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)

Theorists have oversold the usefulness of predicate logic and generative grammar to the study of language origins. They have searched for models that correspond to semantic properties, such as truth, when what is needed is an empirically testable model of evolution. Such a model is required if we are to explain the origins of linguistic properties by appealing to general properties of linguistic engendering, rather than to the advent of genotypes with the propensity to produce certain brain mechanisms. While the (...) latter sort of explanation has a place, no theory can be considered an `evolutionary' theory without the former. We introduce a general notion of engendering, whose primary virtue is its freedom from assumptions regarding the nature of colloquial change. We use it to frame a conjecture about the evolution of centre embedded clauses; one which makes the fewest possible assumptions about the neural requirements upon individual brains. Keywords: biology of language; epigenesis; engendering; evolution; mutation; population; recursion. (shrink)

This discussion paper considers how seldom recognised theories influence clinical ethics committees. A companion paper examined four major theories in social science: positivism, interpretivism, critical theory and functionalism, which can encourage legalistic ethics theories or practical living bioethics, which aims for theory–practice congruence. This paper develops the legalistic or living bioethics themes by relating the four theories to clinical ethics committee members’ reported aims and practices and approaches towards efficiency, power, intimidation, justice, equality and children’s interests and rights. Different approaches (...) to framing ethical questions are also considered. Being aware of the four theories’ influence can help when seeking to understand and possibly change clinical ethics committee routines. The paper is not a research report but is informed by a recent study in two London paediatric cardiac units. Forty-five practitioners and related experts were interviewed, including eight members of ethics committees, about the work of informing, preparing and supporting families during the extended process of consent to children’s elective heart surgery. The mosaic of multidisciplinary teamwork is reported in a series of papers about each profession, including this one on bioethics and law and clinical ethics committees’ influence on clinical practice. The qualitative social research was funded by the British Heart Foundation, in order that more may be known about the perioperative views and needs of all concerned. Questions included how disputes can be avoided, how high ethical standards and respectful cooperation between staff and families can be encouraged, and how minors’ consent or refusal may be respected, with the support of clinical ethics committees. (shrink)

The corporatization of U.S. health care has directed cost containment efforts toward scrutinizing the clinical decisions of physicians. This stimulated a variety of new utilization management interventions, particularly in hospital and managed care settings. Recent changes in fee-for-service medicine and physicians' traditional agency relationships with patients, purchasers, and insurers are examined here. New information systems monitoring of physician ordering behavior has already begun to impact on physician autonomy and the relationship of physicians to provider organizations in both for-profit and not-for-profit (...) sectors. As managed care practice settings proliferate, serious ethical questions will be raised about agency relationships with patients.This article examines health system dynamics altering the historical agency relationship between the physician and patient and eroding the traditional autonomy of the medical profession in the United States. The corporatization of medicine and the accompanying information systems monitoring of physician productivity is seen to account of such change, now posing serious ethical dilemmas. (shrink)

Responsible data management is a multifaceted topic involving standards within the research community regarding research design and the sharing of data as well as the collection, selection, analysis and interpretation of data. Transparency in the manipulation of images is increasingly important in order to avoid misrepresentation of research findings, and research oversight is also critical in helping to assure the integrity of the research process. Intellectual property issues both unite and divide academe and industry in their approaches to data management. (...) Central to the realization and promulgation of responsible data management is clear and careful communication of standards and expectations within the research community to trainees as well as among colleagues. These topics are examined and explored in depth in a special issue of Science and Engineering Ethics on responsible data management. (shrink)

Functionalism offers an account of the relations that hold between behavioural functions, information and neural processing, and conscious experience from which one can draw two inferences: for any discriminable difference between qualia there must be an equivalent discriminable difference in function; and for any discriminable functional difference within a behavioural domain associated with qualia, there must be a discriminable difference between qualia. The phenomenon of coloured hearing synaesthesia appears to contradict the second of these inferences. We report data showing that (...) this form of synaesthesia is genuine and probably results from an aberrant projection from cortical language areas to a region specialized for the perception of colour. Since functionalism purports to be a general account of consciousness, one such negative instance, if it can be further sustained empirically, is sufficient to invalidate it. (shrink)

