This study examined how vocabulary, syntactic knowledge, and orthographic knowledge are related to comprehension monitoring and whether comprehension monitoring mediates the relations between these language skills and reading comprehension. Eighty-nine Chinese children were assessed on their vocabulary, syntactic knowledge, orthographic knowledge, and comprehension monitoring in Grade 1. Their reading comprehension skills were assessed in Grade 1 and Grade 3. Results showed that in Grade 1, comprehension monitoring mediated the relations between vocabulary and syntactic knowledge and reading comprehension. For Grade 3 (...) reading comprehension, syntactic knowledge in Grade 1 was the only significant predictor. These findings indicate that multiple language skills make direct and indirect contributions via comprehension monitoring to Chinese reading comprehension, and the relations would change as children’s reading skills develop. (shrink)

In the course of an immune response, antibodies undergo affinity maturation in order to increase their efficiency in neutralizing foreign invaders. Affinity maturation occurs by the introduction of multiple point mutations in the variable region gene that encodes the antigen binding site. This somatic hypermutation is restricted to immunoglobulin genes and occurs at very high rates. The precise molecular basis of this process remains obscure. However, recent studies using a variety of in vivo and in vitro systems have revealed important (...) regulatory regions, base motifs that are preferred targets of mutation and evidence that transcription may play an active role in hypermutation. BioEssays 20:227–234, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

What are the processes, from conception to adulthood, that enable a single cell to grow into a sentient adult? Neuroconstructivism is a pioneering 2 volume work that sets out a whole new framework for considering the complex topic of development, integrating data from cognitive studies, computational work, and neuroimaging.

Neuroconstructivism: How the Brain Constructs Cognition proposes a unifying framework for the study of cognitive development that brings together (1) constructivism (which views development as the progressive elaboration of increasingly complex structures), (2) cognitive neuroscience (which aims to understand the neural mechanisms underlying behavior), and (3) computational modeling (which proposes formal and explicit specifications of information processing). The guiding principle of our approach is context dependence, within and (in contrast to Marr [1982]) between levels of organization. We propose that three (...) mechanisms guide the emergence of representations: competition, cooperation, and chronotopy; which themselves allow for two central processes: proactivity and progressive specialization. We suggest that the main outcome of development is partial representations, distributed across distinct functional circuits. This framework is derived by examining development at the level of single neurons, brain systems, and whole organisms. We use the terms encellment, embrainment, and embodiment to describe the higher-level contextual influences that act at each of these levels of organization. To illustrate these mechanisms in operation we provide case studies in early visual perception, infant habituation, phonological development, and object representations in infancy. Three further case studies are concerned with interactions between levels of explanation: social development, atypical development and within that, developmental dyslexia. We conclude that cognitive development arises from a dynamic, contextual change in embodied neural structures leading to partial representations across multiple brain regions and timescales, in response to proactively specified physical and social environment. (shrink)

What are the processes, from conception to adulthood, that enable a single cell to grow into a sentient adult? The processes that occur along the way are so complex that any attempt to understand development necessitates a multi-disciplinary approach, integrating data from cognitive studies, computational work, and neuroimaging - an approach till now seldom taken in the study of child development. Neuroconstructivism is a major new 2 volume publication that seeks to redress this balance, presenting an integrative new framework for (...) considering development. In the first volume, the authors review up-to-to date findings from neurobiology, brain imaging, child development, computer and robotic modelling to consider why children's thinking develops the way it does. They propose a new synthesis of development that is based on 5 key principles found to operate at many levels of descriptions. They use these principles to explain what causes a number of key developmental phenomena, including infants' interacting with objects, early social cognitive interactions, and the causes of dyslexia. The "neuroconstructivist" framework also shows how developmental disorders do not arise from selective damage to the normal cognitive system, but instead arise from developmental processes that operate under atypical constraints. How these principles work is illustrated in several case studies ranging from perceptual to social and reading development. Finally, the authors use neuroimaging, behavioural analyses, computational simulations and robotic models to provide a way of understanding the mechanisms and processes that cause development to occur. (shrink)

A central pillar of Carpendale & Lewis's (C&L's) argument is Wittgenstein's later work on language. I suggest that this support is not as strong as might be wished, and offer an alternative approach to their conclusion that language learning, especially of folk psychology, involves a socially embedded constructivism.

Mark, G. La crisis de la física clásica por obra del experimento.--Thirring, J. La transformación del sistema conceptual de la física.--Hahn, J. La crisis de la intuición.--Nöbeling, J. La cuarta dimensión y el espacio curvo.--Menger, C. La nueva lógica.

