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)

In ‘Wittgenstein on Language and Rules’, Professor N. Malcolm took us to task for misinterpreting Wittgenstein's arguments on the relationship between the concept of following a rule and the concept of community agreement on what counts as following a given rule. Not that we denied that there are any grammatical connections between these concepts. On the contrary, we emphasized that a rule and an act in accord with it make contact in language. Moreover we argued that agreement in judgments and (...) in definitions is indeed necessary for a shared language. But we denied that the concept of a language is so tightly interwoven with the concept of a community of speakers as to preclude its applicabilty to someone whose use of signs is not shared by others. Malcolm holds that ‘This is an unwitting reduction of Wittgenstein's originality. That human agreement is necessary for “shared” language is not so striking a thought as that it is essential for language simpliciter .’ Though less striking, we believe that it has the merit of being a true thought. We shall once more try to show both that it is correct, and that it is a correct account of Wittgenstein's arguments. (shrink)

Little research has explored the perceptions of military medical providers in the deployed environment and how their perceptions may change over time across an extended military conflict. To our knowledge, no studies have examined military medical providers’ opinions on readiness for their roles in the post-9/11 contingency operations. What has been published indicates that, during the height of Operation Iraqi Freedom, military medical providers often deployed with little notice and minimal formal training. The present report examines data obtained from multiple (...) cohorts of military medical providers (N = 321) deployed to Iraq between 2005 and 2009. Despite varying degrees of support from the U.S. public, our findings indicate that U.S. Air Force military medical providers’ support for the people of Iraq, their belief in the mission, and their ability to influence change did not vary with time. (shrink)

RÉSUMÉ: Cet article examine les conséquences pour l’inégalité sexuelle au Canada des coupures gouvernementales dans les soins de santé et les services sociaux, et les évalue à l’aune de la jurisprudence relative à la Charte. L’auteure soutient que ce recul a en fait désavantagé les femmes d’une manière disproportionnée, et qu’on pourrait y voir, du point de vue de la Charte, une discrimination à leur endroit. Or les gouvernements n’ont offert aucune justification de ces effets discriminatoires qui satisferait aux critères (...) de la Charte en en montrant le caractère raisonnable dans une société libre et démocratique. Présenter l’action gouvernementale comme un exercice neutre de transfert de responsabilités vers les familles et les communautés ne saurait constituer une telle justification. (shrink)

RésuméCet article examine les conséquences pour l'inégalité sexuelle au Canada des coupures gouvernementales dans les soins de santé et les services sociaux, et les évalue à I'aune de la jurisprudence relative à la Charte. L'auteure soutient que ce recul a en fait désavantagé les femmes d'une manière disproportionnée, et qu'on pourrait y voir, du point de vue de la Charte, une discrimination à leur endroit. Or les gouvernements n'ont offert aucune justification de ces effets discriminatoires qui satisferait aux critères de (...) la Charte en en montrant le caractère raisonnable dans une société libre et démocratique. Présenter l'action gouvernementale comme un exercice neutre de transfert de responsabilités vers les families et les communautés ne saurait constituer une telle justification. (shrink)

BackgroundThe ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines are widely endorsed but compliance is limited. We sought to determine whether journal-requested completion of an ARRIVE checklist improves full compliance with the guidelines.MethodsIn a randomised controlled trial, manuscripts reporting in vivo animal research submitted to PLOS ONE (March–June 2015) were randomly allocated to either requested completion of an ARRIVE checklist or current standard practice. Authors, academic editors, and peer reviewers were blinded to group allocation. Trained reviewers performed outcome adjudication (...) in duplicate by assessing manuscripts against an operationalised version of the ARRIVE guidelines that consists 108 items. Our primary outcome was the between-group differences in the proportion of manuscripts meeting all ARRIVE guideline checklist subitems.ResultsWe randomised 1689 manuscripts (control: n = 844, intervention: n = 845), of which 1269 were sent for peer review and 762 (control: n = 340; intervention: n = 332) accepted for publication. No manuscript in either group achieved full compliance with the ARRIVE checklist. Details of animal husbandry (ARRIVE subitem 9b) was the only subitem to show improvements in reporting, with the proportion of compliant manuscripts rising from 52.1 to 74.1% (X2 = 34.0, df = 1, p = 2.1 × 10−7) in the control and intervention groups, respectively.ConclusionsThese results suggest that altering the editorial process to include requests for a completed ARRIVE checklist is not enough to improve compliance with the ARRIVE guidelines. Other approaches, such as more stringent editorial policies or a targeted approach on key quality items, may promote improvements in reporting. (shrink)