In The Stigma of Genius: Einstein, Consciousness and Critical Education, we muse over ways in which to be, to become, to recognize uniqueness and different paths to genius. Understanding that there is no prescribed procedure, but only multiple actions, means, measures in which to recognize or teach to genius, we look at Einstein's life and knowledges to connect our pedagogies and students. Today's schools often exemplify an inability to stimulate and encourage students to find passion, goals, and reasons to be (...) educated. Our public school students are often not succeeding, many are failing and are discouraged. Teachers are exhausted, overworked, lacking respect and administrative support in districts controlled by local and national politics. Using Einstein as an example, but also a metaphor for educators, The Stigma of Genius is straight talk about the needs for schools/teachers/administrators/students to become critically and contextually aware. We argue for an education which is conscious of students' needs, and the nuances within each school and each classroom. Discussing cognition, classes, urban education, and diversity, we have attempted to circle back to Einstein and understand ways to support and encourage today's geniuses. (shrink)

The neuromuscular junction has been used for several decades as an excellent model system to examine the cellular and molecular events involved in the formation and maintenance of a differentiated chemical synapse. In this context, several laboratories have focused their efforts over the last 15 years on the important contribution of transcriptional mechanisms to the regulation of the development and plasticity of the postsynaptic apparatus in muscle fibers. Converging lines of evidence now indicate that post‐transcriptional events, operating at the level (...) of mRNA stability and targeting, are likely to also play key roles at the neuromuscular junction. Here, we present the recent findings highlighting the role of these additional molecular events and extend our review to include data showing that post‐transcriptional events are also important in the control of the expression of genes encoding synaptic proteins in muscle cells placed under different conditions. Finally, we discuss the possibility that mis‐regulation of post‐transcriptional events can occur in certain neuromuscular diseases and cause abnormalities of the neuromuscular junction. BioEssays 25:25–31, 2003. © 2002 Wiley Periodicals, Inc. (shrink)

Many believe that the ethical problems of donation after cardiocirculatory death (DCD) have been "worked out" and that it is unclear why DCD should be resisted. In this paper we will argue that DCD donors may not yet be dead, and therefore that organ donation during DCD may violate the dead donor rule. We first present a description of the process of DCD and the standard ethical rationale for the practice. We then present our concerns with DCD, including the following: (...) irreversibility of absent circulation has not occurred and the many attempts to claim it has have all failed; conflicts of interest at all steps in the DCD process, including the decision to withdraw life support before DCD, are simply unavoidable; potentially harmful premortem interventions to preserve organ utility are not justifiable, even with the help of the principle of double effect; claims that DCD conforms with the intent of the law and current accepted medical standards are misleading and inaccurate; and consensus statements by respected medical groups do not change these arguments due to their low quality including being plagued by conflict of interest. Moreover, some arguments in favor of DCD, while likely true, are "straw-man arguments," such as the great benefit of organ donation. The truth is that honesty and trustworthiness require that we face these problems instead of avoiding them. We believe that DCD is not ethically allowable because it abandons the dead donor rule, has unavoidable conflicts of interests, and implements premortem interventions which can hasten death. These important points have not been, but need to be fully disclosed to the public and incorporated into fully informed consent. These are tall orders, and require open public debate. Until this debate occurs, we call for a moratorium on the practice of DCD. (shrink)

Nursing has a unique opportunity to address issues of structural violence that contribute to poor health outcomes. Models for designing nursing care relative to the social determinants of health can be adapted from the discipline of peace studies and the phenomenon of peacebuilding. The aim of this qualitative study was to describe the lived experience of peacebuilding from the perspective of community or public health nurses. Interviews were conducted with eight participants. Attributes of the peacebuilder included fostering human relationships that (...) value the inherent worth and dignity of others, nurturing a character of humility and moral courage, and contemplating the personal cost of engaging in prolonged processes of peacebuilding. Practices of peacebuilding included mediating conflict through multilayered processes, accompanying others to places of empowerment, and utilizing interdisciplinary teaching and learning to build capacity for change. Increasing an understanding of the lived experience of peacebuilding by nurses is relevant to nursing research, theory, and practice, and adds to a broader understanding of peacebuilding. (shrink)

