The integration of biomedical terminologies is indispensable to the process of information integration. When terminologies are linked merely through the alignment of their leaf terms, however, differences in context and ontological structure are ignored. Making use of the SNAP and SPAN ontologies, we show how three reference domain ontologies can be integrated at a higher level, through what we shall call the OBR framework (for: Ontology of Biomedical Reality). OBR is designed to facilitate inference across the boundaries of domain ontologies (...) in anatomy, physiology and pathology. (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)

The Common Anatomy Reference Ontology (CARO) is being developed to facilitate interoperability between existing anatomy ontologies for different species, and will provide a template for building new anatomy ontologies. CARO has a structural axis of classification based on the top-level nodes of the Foundational Model of Anatomy. CARO will complement the developmental process sub-ontology of the GO Biological Process ontology, using it to ensure the coherent treatment of developmental stages, and to provide a common framework for the model organism communities (...) to classify developmental structures. Definitions for the types and relationships are being generated by a consortium of investigators from diverse backgrounds to ensure applicability to all organisms. CARO will support the coordination of cross-species ontologies at all levels of anatomical granularity by cross-referencing types within the cell type ontology (CL) and the Gene Ontology (GO) Cellular Component ontology. A complete cross-species CARO could be utilized in other ontologies for cross-product generation. (shrink)

This interview, conducted over the span of several months, tracks the respective journeys of Constantin V. Boundas and Daniel W. Smith with the philosophy of Gilles Deleuze. Rather than “becoming Deleuzian,” which is neither desirable nor possible, these exchanges reflect an array of encounters with Deleuze. These include the initial discoveries of Deleuze’s writings by Boundas and Smith, in-person meetings between Boundas and Deleuze, and the wide-ranging and influential philosophical work on Deleuze’s concepts produced by both Boundas and (...) Smith. At stake in this discussion are key contributions by Deleuze to continental philosophy, including the distinction between the virtual and the actual and the very nature of a “concept.” Also at stake is the formative or pedagogical impact of a philosopher, like Deleuze, on those who find and fully engage with his texts, concepts, and project. Cette interview, menée sur plusieurs mois, suit les parcours respectifs de Constantin V. Boundas et Daniel W. Smith avec la philosophie de Gilles Deleuze. Au lieu de « devenir Deleuzien, » ce qui n’est ni souhaitable ni possible, ces échanges reflètent un éventail de rencontres avec Deleuze. Il s’agit notamment des premières découvertes des écrits de Deleuze par Boundas et Smith, des rencontres en personne entre Boundas et Deleuze, et du travail philosophique vaste et in????luent sur les concepts de Deleuze produit par Boundas et Smith. L’enjeu ici étant les contributions clés de Deleuze à la philosophie continentale, y compris la distinction entre le virtuel et l’actuel, et la nature même d’un « concept. » Mais il y a aussi l’impact formateur ou pédagogique d’un philosophe, comme Deleuze, sur ceux qui trouvent et s’engagent pleinement dans ses textes, ses concepts et ses projets. (shrink)

The objective of the study was to investigate the relationship between childhood IQ of parents and characteristics of their adult offspring. It was a prospective family cohort study linked to a mental ability survey of the parents and set in Renfrew and Paisley in Scotland. Participants were 1921-born men and women who took part in the Scottish Mental Survey in 1932 and the Renfrew/Paisley study in the 1970s, and whose offspring took part in the Midspan Family study in 1996. There (...) were 286 offspring from 179 families. Parental IQ was related to some, but not all characteristics of offspring. Greater parental IQ was associated with taller offspring. Parental IQ was inversely related to number of cigarettes smoked by offspring. Higher parental IQ was associated with better education, offspring social class and offspring deprivation category. There were no significant relationships between parental IQ and offspring systolic blood pressure, diastolic blood pressure, cholesterol, glucose, lung function, weight, body mass index, waist hip ratio, housing, alcohol consumption, marital status, car use and exercise. Structural equation modelling showed parental IQ associated with offspring education directly and mediated via parental social class. Offspring education was associated with offspring smoking and social class. The smoking finding may have implications for targeting of health education. (shrink)