A comprehensive treatment of the concept of causation in evolutionary biology that makes clear its central role in both historical and contemporary debates. Most scientific explanations are causal. This is certainly the case in evolutionary biology, which seeks to explain the diversity of life and the adaptive fit between organisms and their surroundings. The nature of causation in evolutionary biology, however, is contentious. How causation is understood shapes the structure of evolutionary theory, and historical and contemporary debates in evolutionary biology (...) have revolved around the nature of causation. Despite its centrality, and differing views on the subject, the major conceptual issues regarding the nature of causation in evolutionary biology are rarely addressed. This volume fills the gap, bringing together biologists and philosophers to offer a comprehensive, interdisciplinary treatment of evolutionary causation. Contributors first address biological motivations for rethinking evolutionary causation, considering the ways in which development, extra-genetic inheritance, and niche construction challenge notions of cause and process in evolution, and describing how alternative representations of evolutionary causation can shed light on a range of evolutionary problems. Contributors then analyze evolutionary causation from a philosophical perspective, considering such topics as causal entanglement, the commingling of organism and environment, and the relationship between causation and information. Contributors John A. Baker, Lynn Chiu, David I. Dayan, Renée A. Duckworth, Marcus W Feldman, Susan A. Foster, Melissa A. Graham, Heikki Helanterä, Kevin N. Laland, Armin P. Moczek, John Odling-Smee, Jun Otsuka, Massimo Pigliucci, Arnaud Pocheville, Arlin Stoltzfus, Karola Stotz, Sonia E. Sultan, Christoph Thies, Tobias Uller, Denis M. Walsh, Richard A. Watson. (shrink)

The article looks into the issues, outlined in M. Baker's The Atoms of Language: The Mind's Hidden Rules of Grammar. This work is notable for the parametric theory of the languages, set out in it, according to which languages are different, nevertheless retaining the ability to be compared. That can be further supported by the assertion that the differences among languages are determined by "a smallish number of discreet elements, called parameters."What is more, the diversity of language reveals a (...) certain regularity, very much resembling that of Mendeleev's periodic table of chemical elements. Our research team of professional linguists and philosophers put this claim to a critical analysis, the results of which are featured in this article. One of the major ones among them is the supposition that Baker, in accordance with the traditions of Chomsky generative linguistics, turns temporal continuums into special relations. He did that without discussing the consequences of such move, which made it impossible to develop the psychological and linguistic aspect of the subject raised by him. (shrink)

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)

Context: Immunity includes cognitive concepts: the organism is thought to specifically recognize foreign materials and develop a memory of these encounters. Vaccines are thought to work by enhancing this immunological memory. Lymphocytes are key cells and specific antibodies are key molecules in immune recognition. Antibodies are blood proteins called “immunoglobulins.” Spontaneously formed immunoglobulins are seen as “natural” antibodies to dietary components and commensal bacteria. Immune cognition is used simply as a didactic metaphor. Problem: Do the cognitive aspects of immunology stem (...) from the activities of cells and molecules, or are they ascribed by the immunologist operating as a human observer? (1) An immense variety of immunoglobulins may bind to the same antigen with different binding energies. It is the immunologist who arbitrates the boundary between those that are specific (and declared antibodies) and those that are not. Specific antibodies serve as functional labels pasted onto natural immunoglobulins, as if they were recognizing elements. Is this “arbitration” the true cognitive event ascribed to immunoglobulins and lymphocytes? (2) A major impasse exists between progress in experimental immunology and its translation into clinical results. A proper understanding of immunological activity demands a wider view of an organism’s biology and, also, of the interference of human observers in delineating experimental realities, such as the specificity of immune recognition. Maturana’s biology of cognition and language provides one such approach. Method: Use of Maturana’s biology of cognition and language concepts to describe immunological activity. Results: A whole new understanding of immunological activity is suggested. Implications: A major change in the way of seeing is proposed that may eventually help the translation of this knowledge into clinical results. Furthermore, the immune system may also become a proper model for cognitive analyses. (shrink)