In order to make strategic decisions and improve their firm’s performance, top management teams must have information on the competitive context in general, and the firm’s competitors in particular. During the decision-making process, top managers can have access to “privileged information”—i.e., information of a confidential and potentially strategic nature that could ultimately confer a decisional advantage over competing parties. However, obtaining and using privileged information in a business context is often illegal—and if not, is usually deemed unethical or “against the (...) rules.” Using a quasi-experimental design, this study explores the reasons why an individual might engage in such unethical behavior. We assess the extent to which managers use privileged information with respect to perceived team cohesion and peers’ ethicality. More specifically, our results show that the use of privileged information is predicted by the decision-maker’s perceptions of their team cohesion and their peers’ ethicality. Moreover, we find that team performance, as a group-level nonself-reported factor, moderates the relationship between cohesion and the use of privileged information. The relationship between cohesion, ethical behavior, and team performance is also discussed. We draw on these findings to make some practical suggestions on how to incorporate practices that could better prevent the unethical use of privileged information in strategic decision-making processes. (shrink)

Ageing causes progressive decline in metabolic, behavioural, and physiological functions, leading to a reduced health span. The extracellular matrix (ECM) is the three‐dimensional network of macromolecules that provides our tissues with structure and biomechanical resilience. Imbalance between damage and repair/regeneration causes the ECM to undergo structural deterioration with age, contributing to age‐associated pathology. The ECM ‘Ageing Across the Life Course’ interdisciplinary research network (ECMage) was established to bring together researchers in the United Kingdom, and internationally, working on the emerging field (...) of ECM ageing. Here we report on a consultation at a joint meeting of ECMage and the Medical Research Council / Versus Arthritis Centre for Integrated Research into Musculoskeletal Ageing, held in January 2023, in which delegates analysed the key questions and research opportunities in the field of ECM ageing. We examine fundamental biological questions, enabling technologies, systems of study and emerging in vitro and in silico models, alongside consideration of the broader challenges facing the field. (shrink)

Non‐invasive microanalytical methods have been devised to study the energy metabolism of single human preimplantation embryos. Psyruvate, which is added routinely to all media used to culture human embryos, is consumed throughout the preimplantation period, with glucose assuming an increasing role at embryo compaction and blastocyst formation. All of the glucose consumed may be accounted for by the appearance of lactate in the incubation medium. The enzyme hexokinase my be involved in regulating this aerobic glycolysis. There is cosiderable indirect evidence (...) for the utilisation of endogenous as opposed to exogenous energy substrates, the most likely candidate being protein. Information on early human embryo metabolismis likely to find application in a number of areas: these include the improvement of techniques for assisted human conception, notably in the selection of embryos for transfer following In Vitro Fertilisation; the diagnosis of gentic defects at the preimplantation stage; increased undersding of the causes of implantation failure and miscarriage, and the development of novel post‐coital contraceptives. (shrink)

Background This analysis is about practical living bioethics and how law, ethics and sociology understand and respect children’s consent to, or refusal of, elective heart surgery. Analysis of underlying theories and influences will contrast legalistic bioethics with living bioethics. In-depth philosophical analysis compares social science traditions of positivism, interpretivism, critical theory and functionalism and applies them to bioethics and childhood, to examine how living bioethics may be encouraged or discouraged. Illustrative examples are drawn from research interviews and observations in two (...) London paediatric cardiac units. This paper is one of a series on how the multidisciplinary cardiac team members all contribute to the complex mosaic of care when preparing and supporting families’ informed consent to surgery. Results The living bioethics of justice, care and respect for children and their consent depends on theories and practices, contexts and relationships. These can all be undermined by unseen influences: the history of adult-centric ethics; developmental psychology theories; legal and financial pressures that require consent to be defined as an adult contract; management systems and daily routines in healthcare that can intimidate families and staff; social inequalities. Mainstream theories in the clinical ethics literature markedly differ from the living bioethics in clinical practices. Conclusion We aim to contribute to raising standards of respectful paediatric bioethics and to showing the relevance of virtue and feminist ethics, childhood studies and children’s rights. (shrink)