Host-microbiome interactions (HMIs) are critical for the modulation of biological processes and are associated with several diseases, and extensive HMI studies have generated large amounts of data. We propose that the logical representation of the knowledge derived from these data and the standardized representation of experimental variables and processes can foster integration of data and reproducibility of experiments and thereby further HMI knowledge discovery. A community-based Ontology of Host-Microbiome Interactions (OHMI) was developed following the OBO Foundry principles. OHMI leverages established (...) ontologies to create logically structured representations of microbiomes, microbial taxonomy, host species, host anatomical entities, and HMIs under different conditions and associated study protocols and types of data analysis and experimental results. (shrink)

We congratulate Fox and her colleagues (2007) for contributing to the published empirical literature on ethics consultation in United States hospitals. Their study demonstrates the continued wide v...

BackgroundIn the Canadian Alliance for Healthy Hearts and Minds (CAHHM) cohort, participants underwent magnetic resonance imaging (MRI) of the brain, heart, and abdomen, that generated incidental findings (IFs). The approach to managing these unexpected results remain a complex issue. Our objectives were to describe the CAHHM policy for the management of IFs, to understand the impact of disclosing IFs to healthy research participants, and to reflect on the ethical obligations of researchers in future MRI studies.MethodsBetween 2013 and 2019, 8252 participants (...) (mean age 58 ± 9 years, 54% women) were recruited with a follow-up questionnaire administered to 909 participants (40% response rate) at 1-year. The CAHHM policy followed a restricted approach, whereby routine feedback on IFs was not provided. Only IFs of severe structural abnormalities were reported.ResultsSevere structural abnormalities occurred in 8.3% (95% confidence interval 7.7–8.9%) of participants, with the highest proportions found in the brain (4.2%) and abdomen (3.1%). The majority of participants (97%) informed of an IF reported no change in quality of life, with 3% of participants reporting that the knowledge of an IF negatively impacted their quality of life. Furthermore, 50% reported increased stress in learning about an IF, and in 95%, the discovery of an IF did not adversely impact his/her life insurance policy. Most participants (90%) would enrol in the study again and perceived the MRI scan to be beneficial, regardless of whether they were informed of IFs. While the implications of a restricted approach to IF management was perceived to be mostly positive, a degree of diagnostic misconception was present amongst participants, indicating the importance of a more thorough consent process to support participant autonomy.ConclusionThe management of IFs from research MRI scans remain a challenging issue, as participants may experience stress and a reduced quality of life when IFs are disclosed. The restricted approach to IF management in CAHHM demonstrated a fair fulfillment of the overarching ethical principles of respect for autonomy, concern for wellbeing, and justice. The approach outlined in the CAHHM policy may serve as a framework for future research studies.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/nct02220582. (shrink)

This article is part of a For-Discussion-Section of Methods of Information in Medicine about the paper "Biomedical Informatics: We Are What We Publish", written by Peter L. Elkin, Steven H. Brown, and Graham Wright. It is introduced by an editorial. This article contains the combined commentaries invited to independently comment on the Elkin et al. paper. In subsequent issues the discussion can continue through letters to the editor.

The House of Lords majority decision in Matthews v. Kent and Medway Towns Fire Authority overturns the narrow interpretation given to key aspects of the Part-Time Workers (Protection of Less Favourable Treatment) Regulations’ core comparator mechanism in the lower tribunals and the Court of Appeal. It is a contextually astute judgment, which recognises the reductionist implications of an overly narrow approach to establishing comparability for the purposes of a less favourable treatment claim on the grounds of part-time work. The positive (...) aspect of this decision remains overshadowed, however, by the fact that this interpretation provides little consolation to the large majority of part-time women workers whose disadvantage and inequality remains outside the scope of the Regulations’ protection. (shrink)