The ‘multicultural clinical interaction’ presents itself as a dilemma for the mental health practitioner. Literature describes two problematic areas where this issues emerges - how to make an adequate distinction between religious rituals and the rituals that may be symptomatic of ‘obsessive compulsive disorder’ (OCD), and how to differentiate ‘normative’ religious or spiritual beliefs, behaviours, and experiences from ‘psychotic’ illnesses. When it comes to understanding service user’s ‘idioms of distress’, beliefs about how culture influences behaviour can create considerable confusion and (...) ‘normative uncertainty’ for mental health practitioners. In the absence of clear diagnostic and assessment criteria on distinguishing between ‘culture’ and ‘psychopathology’, practitioners have had to rely on their own intuition and seek out possible ‘strategies’ or ‘procedures’ from a contradictory and cross-disciplinary evidence base. Decontextualisation of service users’ experiences may result in the pathologisation of culturally ‘normative’ phenomenon, ‘category fallacy’ errors, and poor health care experiences and outcomes for service users. This paper situates this dilemma within a wider debate that has concerned both the biomedical and social sciences, namely, the unresolved question of ‘normality’ or ‘abnormality’. Indeed, issues that arise from dilemmas surrounding the question of ‘culture’ or ‘psychopathology’ are intimately tied to wider cultural ideas about what is considered ‘normal’. The disciplines of psychiatry, psychology, and medical anthropology have struggled to establish workable criteria against which to judge behaviour as ‘normal’, ‘abnormal’, or ‘pathological’. Three models for understanding mental ‘abnormality’ are evident in ‘transcultural psychiatry’ (what is now commonly known as ‘cultural psychiatry’), and these models have corresponded closely to the interpretive models used by anthropologists attempting to make sense of the apparent diversity of human societies. The three models of ‘absolutism’, ‘universalism’ and ‘cultural relativism’ have not only important consequences for the nature and conduct of research enquiry, but also have implications for how the dilemma of ‘culture’ or ‘psychopathology’ is attended to in clinical practice. (shrink)

Background:New graduate transition into the workforce is challenging and can involve managing ethical tensions. Ethical tensions cause new graduates to doubt their capabilities due to their lack of experience. To support new graduates, we need to know what these ethical tensions are.Objectives:To explore the ethical tensions perceived to occur in practice for new graduate health professionals.Research design:This qualitative systematic review involved a search of five databases (Medline, EMBASE, AMED, CINAHL and Scopus) which resulted in the retrieval of 3554 papers. After (...) the two-phased screening process, eight studies were identified that met the inclusion criteria and had rich data on the review question. Articles were read several times, critically appraised and analysed through thematic analysis.Ethical considerations:No ethical approval was required for the systematic review. The review was conducted following well-established reporting guidelines enabling transparency and rigour.Findings:Studies originated from Australia, United States, Iran and China. One study included speech pathologists and seven were with nurses. Four themes included the following: (1) enduring an unknown workplace culture that generates uncertainty without support for new graduates; (2) being vulnerable because of distress from bullying, exclusion and being a scapegoat; (3) constraining systems and institutional restrictions that cause dilemmas; and (4) experiencing disillusionment from lost ideals about ethical practice.Discussion:This review has brought to light the vulnerability of new graduates to negative workplace culture and collegial incivility. In addition, new graduates are subjected to ethical tensions created by institutional constraints which can create dilemmas and uncertainties through practice that does not align with what they anticipated.Conclusion:Understanding ethical tensions experienced by new graduates enables provision of informed support. There needs to be considerable cultural change for orientation and socialisation of new graduates to enable them to learn and manage ethical tensions. (shrink)