After five years of consultation, the Institute of Biology formally organized in early 1950. Its goals were twofold: first, to watch relevant legislation and provide the voice of British biologists on international issues; second, to serve the labor and community needs of British biology in both academic and industrial sectors. Years later the institute expanded to incorporate other roles: consultant accreditation, biology education, degree regulation, and history of biology.This anthology celebrates the institute's fiftieth anniversary. Short papers written by members of (...) the institute's history of biology network focus on particular decades. These are interspersed with brief recollections from select participants in institute activities. Appendixes list institute officers, symposia titles, publications, and details on the organization and events of institute branches.These authors practice history as chronology and fact‐collecting. They ask limited questions of past events. No effort is made to connect institute activities to larger issues. No effort is made to understand why these events took place, what enabled them, or how their character came to be defined. No effort is made to compare what happened here with what happened along similar lines elsewhere in British science, British labor, or the life sciences abroad. No effort is made to justify claims of impact and influence. This book is simply a celebration of activity written for insiders who are celebrating their own achievements. Although they can be proud of their accomplishments, this book fails to offer much meaningful explanation.Edited by Brian J. Ford, this book has two values for analytical historians. First, some reminiscences offer interesting suggestions for future study, such as Sam Berry's tale about proposing a Royal Society of Biology. Second, the simple collecting of facts makes this book useful for reference, though an index would have been helpful. For more than this, historians must look elsewhere. (shrink)

This paper examines Pedro Tabensky's claims that rational human life has a single unifying purpose, and that there is an analogy between the skill of living and that of painting. It examines his arguments for the first claim, in particular the relation between ratio nality and different ways in which a life might be unified. For, in addition to the narrative or artistic unification which Tabensky favours, there is also (for example) the possibility of unifying one's life through the adoption (...) of a so-called monolithic end, such as pleasure (assuming that pleasure is monolithic). The paper also investigates the implications of each of these modes of unification for how we should understand the skill of living. According to the narrative or artistic model, living will indeed be like painting; however, according to the mono lithic-end model, living may be more like business management; and other models may make other analogies salient. All this will make a difference to our attitudes to events within our lives, for example, whether the inevitable disturbances within our lives are to be integrated or, rather, eliminated. S. Afr. J. Philos. Vol.23(4) 2004: 353-364. (shrink)

Peer review is a widely accepted instrument for raising the quality of science. Peer review limits the enormous unstructured influx of information and the sheer amount of dubious data, which in its absence would plunge science into chaos. In particular, peer review offers the benefit of eliminating papers that suffer from poor craftsmanship or methodological shortcomings, especially in the experimental sciences. However, we believe that peer review is not always appropriate for the evaluation of controversial hypothetical science. We argue that (...) the process of peer review can be prone to bias towards ideas that affirm the prior convictions of reviewers and against innovation and radical new ideas. Innovative hypotheses are thus highly vulnerable to being “filtered out” or made to accord with conventional wisdom by the peer review process. Consequently, having introduced peer review, the Elsevier journal Medical Hypotheses may be unable to continue its tradition as a radical journal allowing discussion of improbable or unconventional ideas. Hence we conclude by asking the publisher to consider re-introducing the system of editorial review to Medical Hypotheses. (shrink)

Background This analysis is about practical living bioethics and how law, ethics and sociology understand and respect children’s consent to, or refusal of, elective heart surgery. Analysis of underlying theories and influences will contrast legalistic bioethics with living bioethics. In-depth philosophical analysis compares social science traditions of positivism, interpretivism, critical theory and functionalism and applies them to bioethics and childhood, to examine how living bioethics may be encouraged or discouraged. Illustrative examples are drawn from research interviews and observations in two (...) London paediatric cardiac units. This paper is one of a series on how the multidisciplinary cardiac team members all contribute to the complex mosaic of care when preparing and supporting families’ informed consent to surgery. Results The living bioethics of justice, care and respect for children and their consent depends on theories and practices, contexts and relationships. These can all be undermined by unseen influences: the history of adult-centric ethics; developmental psychology theories; legal and financial pressures that require consent to be defined as an adult contract; management systems and daily routines in healthcare that can intimidate families and staff; social inequalities. Mainstream theories in the clinical ethics literature markedly differ from the living bioethics in clinical practices. Conclusion We aim to contribute to raising standards of respectful paediatric bioethics and to showing the relevance of virtue and feminist ethics, childhood studies and children’s rights. (shrink)

