v. 1. Nicomachean ethics. Politics. The Athenian Constitution. Rhetoric. On Poetics.--v. 2. Logic.--v. 3. Physics. Metaphysics. On the soul. Short physical treaties.--v. 4. On the heavens. On generation and corruption. Meteorology. Biological treatises.

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)

Clinical ethics consultation is largely outside the scope of regulation and oversight, despite its importance. For decades, the bioethics community has been unable to reach a consensus on whether there should be accountability in this work, as there is for other clinical activities that influence the care of patients. The American Society for Bioethics and Humanities, the primary society of bioethicists and scholars in the medical humanities and the organizational home for individuals who perform CEC in the United States, has (...) initiated a two‐step quality attestation process as a means to assess clinical ethics consultants and help identify individuals who are qualified to perform this role. This article describes the process. (shrink)

While outcomes for children with T-cell acute lymphoblastic leukemia have improved dramatically, survival rates for patients with relapsed/refractory disease remain dismal. Prior studies indicate that glucocorticoid resistance is more common than resistance to other chemotherapies at relapse. In addition, failure to clear peripheral blasts during a prednisone prophase correlates with an elevated risk of relapse in newly diagnosed patients. Here we show that intrinsic GC resistance is present at diagnosis in early thymic precursor T-ALLs as well as in a subset (...) of non-ETP T-ALLs. GC-resistant non-ETP T-ALLs are characterized by strong induction of JAK/STAT signaling in response to interleukin-7 stimulation. Removing IL7 or inhibiting JAK/STAT signaling sensitizes these T-ALLs, and a subset of ETP T-ALLs, to GCs. The combination of the GC dexamethasone and the JAK1/2 inhibitor ruxolitinib altered the balance between pro- and anti-apoptotic factors in samples with IL7-dependent GC resistance, but not in samples with IL7-independent GC resistance. Together, these data suggest that the addition of ruxolitinib or other inhibitors of IL7 receptor/JAK/STAT signaling may enhance the efficacy of GCs in a biologically defined subset of T-ALL.Leukemia advance online publication, 30 May 2017; doi:10.1038/leu.2017.136. (shrink)

We have synthesized a 582,970-base pair Mycoplasma genitalium genome. This synthetic genome, named M. genitalium JCVI-1.0, contains all the genes of wild-type M. genitalium G37 except MG408, which was disrupted by an antibiotic marker to block pathogenicity and to allow for selection. To identify the genome as synthetic, we inserted "watermarks" at intergenic sites known to tolerate transposon insertions. Overlapping "cassettes" of 5 to 7 kilobases (kb), assembled from chemically synthesized oligonucleotides, were joined by in vitro recombination to produce intermediate (...) assemblies of approximately 24 kb, 72 kb ("1/8 genome"), and 144 kb ("1/4 genome"), which were all cloned as bacterial artificial chromosomes in Escherichia coli. Most of these intermediate clones were sequenced, and clones of all four 1/4 genomes with the correct sequence were identified. The complete synthetic genome was assembled by transformation-associated recombination cloning in the yeast Saccharomyces cerevisiae, then isolated and sequenced. A clone with the correct sequence was identified. The methods described here will be generally useful for constructing large DNA molecules from chemically synthesized pieces and also from combinations of natural and synthetic DNA segments. 10.1126/science.1151721. (shrink)

This book's importance is derived from three sources: careful conceptualization of teacher induction from historical, methodological, and international perspectives; systematic reviews of research literature relevant to various aspects of teacher induction including its social, cultural, and political contexts, program components and forms, and the range of its effects; substantial empirical studies on the important issues of teacher induction with different kinds of methodologies that exemplify future directions and approaches to the research in teacher induction.

The National Center for Biomedical Ontology is a consortium that comprises leading informaticians, biologists, clinicians, and ontologists, funded by the National Institutes of Health (NIH) Roadmap, to develop innovative technology and methods that allow scientists to record, manage, and disseminate biomedical information and knowledge in machine-processable form. The goals of the Center are (1) to help unify the divergent and isolated efforts in ontology development by promoting high quality open-source, standards-based tools to create, manage, and use ontologies, (2) to create (...) new software tools so that scientists can use ontologies to annotate and analyze biomedical data, (3) to provide a national resource for the ongoing evaluation, integration, and evolution of biomedical ontologies and associated tools and theories in the context of driving biomedical projects (DBPs), and (4) to disseminate the tools and resources of the Center and to identify, evaluate, and communicate best practices of ontology development to the biomedical community. Through the research activities within the Center, collaborations with the DBPs, and interactions with the biomedical community, our goal is to help scientists to work more effectively in the e-science paradigm, enhancing experiment design, experiment execution, data analysis, information synthesis, hypothesis generation and testing, and understand human disease. (shrink)

