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)

We report specific heat and μSR measurements on Th and/or B substituted UBe13. The specific heat data show that either Th or B substitution reduces the Kondo temperature TK and increases the entropy at the superconducting transition by almost 20%, indicating an enhanced density of states. However, whereas μSR shows clear evidence for magnetic correlations for Th substitutions, no magnetism is observed for B substitutions. The enhanced specific heat jump in the B-substituted material is associated with a change in the (...) superconducting properties as TK is reduced. (shrink)

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)

Well-documented differences in the psychology and behavior of men and women have spurred extensive exploration of gender's role within the brain, particularly regarding emotional processing. While neuroanatomical studies clearly show differences between the sexes, the functional effects of these differences are less understood. Neuroimaging studies have shown inconsistent locations and magnitudes of gender differences in brain hemodynamic responses to emotion. To better understand the neurophysiology of these gender differences, we analyzed recordings of single neuron activity in the human brain as (...) subjects of both genders viewed emotional expressions. This study included recordings of single-neuron activity of 14 (6 male) epileptic patients in four brain areas: amygdala (236 neurons), hippocampus ( n = 270), anterior cingulate cortex ( n = 256), and ventromedial prefrontal cortex ( n = 174). Neural activity was recorded while participants viewed a series of avatar male faces portraying positive, negative or neutral expressions. Significant gender differences were found in the left amygdala, where 23% ( n = 15∕66) of neurons in men were significantly affected by facial emotion, vs. 8% ( n = 6∕76) of neurons in women. A Fisher's exact test comparing the two ratios found a highly significant difference between the two ( p. (shrink)

© 2015, Springer-Verlag Berlin Heidelberg.Genetic studies have identified single nucleotide polymorphisms associated with the risk of prostate cancer. It remains unclear whether such genetic variants are associated with disease aggressiveness. The NCI-SPORE Genetics Working Group retrospectively collected clinicopathologic information and genotype data for 36 SNPs which at the time had been validated to be associated with PC risk from 25,674 cases with PC. Cases were grouped according to race, Gleason score and aggressiveness. Statistical analyses were used to compare the frequency (...) of the SNPs between different disease cohorts. After adjusting for multiple testing, only PC-risk SNP rs2735839 was significantly and inversely associated with aggressive and high-grade disease in European men. Similar associations with aggressive and high-grade disease were documented in African-American subjects. The G allele of rs2735839 was associated with disease aggressiveness even at low PSA levels in both European and African-American men. Our results provide further support that a PC-risk SNP rs2735839 near the KLK3 gene on chromosome 19q13 may be associated with aggressive and high-grade PC. Future prospectively designed, case-case GWAS are needed to identify additional SNPs associated with PC aggressiveness. (shrink)

The body-oriented approach in the philosophy of cognitive sciences is gaining in importance in the conditions of the formation of new high-tech contexts. The problem of interoception and integration of bodily data into socio-economic processes requires a comprehensive analysis and ethical assessment. This article examines the conceptual foundations of the body-oriented approach and its impact on the essence of cognitive processes. The main advantages and disadvantages of this approach are presented. We consider the methodological conflict zones of the bodily paradigm (...) and traditional methodological attitudes of the cognitive sciences. The system ofinteroceptive sensations is a special «layer» of bodily experience. The social functions of interoceptive sensations are an interdisciplinary research area that focuses on the mechanisms of interaction between the private content of bodily experience and systems of social interaction. The regularity between interoceptive sensations and human behavioral patterns reflects the importance of examining bodily data. Today, the market for bodily data is just beginning to form, but at the same time it is already playing an important role in global digital transformation processes. A multitude of applications and wearable digital devices that track bodily activity and generate gigantic amounts of data are used today by millions of people around the world. The identification of bodily activity leads to the emergence of new forms of interaction between a person and socio-institutional systems, the specific properties of which are also considered in this article. (shrink)

The theory of mental models and its computer implementations have led to crucial experiments showing that no standard logic—the sentential calculus and all logics that include it—can underlie human reasoning. The theory replaces the logical concept of validity (the conclusion is true in all cases in which the premises are true) with necessity (conclusions describe no more than possibilities to which the premises refer). Many inferences are both necessary and valid. But experiments show that individuals make necessary inferences that are (...) invalid, e.g., Few people ate steak or sole; therefore, few people ate steak. Other crucial experiments show that individuals reject inferences that are not necessary but valid, e.g., He had the anesthetic or felt pain, but not both; therefore, he had the anesthetic or felt pain, or both. Nothing in logic can justify the rejection of a valid inference: a denial of its conclusion is inconsistent with its premises, and inconsistencies yield valid inferences of any conclusions whatsoever including the one denied. So inconsistencies are catastrophic in logic. In contrast, the model theory treats all inferences as defeasible (nonmonotonic), and inconsistencies have the null model, which yields only the null model in conjunction with any other premises. So inconsistences are local. Which allows truth values in natural languages to be much richer than those that occur in the semantics of standard logics; and individuals verify assertions on the basis of both facts and possibilities that did not occur. (shrink)