This article presents results from a multidisciplinary research project on the integration and transfer of language knowledge into robots as an empirical paradigm for the study of language development in both humans and humanoid robots. Within the framework of human linguistic and cognitive development, we focus on how three central types of learning interact and co-develop: individual learning about one's own embodiment and the environment, social learning (learning from others), and learning of linguistic capability. Our primary concern is how these (...) capabilities can scaffold each other's development in a continuous feedback cycle as their interactions yield increasingly sophisticated competencies in the agent's capacity to interact with others and manipulate its world. Experimental results are summarized in relation to milestones in human linguistic and cognitive development and show that the mutual scaffolding of social learning, individual learning, and linguistic capabilities creates the context, conditions, and requisites for learning in each domain. Challenges and insights identified as a result of this research program are discussed with regard to possible and actual contributions to cognitive science and language ontogeny. In conclusion, directions for future work are suggested that continue to develop this approach toward an integrated framework for understanding these mutually scaffolding processes as a basis for language development in humans and robots. (shrink)

La question platonicienne est traversée par une énigme qui défie les interprètes depuis les travaux de Léon Robin, qui datent de plus d'un siècle. Platon a-t-il élaboré une doctrine, ou sa pensée est-elle tout entière contenue dans les dialogues? Autrement dit, y a-t-il un enseignement secret de Platon qui n'apparaîtrait pas dans son oeuvre écrite? Le témoignage des doxographes, à commencer par Aristote, laisse entendre que Platon a bien enseigné une doctrine, mais comment expliquer le silence des dialogues? Analysant l'étrange (...) passage du Timée qui s'articule sur la gamme pythagoricienne, J.-J. Duhot, qui a aussi été musicien professionnel, en a décrypté la clef, qui avait échappé aux interprètes : le Même code l'octave, soit le rapport 2, et l'Autre code la quinte, soit le rapport 3/2. Cette clef, indiscutable en elle-même, comme le démontre J.-J. Duhot, permet d'établir la grille de lecture qui éclaire toutes les obscurités du passage. On a donc là une double équivalence, entre métaphysique (Un/Multiple), acoustique (octave et quinte), et mathématiques (construction arithmétique de la gamme). J.-J. Duhot montre que c'est la matrice sur laquelle Platon construit son oeuvre et met en place le postulat de mathématicité du monde, qui sera la base de toute la science moderne, à partir de Galilée. La gamme du Timée offre un modèle mathématique, la division de 2 en produits de facteurs dans un système logarithmique, qui résout (métaphoriquement) les problèmes de l'Un et du Multiple. On voit ainsi apparaître un "cycle éléatique" dans lequel, au fil des dialogues, Parménide, Théétète, Sophiste et Politique, se met en place une véritable doctrine platonicienne. Doctrine secrète qui s'offre au lecteur qui sait en décrypter le code. (shrink)

Since the publication of David Lewis’ Counterfactuals, the standard line on subjunctive conditionals with impossible antecedents (or counterpossibles) has been that they are vacuously true. That is, a conditional of the form ‘If p were the case, q would be the case’ is trivially true whenever the antecedent, p, is impossible. The primary justification is that Lewis’ semantics best approximates the English subjunctive conditional, and that a vacuous treatment of counterpossibles is a consequence of that very elegant theory. Another justification (...) derives from the classical lore than if an impossibility were true, then anything goes. In this paper we defend non-vacuism, the view that counterpossibles are sometimes non-vacuously true and sometimes non-vacuously false. We do so while retaining a Lewisian semantics, which is to say, the approach we favor does not require us to abandon classical logic or a similarity semantics. It does however require us to countenance impossible worlds. An impossible worlds treatment of counterpossibles is suggested (but not defended) by Lewis (Counterfactuals. Blackwell, Oxford, 1973), and developed by Nolan (Notre Dame J Formal Logic 38:325–527, 1997), Kment (Mind 115:261–310, 2006a: Philos Perspect 20:237–302, 2006b), and Vander Laan (In: Jackson F, Priest G (eds) Lewisian themes. Oxford University Press, Oxford, 2004). We follow this tradition, and develop an account of comparative similarity for impossible worlds. (shrink)

In Democracy and the Claims of Nature, the leading thinkers in the fields of environmental, political, and social theory come together to discuss the tensions and sympathies of democratic ideals and environmental values. The prominent contributors reflect upon where we stand in our understanding of the relationship between democracy and the claims of nature. Democracy and the Claims of Nature bridges the gap between the often competing ideals of the two fields, leading to a greater understanding of each for the (...) other. (shrink)