Are contemporary philosophers to follow Pyrrho of Elis in adopting his skeptic craft or at least core aspects of it as a reaction to the fact that, since immemorial times, persons have been engaged in disputes in metaphysics? Over the last 2500 years or so, most Western philosophers have not done so in being more influenced by Aristotle’s dogmatic craft than by Pyrrho’s skeptic one. Over the last fifty years or so, a few Brazilian neo-Pyrrhonist philosophers, such as Oswald Porchat, (...) Otávio Bueno and Plínio Junqueira Smith, have done the opposite in aiming to spell out the pertinence of Ancient Pyrrhonism to contemporary philosophy. On its part, this essay makes a case for the claim that one is to react to the stated fact by adopting a conflictual craft that promotes a synthesis of Pyrrho’s skeptic craft and the dogmatic craft. This synthesis: brings to light the core features of the skeptic and of the dogmatic craft; problematizes the dogmatic craft by means of the skeptic one and vice-versa so that the shortcomings of these crafts are avoided; and aims to keep certain positive aspects both of the skeptic craft and of the dogmatic one. (shrink)

The COVID-19 pandemic revealed numerous weaknesses in pandemic preparedness and response, including underfunding, inadequate surveillance, and inequitable distribution of countermeasures. To overcome these weaknesses for future pandemics, WHO released a zero draft of a pandemic treaty in February, 2023, and subsequently a revised bureau's text in May, 2023. COVID-19 made clear that pandemic prevention, preparedness, and response reflect choices and value judgements. These decisions are therefore not a purely scientific or technical exercise, but are fundamentally grounded in ethics. The latest (...) treaty draft reflects these ethical considerations by including a section entitled Guiding Principles and Approaches. Most of these principles are ethical—they establish core values that undergird the treaty. Unfortunately, the treaty draft's set of principles are numerous, overlapping, and show inadequate coherence and consistency. We propose two improvements to this section of the draft pandemic treaty. First, key guiding ethical principles should be clearer and more precise than they currently are. Second, the link between ethical principles and policy implementation should be clearly established and define boundaries on acceptable interpretation, ensuring that signatories abide by these principles. (shrink)

Philosophers and other scholars have often claimed that the arts are not only cognitively valuable but also morally improving (e.g., Nussbaum, 1997). However, their arguments often proceed with little attention to empirical evidence. At the same time, filmmakers and media creators deliberately use devices to direct their audience’s attention, with the intention of impacting viewers’ cognitive, affective, and neurological responses in meaningful ways (Carroll & Seeley, 2013). Whether these devices have the desired effects, and on whom, also remains largely untested. (...) If we want to understand the ways that film and media can have moral impacts, we must step out of our disciplinary siloes. It is not enough for film experts, philosophers, and experimentalists to merely take note of each other’s work; collaborative interdisciplinary research is required, both to improve methods and to examine questions that have not yet been empirically explored. In this article we propose a model for this kind of research, focusing on how media can influence moral understanding. We first outline the challenges that must be met for such research to be successful, including clarifying and operationalizing concepts, measuring moral understanding, and applying empirical methods to media and the arts. We then describe the advantages of interdisciplinary collaboration for meeting these challenges, in the context of some recent examples of interdisciplinary projects on related themes. (shrink)

Both the theory that traumatic childhood memories can be repressed, and the reliability of the techniques used to retrieve these memories are challenged in this paper. Questions are raised about the robustness of the theory and the literature that purports to provide scientific evidence for it. Evidence to this end is provided by the demographic and qualitative results of a research study conducted by the authors which surveyed New Zealand families in which one member had accused another of sexual abuse (...) on the basis of recovered memories. It is shown that a number of these allegations involve very low probability events. Since memory repression theory is not currently scientifically substantiated it is argued that care needs to be taken in the mental health, legal and insurance compensation arenas. Memories recalled during therapy may be treated as metaphorical but, in the absence of corroborative evidence, should not be considered factually true. Clinicians who wish to use memory recovery techniques should inform patients of their experimental and controversial nature, point out potential adverse effects, and obtain consent before proceeding. (shrink)

Mill's feminism has been attacked as being logically incoherent. The general verdict has been that Mill can easily be defended from the charge. However, both sides in the debate have ignored the fact that his feminism is part of a broader theory of liberal empiricism. Placing The Subjection of Women in this context re–opens the question of its logical credentials and reveals a basic weakness in Millian feminism.

A medical information commons is a networked data environment utilized for research and clinical applications. At three deliberations across the U.S., we engaged 75 adults in two-day facilitated discussions on the ethical and social issues inherent to sharing data with an MIC. Deliberants made recommendations regarding opt-in consent, transparent data policies, public representation on MIC governing boards, and strict data security and privacy protection. Community engagement is critical to earning the public's trust.