This review identifies at least six different kinds of fellow-feeling in Adam Smith’s Theory of Moral Sentiments. The six kinds are (i) the mirroring of emotions; (ii) altruism; (iii) judgment of pitch of emotions/actions; (iv) judgment of merit of emotions/actions; (v) friendship-and-love; and (vi) aspiration that leads to admiration. Smith does not list them side-by-side. This side-by-side listing promises to help thinkers to see how to assemble them to construct a coherent and systematic framework on how to amalgamate (...) three moments of behavior: the emotional, the rational, and the moral. (shrink)

Religion and Community: Adam Smith on the Virtues of Liberty CHARLES L. GRISWOLD, JR. The good temper and moderation of con- tending factions seems to be the most es- gential circumstance in the publick morals of a free people. Adam Smith' THE ARCHITECTS of what one might call "classical" or "Enlightenment" liberal- ism saw themselves as committed to refuting the claims to political sovereignty by organized religion. ~ The arguments against the legitimacy of a state- supported religion, and, (...) in the extreme case, of a religious monopoly, are so integral a part of the Enlightenment's effort to put politics on a stable and just foundation as to constitute one of the controlling themes of the period. Lib- eral politics requires toleration, or better, liberty of religious belief. And this in turn requires that religious institutions be privatized, as it were, and that just politics be secularized in that legitimate rule is to lie in the consent of the ruled rather than in the laws of God as interpreted by his ministers on earth. Differ- ' Wealth of Nations V.i.f.4o. My references to The Wealth of Nations are to the two-volume R. H. Campbell and A. S. Skinner edition . 2 The list of thinkers in the "classical liberal" tradition simply reads as the list of key Enlighten- ment figures: Bayle, Hobbes, Locke, Spinoza, Hume, Smith, Voltaire, and Kant, to name a few. Consider the role that religious freedom plays in Kant's. (shrink)

v. 1. 1737-1756, lettres 1-249 -- v. 2. 1757-1760, lettres 250-464 -- v. 3.1761-1774, lettres 465-720 -- v. 4. 1774-1800, lettres 721-855 -- v. 5. Quatre nouvelles lettres, errata, additions et modifications, lettres exclues de l'édition proprement dite, généalogies, liste des lettres, index et table des matières.

