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)

This study employed a scenario-based approach whereby participants were asked to choose which communication channel they prefer in certain situations. The first aim was to determine the effect of the topic of interactions and social ties on channel choice. The second aim was to examine the underlying mechanisms in the relation between interaction topic and social ties and channel choice. A questionnaire was administered among 238 participants, who were presented five communication scenarios with topics of low and high intimacy and (...) four social ties, ranging from weak to strong. Results revealed that preference for face-to-face communication was highest, followed by audio-only computer-mediated communication and text-based CMC. Preference for FtF communication was higher when people valued feeling co-present and decreased when people valued feeling anonymous. Our results showed that communication channel choice is strategic and the choice for FtF ommunication, audio-only and text-based CMC largely depends on controllability, anonymity and co-presence. (shrink)

Achieving space situational awareness requires, at a minimum, the identification, characterization, and tracking of space objects. Leveraging the resultant space object data for purposes such as hostile threat assessment, object identification, and conjunction assessment presents major challenges. This is in part because in characterizing space objects we reference a variety of identifiers, components, subsystems, capabilities, vulnerabilities, origins, missions, orbital elements, patterns of life, operational processes, operational statuses, and so forth, which tend to be defined in highly heterogeneous and sometimes inconsistent (...) ways. The Space Domain Ontologies are designed to provide a consensus-based realist framework for formulating such characterizations in a way that is both consistent and computable. Space object data are aligned with classes and relations in a suite of ontologies built around the existing Space Object Ontology. They are stored in a dynamically updated Resource Description Framework triple store, which can be queried to support space situational awareness and the needs of spacecraft operators and analysts. This paper provides an overview of the Space Domain Ontologies and their development and use. It presents the motivation for and advantages of the Space Domain Ontologies, including the benefits they provide for enhancing and maintaining long-term space situational awareness. (shrink)

Despite the frequency of stillbirths, the subsequent implications are overlooked and underappreciated. We present findings from comprehensive, systematic literature reviews, and new analyses of published and unpublished data, to establish the effect of stillbirth on parents, families, health-care providers, and societies worldwide. Data for direct costs of this event are sparse but suggest that a stillbirth needs more resources than a livebirth, both in the perinatal period and in additional surveillance during subsequent pregnancies. Indirect and intangible costs of stillbirth are (...) extensive and are usually met by families alone. This issue is particularly onerous for those with few resources. Negative effects, particularly on parental mental health, might be moderated by empathic attitudes of care providers and tailored interventions. The value of the baby, as well as the associated costs for parents, families, care providers, communities, and society, should be considered to prevent stillbirths and reduce associated morbidity. (shrink)

Biological ontologies are used to organize, curate, and interpret the vast quantities of data arising from biological experiments. While this works well when using a single ontology, integrating multiple ontologies can be problematic, as they are developed independently, which can lead to incompatibilities. The Open Biological and Biomedical Ontologies Foundry was created to address this by facilitating the development, harmonization, application, and sharing of ontologies, guided by a set of overarching principles. One challenge in reaching these goals was that the (...) OBO principles were not originally encoded in a precise fashion, and interpretation was subjective. Here we show how we have addressed this by formally encoding the OBO principles as operational rules and implementing a suite of automated validation checks and a dashboard for objectively evaluating each ontology’s compliance with each principle. This entailed a substantial effort to curate metadata across all ontologies and to coordinate with individual stakeholders. We have applied these checks across the full OBO suite of ontologies, revealing areas where individual ontologies require changes to conform to our principles. Our work demonstrates how a sizable federated community can be organized and evaluated on objective criteria that help improve overall quality and interoperability, which is vital for the sustenance of the OBO project and towards the overall goals of making data FAIR. Competing Interest StatementThe authors have declared no competing interest. (shrink)

This paper argues that higher-order doubt generates an epistemic dilemma. One has a higher-order doubt with regards to P insofar as one justifiably withholds belief as to what attitude towards P is justified. That is, one justifiably withholds belief as to whether one is justified in believing, disbelieving, or withholding belief in P. Using the resources provided by Richard Feldman’s recent discussion of how to respect one’s evidence, I argue that if one has a higher-order doubt with regards to P, (...) then one is not justified in having any attitude towards P. Otherwise put: No attitude towards the doubted proposition respects one’s higher-order doubt. I argue that the most promising response to this problem is to hold that when one has a higher-order doubt about P, the best one can do to respect such a doubt is to simply have no attitude towards P. Higher-order doubt is thus much more rationally corrosive than non-higher-order doubt, as it undermines the possibility of justifiably having any attitude towards the doubted proposition. (shrink)