This collection of philosophical studies is dedicated to Prof. Buytendijk on the occasion of his retiring from the chair of philosophy at the University of Utrecht. The importance of the publication far surpasses the mere fact of honouring an outstanding scholar. For Buytendijk has indeed been one of the most active pioneers in the working out of a new approach to problems in the field of psychology and has been, together with other collaborators, instrumental in elaborating a new ’style’ as (...) it were in psychology. The sub-title of the present work speaks about ’psychologie humaine’. This adjective does not so much qualify the object of these contributions as their general spirit. As a reaction against the experimental psychology widely practised and taught at the beginning of the century, a psychology whose method was modelled very closely on that of the physical sciences, a new conception of psychology was developed. The central idea was this: nothing of real interest can be said and no real contribution to progress in the field of psychology can be made, as long as the primary and proper purpose and function of psychology as a science is forgotten, namely the understanding of man. Buytendijk was one of the first to stress how very important it is for psychology not to overlook this absolutely basic idea. One of the central notions, therefore, in his work is the notion of “encounter”. This notion emphasizes the fact that the psychologist has not only to measure and to describe a certain object, but must also of necessity endeavour to meet or ’encounter’ man himself, that is, a subject that acts in a purposeful way. And precisely in this Buytendijk’s work can be seen to belong to the so-called ’phenomenological’ school. (shrink)

We resolve the two problems that Hardman raises. The first problem arises from a misunderstanding: the crucial distinction is between one-model and multiple-model problems. The second problem illuminates a deeper principle: conclusions depend on the procedures for interpreting models. We describe an algorithm that obviates the problem and empirical work that reveals a new view of syllogistic reasoning.

Some people have supposed that utility is good in itself, non-in-strumentally good, as distinct from good because conducive to other good things. And in modern versions of this view, utility often means want-satisfaction, as distinct from pleasure or happiness. For your want that p to be satisfied, is it necessary that you know or believe that p, or sufficient merely that p is true? However that question is answered, there are problems with the view that want-satisfaction is a non-instrumental good. (...) What if you want something only because you have a false belief? What if the time at which you want that p is fifty or five hundred years before the time to which p itself refers? To meet these difficulties, qualifications have to be introduced, and much has been written about how exactly these qualifications are to be framed.1 There is however what may be a rather more serious objection to the view that want-satisfaction is a non-instrumental good, or rather to the combination of that view with the principle that it is sufficient for your want that p to be satisfied simply that p is true. The objection is that this combination forces you to give undue weight to the mere acquisition of desires when you come to make judgements about changes in the value of things. It forces you to say that for any true proposition p, which initially you do not want to be true, your mere acquisition of a desire that p will, other things being equal, make the world better. Non-instrumental value can be increased merely by multiplying desires, even though everything else remains the same. Surely, however, improving the world is not as easy as that. (shrink)

Van der Henst argues that the theory of mental models lacks a pragmatic component. He fills the gap with the notion that reasoners draw the most relevant conclusions. We agree, but argue that theories need an element of “nondeterminism.” It is often impossible to predict either what will be most relevant or which particular conclusion an individual will draw.

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)

The diverse essays in Joseph Cropsey’s Political Philosophy and the Issues of Politics are unified by their common theme, the complex relationship between thought and politics. The book’s organization reflects its theme, moving from politics to thought. The essays of the first three sections of the book reformulate the way we view ourselves and the political-moral issues confronting us, at the same time that they strengthen our moral resources in the face of our regime’s tendency to weaken them. For example, (...) Cropsey counters the gross hedonism implied in the desire to overcome alienation when he recommends that justice replace alienation as a dominant term in political discourse. Although our regime was originally organized to function without relying on virtue to produce public advantage, Cropsey includes moral virtue, along with legality and raison d’etat, in the elements upon which statesmanship draws. The third section of the book culminates in a critique of the acquisitive egoism of capitalism from the perspective of magnanimity rather than from that of brotherly love. The former perspective favors "the moral fortitude of the individual [and] the community". Cropsey asks, however, "[i]s it possible for a nation simply to adopt the moral principle of its choice?" or do its laws and customs, its defining documents, not imply a morality? Cropsey’s most extensive treatment of the relationship between what constitutes a nation and its capacity for growth through the activity of thought is found in his introductory essay on the American regime. There he shows how a people’s national identity is modified by clarifications and interpretations of a nation’s constitutive documents. The power of thought, however, is not without limit, for the original constitution acts upon its critiques so as to assimilate them to its own moral tendencies. (shrink)