This case note considers the availability in the United Kingdom of the provocation defence in cases of intimate homicide in the context of the recent House of Lords decision in Rv. Smith [2000] 3 W.L.R. 654. The note argues that the expansion of the objective component of the defence to encompass the mental infirmities of individual defendants is dangerous for women. Although it has the potential to help some abused women who kill to use the defence, it has, at (...) the same time, exposed women who are abused by sexually possessive, violent men to even greater danger. It is thus argued that the defence should be restricted in the way envisaged by the minority judgement of Lord Millett so that abused women will still be able to use the defence, but by anon-medical route. Alternatively, the defence should be abolished and defences which pose no risk of encompassing violent men should be developed to accommodate abused women. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:THE MUNUS OF TRANSMITTING HUMAN LIFE: A NEW APPROACH TO I-IUMANAE VITAE JANET E. SMITH University of Dallas Irving, Texas 'TIRE ONLY ACQUAINTANCE 1bhat most rea;ders have with the Latin of Humanae Vitae is the tit1le. It is likey that fow laymen and perhaps eV'en fow schofars make ire:ferenoe to the Latin text; indeed, it is ireported that I-Iumanae Vitae was originally composed in ltalian, and it seems (...) that aH available translations of the text al'e based primarily on the Italian V'ersion. But since the official text of Humanae Vitae is in Latin and since translations are necessa11ily deficient, we shouild not be surprised that the ava:ilahle translations fail to convey a:M the nuances of the official text. (Latin, of course, is tihe langua:ge in which all official documents of the Church are written.) This study seeks to show that attenti¥eness to certain words fa the Latin text, most particularly the word munus, uncovers important eonnections between Humanae Vitae and pe['spect[ves of the Church, perspectives particularly highlighted in the documents of Vatican II. It also seeks to show that the La.tin provides greater philosophical precision for certain key teaohings of the text, most particularly section 11: "each and every maritail act must remain open to proc11eation." It is ii.mportant to note that some of the crucial Latin words of the document cal'ry connotations tihat cannot possibly be captured ihy 1any one English word. Indeed, some of the words convey concepts and attitudes that are quite foreign to speak:iers of modern English; to convey the meaning of some terms requires a. fairly lengthy expl,ication of notions not immed :iate1ly and directly graspaible hy ail readers. Even to the reade[' of Latin, the text does not 'easily ~eld its secrets. The 385 386 JANET E. SMITH Latin of the document has no identifiahle souTee of reliabJe deoipherment; it is a kind of " modern " 0 1 r " Church " Latin, which is an odd comhinat~on of elassical Latin and the lang1uage the Ohurch ha:s deve1oped oveil.' the centuries. The method of translation employed here has invo1 lved consultation of classical and medieval dictionaries, reference to arguably rep-!l1esentative classical and medieval 1 authors, tracing of the word 'being ioonsidered through t1he documents of Vatican II, con- 'sideration of 1appearance of the word in other Church documents, cross-reference to other uses of the word within Huma,nae Vitae itself, and reference to the Italian" 1 original." 1 l In preparation for this article reference was made to six English translations : (a) the translation done by the NC News Service, made widely available by the Daughters of Saint Paul, Of Human Life (Boston, Mass.: Daughters of St. Paul, 1968), hereafter referred to as the "usual translation" and designated by HY; (b) the translation by the Catholic Truth Society printed in John Horgan, Humanae Vitae and the Bishops (Shannon, Ireland: Irish University Press, 1972), 33-53; this translation was modified and reprinted in (c) The Pope Speaks 13 (1969): 329-346, and in (d) the Vatican Press Office translation, " Encyclical Letter on the Regulation of Births " in Vatican II: More Post-Conciliar Doauments, ed. Austin Flannery, O.P. (Northport, N. Y.: Costello Publishing Company, 1982), 397-416; (e) the translation by Rev. Marc Calegari, S.J., Humanae Vitae (San Francisco: Ignatius Press, 1978), which has undergone a further, as of yet unpublished, revision. 'There is one translation (f) that was made entirely from the Latin, by Rev. A. J. Durand, Humanae Vitae: A New Translation (Bethlehem, Pa.: Catechetical Communications; no date given); it is, though, not widely available. Rev. Calegari, in private communication with this author, noted that the document was originally written in Italian, though the Latin text is the official text. He also stated that the modern language versions were made from the Italian text. My comparisons of the translations of Humanae Vitae with the Italian and the Latin versions indicate that Rev. Calegari is correct in saying that most modern versions are based on the Italian, though a few, most notably that by the Catholic Truth Society, have clearly made reference to the... (shrink)

The ancient theory of substance and accident is supposed to make sense of complex unities in a way that respects both their unity and their complexity. On Hume’s view such complex unities are only fictitiously unities. This result follows from his thoroughgoing critique of the theory of substance. I will characterize the theory Hume is critiquing as it is presented in Locke, presupposing what Bennett calls the “Leibnizian interpretation.” Locke uses the word ‘substance’ in two senses. Call substance in the (...) first sense “individual substance” and in the second sense “pure substance.” I will discuss the seven main parts of Hume’s view: (I) that we have no idea of pure substance, (II) that there is no complex individual substance, except in a loose sense, (III) that the fiction of complex individual substance arises in a way parallel to that of the fiction of identity through time, and (IV) results in the fiction of pure substance, (V) that simple qualities and perceptions satisfy the definition of individual substance, (VI) that there is no such thing as inherence, and (VII) that there is no such thing as pure substance. Hume’s views on substance are often mentioned without being discussed in detail. Kemp Smith, Stroud, and Garrett, for example, mostly summarize various claims of Hume in the course of expounding on his theory of the idea of personal identity. In contrast, I will attempt to present a systematic treatment of Hume on substance as a refutation of Locke. (shrink)