Let ${2-\textsf{RAN}}$ be the statement that for each real X a real 2-random relative to X exists. We apply program extraction techniques we developed in Kreuzer and Kohlenbach (J. Symb. Log. 77(3):853–895, 2012. doi:10.2178/jsl/1344862165), Kreuzer (Notre Dame J. Formal Log. 53(2):245–265, 2012. doi:10.1215/00294527-1715716) to this principle. Let ${{\textsf{WKL}_0^\omega}}$ be the finite type extension of ${\textsf{WKL}_0}$ . We obtain that one can extract primitive recursive realizers from proofs in ${{\textsf{WKL}_0^\omega} + \Pi^0_1-{\textsf{CP}} + 2-\textsf{RAN}}$ , i.e., if ${{\textsf{WKL}_0^\omega} + \Pi^0_1-{\textsf{CP}} + 2-\textsf{RAN} (...) \, {\vdash} \, \forall{f}\, {\exists}{x} A_{qf}(f,x)}$ then one can extract from the proof a primitive recursive term t(f) such that ${A_{qf}(f,t(f))}$ . As a consequence, we obtain that ${{\textsf{WKL}_0}+ \Pi^0_1 - {\textsf{CP}} + 2-\textsf{RAN}}$ is ${\Pi^0_3}$ -conservative over ${\textsf{RCA}_0}$. (shrink)

Family income is associated with gray matter morphometry in children, but little is known about the relationship between family income and white matter structure. In this paper, using Tract-Based Spatial Statistics (TBSS), a whole brain, voxel-wise approach, we examined the relationship between family income (assessed by income-to-needs ratio) and white matter organization in middle childhood (N = 27, M = 8.66 years). Results from a nonparametric, voxel-wise, multiple regression (threshold-free cluster enhancement, p < 0.05, FWE corrected) indicated that lower family (...) income was associated with lower white matter organization (assessed by fractional anisotropy) for several clusters in white matter tracts involved in cognitive and emotional functions including fronto-limbic circuitry (uncinate fasciculus and cingulum bundle), association fibers (inferior longitudinal fasciculus, superior longitudinal fasciculus), and corticospinal tracts. Further, we examined the possibility that cumulative risk exposure might function as one of the potential pathways by which family income influences neural outcomes. Using multiple regressions, we found lower fractional anisotropy in portions of these tracts, including those found in the left cingulum bundle and left superior longitudinal fasciculus, was significantly related to greater exposure to cumulative risk (β = -0.47, p < 0.05 and β = -0.45, p < 0.05). (shrink)

Most donated organs in the United States come from brain dead donors, while a small percentage come from patients who die in “controlled,” or expected, circumstances, typically after the family or surrogate makes a decision to withdraw life support. The number of organs available for transplant could be substantially if donations were permitted in “uncontrolled” circumstances–that is, from people who die unexpectedly, often outside the hospital. According to projections from the Institute of Medicine, establishing programs permitting “uncontrolled donation after circulatory (...) determination of death,” or uDCDD, throughout the United States has the potential to provide 22,000 more donation opportunities annually. In contrast, U.S. controlled donation after circulatory determination of death, or cDCDD, cases have increased progressively over the past decade from 87 to 848 donors, but currently account for only 10.6 percent of all deceased donors. Following the IOM recommendations, several projects exploring the feasibility of uDCDD were funded by the federal government, including a grant from the Health Resources and Services Administration that supported a pilot project in New York City in which the authors of this article participated.A key feature of our protocol, and indeed of many uDCDD protocols, is the initiation of preservation methods such as chest compressions and extracorporeal membrane oxygenation shortly after death in order to perfuse and preserve the donor's organs. Critics of uDCDD argue that the means of determining death deviates from generally ascribed principles. They assert that reinstituting circulation in order to preserve organs has the effect of “undoing” the prior determination of death. The result is that cDCDD is widely accepted and practiced routinely even though it only marginally increases the number of organs available for transplantation, and uDCDD is widely considered unacceptable despite being ethically embraced and proven to significantly increase organ donation opportunities in other countries. This article explores the evolution of this counterintuitive state of affairs and calls for a policy that, in line with the IOM report, allows for both cDCDD and uDCDD protocols. (shrink)

J. Kaerst, following a suggestion made by Ranke, conjectured that Diodorus' source for Alexander, whom he identified with Clitarchus, derived information from the mercenaries who served Darius. This conjecture has been developed into an elaborate theory by Sir William Tarn, a theory that has found some favour. He holds that the ‘mercenaries' source’, which I shall henceforth call M, was Diodorus' ‘principal guide [my italics] down to Issus’, and also ‘largely used’ by Curtius ; from certain texts in Curtius (...) Tarn infers that M went down to Darius' death, and he thinks that till that point both Diodorus and Curtius continued to draw upon him, as well as upon other authorities. (shrink)