Summary Tycho Brahe's lunar theory, mostly the work of his assistant Christian Longomontanus, published in the Progymnasmata (1602), was the most advanced and accurate lunar theory yet developed. Its principal innovations are: the introduction of equant motion for the first inequality in order to separate the determination of direction and distance; a more accurate limit for the second inequality although requiring a more complex calculation; additional inequalities of the variation and, in place of the annual inequality in Tycho's earlier theory, (...) a reduction in the equation of time; in the latitude theory a variation of the inclination of the orbital plane and an inequality of the motion of the nodes; a reduction in the range of variation of distance, parallax, and apparent diameter. Some of these were already present in Tycho's earlier lunar theory (1599), but all were changed in notable ways. Twenty years later Longomontanus published a modified version of the lunar theory in Astronomia Danica (1622), for the purpose of facilitating the calculation through new correction tables, and also explained his reasons for parts of the theory in the Progymnasmata. This paper is a technical study of both lunar theories. (shrink)

Collaborative remembering is essential to enabling teams to build shared understanding of projects and their progress. This article presents an analysis of collaborative remembering sequences in a corpus of interactions collected in a workplace where a team of designers developed a video television commercial. On the basis of coding and analysing linguistic and bodily behaviors in 158 such sequences, extracted from over 45 hours of video recordings, recurrent patterns of collaborative remembering processes were identified, relating to the interplay of work (...) roles. This article shows that collaborative remembering in the design studio is structured by behavioural, interactive and social factors. (shrink)

Robert Grosseteste was a prolific theological and scientific writer, a translator, bishop of Lincoln , and a candidate for sainthood. There have been several studies of his life and his works, the most recent being that of Richard Southern. Nevertheless, James McEvoy's comment in 1983 that “the course of Grosseteste's life up until 1225 is almost completely unknown” remains largely true. The problem is common in medieval history—there is a dearth of reliable sources for the subject's early life. I do (...) not intend to discuss here Grosseteste's youth, or even his life until 1198 . I will accept, with a few reservations, the model Southern presented for Grosseteste's life until 1198 — that Grosseteste came from an undistinguished family, acquired an education, and may have taught in local schools; after serving the bishop of Lincoln in a minor capacity, he managed to obtain an administrative position under Bishop de Vere in the diocese of Hereford. Unfortunately, Bishop de Vere died on Christmas Day 1198, and his household was disbanded. It is the period following 1198 until 1225 that needs scrutiny. The recent discovery of a reference to Robert Grosseteste in a thirteenth-century cartulary demands that we reconsider the way in which historians have structured Grosseteste's career, both because of what this manuscript records and because of the light it sheds upon the methodology that has underpinned Grosseteste scholarship. (shrink)

Upshot: According to Biology of Cognition and Language (Maturana’s approach) the immune system is not a cognitive system and defining of a cognitive paradigm is not what we understand as a Maturanian approach to immunology. The true cognitive actions in immunology are performed by immunologists acting as observers, not by body organs or systems. Stimuli and responses are not adequate concepts in the description of systems. As a closed network of cellular/molecular interactions, the immune system yields patterns of activity as (...) is transparent in robust conserved profiles of reactivity of natural immunoglobulins, as investigated by Nóbrega et al. and Cohen et al., which offer the opportunity to unravel its natural, spontaneous activity. Dietary materials, products of the commensal microbiome are the most abundant and common elements continuously incorporated to the network activity and, thus, also represent an important avenue of investigation. (shrink)