Synthetic biology, as a research field, brings together molecular life scientists, computational biologists, and social scientists to engineer biological systems toward societally desired goals. Given the field’s broad multidisciplinarity and relatively young age, innovative educational methods are required to provide students with the needed background knowledge to push the field forward in the future. The international Genetically Engineered Machine competition is such an example where education and high-level research merge, providing the synthetic biology field with trained students, new ideas, and (...) novel results. In the 2021 edition alone, 343 teams from across the world completed the competition to tackle societal problems with synthetic biology. As Wageningen University & Research celebrates 10 years of participation in iGEM, we share our thoughts and experiences on supervising iGEM teams, which is especially relevant to organizers of current and new teams, and also others interested in the iGEM competition. (shrink)

A theoretical framework Is presented that distinguishes among three knowledge sources that form the basis for generative performance. The three knowledge sources, termed conceptual, procedural, and utilizational competence, were implemented as a computational model that derives plans for counting procedures. In a previous analysis, Greeno, Riley, and Gelman (1984) developed a characterization of the conceptual competence (implicit understanding of general concepts and principles) associated with the skill of counting and related conceptual competence to various models of performance. In the current (...) work all three knowledge sources are formalized in a computer program (COUNTPLAN) that generates planning nets of counting procedures. The sufficiency of COUNTPLAN's knowledge components is demonstrated through its capacity to generate new plans for counting in novel settings from a core of conceptual competence. The utility of COUNTPLAN to facilitate the distinction between hypotheses of competence and hypotheses of performance is discussed. (shrink)

The aim of this article is to examine some of the consequences of the recent advances in neurobiology in terms of the ability of drugs to manipulate the mind. Most laymen are totally ignorant of the general mechanism underlying the brain-mind relationship and therefore of the action of mind-altering drugs. Professor Grahame-Smith considers that one of the intrinsic evils of man's neurobiological make up is that a prime motive of the brain seems to be to bring comfort, security and (...) pleasure for itself. Therefore it is not surprising that drugs - notably the barbiturates and more recently the benzodiazepines (tranquilizers) - have been prescribed to give to the brain that peace of mind that it seeks. However, it can be argued that such drugs cannot replace anxiety with peace of mind or unhappiness or depression with happiness. The action of such drugs upon the molecules of the brain is negative - a placebo effect. (shrink)

Writing in the foreword to Allan Bloom's The Closing of the American Mind and speaking of his upbringing in Chicago between the wars Saul Bellow attests that …as a Midwesterner, the son of immigrant parents, I recognized at an early stage that I was called upon to decide for myself to what extent my Jewish origins, my surroundings [‘the accidental circumstances of Chicago’], my schooling, were to be allowed to determine the course of my life. I did not intend to (...) be wholly dependent upon history and culture. Full dependency must mean that I was done for. The commonest teaching of the civilized world in our time can be stated simply: ‘Tell me where you come from and I'll tell you what you are’. (shrink)

This commentary examines the role of sustainability in the latest draft of the WHO pandemic accord, highlighting its notable absence from the official list of guiding principles despite being mentioned frequently throughout the text. It argues that sustainability should be explicitly acknowledged as a core principle and given a clear definition tailored to pandemic preparedness, and proposes defining sustainability as ensuring that immediate emergency responses don't compromise future pandemic preparedness and response capabilities. Including sustainability as a guiding principle would serve (...) two key purposes: validating the relevance of ethical principles in the accord's provisions and emphasizing the importance of long-term planning in pandemic preparedness. The commentary notes that while humans naturally discount future consequences, sustainable pandemic planning requires considering impacts beyond the next pandemic. It recommends coupling any reforms, such as intellectual property changes, with alternative innovation incentives to maintain a balanced approach to pandemic preparedness and response. (shrink)

In this book, Steven G. Smith focuses on the guidance function in language and scripture and evaluates the assumptions and ideals of scriptural religion in global perspective. He brings to language studies a new pragmatic emphasis on the shared modeling of life-in-the-world by communicators constantly depending on each other's guidance. Using concepts of axiality and axialization derived from Jaspers' description of the 'Axial Age', he shows the essential role of scripture in the historical progress of communicative action. This volume (...) clarifies the formative power of scriptures in religions of the 'world religion' type and brings scripture into philosophy of religion as a major cross-cultural category of study, thereby helping philosophy of religion find a needed cross-cultural footing. (shrink)

ABSTRACT Real-time graphical interval logic is a modal logic for reasoning about time in which the basic modality is the interval. The logic differs from other logics in that it has a natural intuitive graphical representation that resembles the timing diagrams drawn by system designers. We have developed an automted deduction system for the logic, which includes a theorem prover and a user interface. The theorem prover checks the validity of proofs in the logic and produces counterexamples to invalid proofs. (...) The user interface includes a graphical editor that enables the user to create graphical formulas on a workstation display, and a database and proof manager that tracks proof dependencies and allows graphical formulas to be stored and retrieved. In this paper we describe the logic, the automated deduction system, and an application to robotics. (shrink)