other key stakeholders discussed processes for educating transplant candidates and potential living donors about living kidney donation; efficiencies in the living donor (...) evaluation process; disparities in living donation; and financial and systemic barriers to living donation. We summarize the consensus recommendations for best practices in these educational and clinical domains, future research priorities, and possible public policy initiatives to remove barriers to living kidney donation. (shrink)

Transcription factor (TF) signaling regulates gene transcription and requires a complex network of proteins. This network includes co‐activators, co‐repressors, multiple TFs, histone‐modifying complexes, and the basal transcription machinery. It has been widely appreciated that pioneer factors, such as FoxA1 and GATA1, play an important role in opening closed chromatin regions, thereby allowing binding of a secondary factor. In this review we will focus on a newly proposed model wherein multiple TFs, such as steroid receptors (SRs), can function in a pioneering (...) role. This model, termed dynamic assisted loading, integrates data from widely divergent methodologies, including genome wide ChIP‐Seq, digital genomic footprinting, DHS‐Seq, live cell protein dynamics, and biochemical studies of ATP‐dependent remodeling complexes, to present a real time view of TF chromatin interactions. Under this view, many TFs can act as initiating factors for chromatin landscape programming. Furthermore, enhancer and promoter states are more accurately described as energy‐dependent, non‐equilibrium steady states. (shrink)

Numerous searches have failed to identify a single co-occurrence of total blindness and schizophrenia. Evidence that blindness causes loss of certain NMDA-receptor functions is balanced by reports of compensatory gains. Connections between visual and anterior cingulate NMDA-receptor systems may help to explain how blindness could protect against schizophrenia.

The US neutrino community gathered at the Workshop on the Intermediate Neutrino Program at Brookhaven National Laboratory February 4-6, 2015 to explore opportunities in neutrino physics over the next five to ten years. Scientists from particle, astroparticle and nuclear physics participated in the workshop. The workshop examined promising opportunities for neutrino physics in the intermediate term, including possible new small to mid-scale experiments, US contributions to large experiments, upgrades to existing experiments, R&D plans and theory. The workshop was organized into (...) two sets of parallel working group sessions, divided by physics topics and technology. Physics working groups covered topics on Sterile Neutrinos, Neutrino Mixing, Neutrino Interactions, Neutrino Properties and Astrophysical Neutrinos. Technology sessions were organized into Theory, Short-Baseline Accelerator Neutrinos, Reactor Neutrinos, Detector R&D and Source, Cyclotron and Meson Decay at Rest sessions.This report summarizes discussion and conclusions from the workshop. (shrink)

Individual differences in the mere willingness to think analytically has been shown to predict religious disbelief. Recently, however, it has been argued that analytic thinkers are not actually less religious; rather, the putative association may be a result of religiosity typically being measured after analytic thinking (an order effect). In light of this possibility, we report four studies in which a negative correlation between religious belief and performance on analytic thinking measures is found when religious belief is measured in a (...) separate session. We also performed a meta-analysis on all previously published studies on the topic along with our four new studies (N = 15,078, k = 31), focusing specifically on the association between performance on the Cognitive Reflection Test (the most widely used individual difference measure of analytic thinking) and religious belief. This meta-analysis revealed an overall negative correlation (r) of -.18, 95% CI [-.21, -.16]. Although this correlation is modest, self-identified atheists (N = 133) scored 18.7% higher than religiously affiliated individuals (N = 597) on a composite measure of analytic thinking administered across our four new studies (d = .72). Our results indicate that the association between analytic thinking and religious disbelief is not caused by a simple order effect. There is good evidence that atheists and agnostics are more reflective than religious believers. (shrink)

The timely feature article by van der Pijl et al 1 highlights not only the widespread frequency with which unconsented episiotomies and other procedures during labour are reported by women but also that there is hardly any discussion in the literature on the ethics of consent for procedures in labour. Those national and international bodies with responsibility for midwifery and obstetric practice need not only to recognise but also act to remedy this unacceptable situation. The studies quoted used the recollection (...) of women in reporting consent or lack of it and, although this is an entirely appropriate measure, it gives no insight into what, if any, informed decision-making the care providers carried out. Such information would be useful to determine how better practice might be achieved. A study into the practice of episiotomies by Dutch midwives and obstetricians is referred to and is not reassuring.2 They frequently expressed surprise that consent should be necessary and women were minimally involved in the decision for performing episiotomy. This and other examples quoted of lack of valid consent have a corrosive effect on the fundamental but fragile trust and necessary trustworthiness of the relationship between the person being cared for …. (shrink)

Robust stakeholder engagement in health research requires broad communicative integration, not only of patients but also other stakeholders such as health system leaders, clinicians, and researcher...

Teaching and learning of medical ethics and law are at the heart of medical education because they are integral to all clinical encounters and public health interventions, and a foundation in medical ethics and law is essential for students to become virtuous doctors. The first model curriculum for medical ethics and law within medical education in the UK, published in 1998, has recently been reviewed and updated. Now called a core content of learning, it emphasizes that teaching and learning of (...) medical ethics and law should be attuned to the students' needs appropriate both to their particular stage of training and to relevant specialty-specific ethical issues; is a shared obligation of all teachers throughout the course; and should be integrated vertically and horizontally throughout the whole medical curriculum. The General Medical Council and the British Medical Association have confirmed that the revised core content of learning is consistent with their guidance on undergraduate education. (shrink)

Mindreading (or folk psychology, Theory of Mind, mentalizing) is the capacity to represent and reason about others’ mental states. The Simulation Theory (ST) is one of the main approaches to mindreading. ST draws on the common-sense idea that we represent and reason about others’ mental states by putting ourselves in their shoes. More precisely, we typically arrive at representing others’ mental states by simulating their mental states in our own mind. This entry offers a detailed analysis of ST, considers theoretical (...) arguments and empirical data in favour of and against it, discusses its philosophical implications, and illustrates some alternatives to it. (shrink)

While many "benchtop-to-bedside" research pathways have been developed in "Type I" translational medicine, vehicles to facilitate "Type II" and "Type III" translation that convert scientific data into clinical and community interventions designed to improve the health of human populations remain elusive. Further, while a high percentage of physicians endorse the principle of citizen leadership, many have difficulty practicing it. This discrepancy has been attributed, in part, to lack of training and preparation for public advocacy, time limitation, and institutional resistance. As (...) translational medicine and physician-citizenship implicate social, political, economic and cultural factors, both enterprises require "integrative" research strategies that blend insights from multiple fields of study, as well as rhetorical acumen in adapting messages to reach multiple audiences. This article considers how argumentation theory's epistemological flexibility, audience attentiveness, and heuristic qualities, combined with concepts from classical rhetoric, such as rhetorical invention, the synecdoche, and ethos, yield tools to facilitate translational medicine and enable physician-citizenship. (shrink)