In this study, we examined moral issues and gender differences in ethical judgment using Reidenbach and Robin’s [Journal of Business Ethics9 (1990) 639) multidimensional ethics scale (MES). A total of 340 undergraduate students were asked to provide ethical judgment by rating three moral issues in the MES labeled: ‚sales’, ‚auto’, and ‚retail’ using three ethics theories: moral equity, relativism, and contractualism. We found that female students’ ratings of ethical judgment were consistently higher than that of male students across two out (...) of three moral issues examined (i.e., sales and retails) and ethics theories; providing support for Eagly’s [1987, Sex Differences in Social Behavior: A Social-role Interpretation. (Lawrence Erlbaum Associates, Inc, Hillsdale, NJ, England)] social role theory. After controlling for moral issues, women’s higher ratings of ethical judgment over men’s became statistically non-significant. Theoretical and practical implications based on the study’s findings are provided. (shrink)

Background: Emergency exception to informed consent regulation was introduced to provide a venue to perform research on subjects in emergency situations before obtaining informed consent. For a study to proceed, institutional review boards need to determine if the regulations have been met.Aim: To determine IRB members’ experience reviewing research protocols using emergency exception to informed consent.Methods: This qualitative research used semistructured telephone interviews of 10 selected IRB members from around the US in the fall of 2003. IRB members were chosen (...) as little is known about their views of exception to consent, and part of their mandate is the protection of human subjects in research. Interview questions focused on the length of review process, ethical and legal considerations, training provided to IRB members on the regulations, and experience using community consultation and notification. Content analysis was performed on the transcripts of interviews. To ensure validity, data analysis was performed by individuals with varying backgrounds: three emergency physicians, an IRB member and a layperson.Results: Respondents noted that: emergency exception to informed consent studies require lengthy review; community consultation and notification regulations are vague and hard to implement; current regulations, if applied correctly, protect human subjects; legal counsel is an important aspect of reviewing exception to informed-consent protocols; and IRB members have had little or no formal training in these regulations, but are able to access materials needed to review such protocols.Conclusions: This preliminary study suggests that IRB members find emergency exception to informed consent studies take longer to review than other protocols, and that community consultation and community notification are the most difficult aspect of the regulations with which to comply but that they adequately protect human subjects. (shrink)

The aim of this paper is to show that the definition of a possible world in the actualist tradition of A. Plantinga, R.M. Adams, R. Chisholm, J. Pollock and N. Wolterstorff is unable to accomodate tensed states of affairs. An example of a tensed state of affairs is the transiently obtaining state of affairs that the storm is present, which obtains only if its negation, it is not the case that the storm is present also obtains but at different times. (...) A possible world that includes tensed states of affairs and their negations cannot be defined in the traditional way, which states that a possible world is a state of affairs S that includes every state of affairs S' or (exclusive disjunction) the negation of S'. Rather, it must be defined in a new way: A possible world is a state of affairs S that includes every state of affairs S' or (inclusive disjunction) the negation of S', such that for every pair P of mutually contradictory tensed states of affairs entailed by S, the members of P obtain nonsimultaneously in S. (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.

Physicists regularly invoke universal laws, such as those of motion and electromagnetism, to explain events. Biological and medical scientists have no such laws. How then do they acquire a reliable body of knowledge about biological organisms and human disease? One way is by repeatedly returning to, manipulating, observing, interpreting, and reinterpreting certain subjects—such as flies, mice, worms, or microbes—or, as they are known in biology, “model systems.” Across the natural and social sciences, other disciplinary fields have developed canonical examples that (...) have played a role comparable to that of biology’s model systems, serving not only as points of reference and illustrations of general principles or values but also as sites of continued investigation and reinterpretation. The essays in this collection assess the scope and function of model objects in domains as diverse as biology, geology, and history, attending to differences between fields as well as to epistemological commonalities. Contributors examine the role of the fruit fly Drosophila and nematode worms in biology, troops of baboons in primatology, box and digital simulations of the movement of the earth’s crust in geology, and meteorological models in climatology. They analyze the intensive study of the prisoner’s dilemma in game theory, ritual in anthropology, the individual case in psychoanalytic research, and Athenian democracy in political theory. The contributors illuminate the processes through which particular organisms, cases, materials, or narratives become foundational to their fields, and they examine how these foundational exemplars—from the fruit fly to Freud’s Dora—shape the knowledge produced within their disciplines. Contributors Rachel A. Ankeny Angela N. H. Creager Amy Dahan Dalmedico John Forrester Clifford Geertz Carlo Ginzburg E. Jane Albert Hubbard Elizabeth Lunbeck Mary S. Morgan Josiah Ober Naomi Oreskes Susan Sperling Marcel Weber M. Norton Wise. (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)