In addition to considering sociocultural, political, economic, and ethical factors, effectively engaging socioscientific issues requires that students understand and apply scientific explanations and the nature of science. Promoting such understandings can be achieved through immersing students in authentic real-world contexts where the SSI impacts occur and teaching those students about how scientists comprehend, research, and debate those SSI. This triangulated mixed-methods investigation explored how 60 secondary students’ trophic cascade explanations changed through their experiencing place-based SSI instruction focused on the Yellowstone (...) wolf reintroduction, including scientists’ work and debates regarding that issue. Furthermore, this investigation determined the association between the students’ post place-based SSI instruction trophic cascade explanations and NOS views. Findings from this investigation demonstrate that through the place-based SSI instruction students’ trophic cascade explanations became significantly more accurate and complex and included more ecological causal mechanisms. Also, significant and moderate to moderately large correlations were found between the accuracy and contextualization of students’ post place-based SSI instruction NOS views and the complexity of their trophic cascade explanations. Empirical substantiation of the association between the complexity of students’ scientific explanations and their NOS views responds to an understudied area in the science education research. It also encourages the consideration of several implications, drawn from this investigation’s findings and others’ prior work, which include the need for NOS to be forefront alongside and in connection with science content in curricular standards and through instruction focused on relevant and authentic place-based SSI. (shrink)

In this response, we consider four main issues arising from the commentaries to the target article. These include further details of the theory of interactive specialization, the relationship between neuroconstructivism and selectionism, the implications of neuroconstructivism for the notion of representation, and the role of genetics in theories of development. We conclude by stressing the importance of multidisciplinary approaches in the future study of cognitive development and by identifying the directions in which neuroconstructivism can expand in the Twenty-first Century.

Objectives: To study the attitudes of both medical and non-medical students towards the do-not-resuscitate decision in a university in Hong Kong, and the factors affecting their attitudes.Methods: A questionnaire-based survey conducted in the campus of a university in Hong Kong. Preferences and priorities of participants on cardiopulmonary resuscitation in various situations and case scenarios, experience of death and dying, prior knowledge of DNR and basic demographic data were evaluated.Results: A total of 766 students participated in the study. There were statistically (...) significant differences in their DNR decisions in various situations between medical and non-medical students, clinical and preclinical students, and between students who had previously experienced death and dying and those who had not. A prior knowledge of DNR significantly affected DNR decision, although 66.4% of non-medical students and 18.7% of medical students had never heard of DNR. 74% of participants from both medical and non-medical fields considered the patient’s own wish as the most important factor that the healthcare team should consider when making DNR decisions. Family wishes might not be decisive on the choice of DNR.Conclusions: Students in medical and non-medical fields held different views on DNR. A majority of participants considered the patient’s own wish as most important in DNR decisions. Family wishes were considered less important than the patient’s own wishes. (shrink)

The purpose of this study was to develop a Physician's Spiritual Well-Being Scale (PSpWBS). The significance of a physician's spiritual well-being was explored through in-depth interviews with and qualitative data collection from focus groups. Based on the results of qualitative analysis and related literature, the PSpWBS consisting of 25 questions was established. Reliability and validity tests were performed on 177 subjects. Four domains of the PSpWBS were devised: physician's characteristics; medical practice challenges; response to changes; and overall well-being. The explainable (...) total variance was 65.65%. Cronbach α was 0.864 when the internal consistency of the whole scale was calculated. Factor analysis showed that the internal consistency Cronbach α value for each factor was between 0.625 and 0.794 and the split-half reliability was 0.865. The scale has satisfactory reliability and validity and could serve as the basis for assessment of the spiritual well-being of a physician. (shrink)

A novel Protocol Ethics Tool Kit (‘Ethics Tool Kit’) has been developed by a multi-stakeholder group of the Multi-Regional Clinical Trials Center of Brigham and Women9s Hospital and Harvard. The purpose of the Ethics Tool Kit is to facilitate effective recognition, consideration and deliberation of critical ethical issues in clinical trial protocols. The Ethics Tool Kit may be used by investigators and sponsors to develop a dedicated Ethics Section within a protocol to improve the consistency and transparency between clinical trial (...) protocols and research ethics committee reviews. It may also streamline ethics review and may facilitate and expedite the review process by anticipating the concerns of ethics committee reviewers. Specific attention was given to issues arising in multinational settings. With the use of this Tool Kit, researchers have the opportunity to address critical research ethics issues proactively, potentially speeding the time and easing the process to final protocol approval. (shrink)

Metabolic pathways underlying brain function remain largely unexplored during neurodevelopment, predominantly due to the lack of feasible techniques for use with awake infants. Broadband near-infrared spectroscopy provides the opportunity to explore the relationship between cerebral energy metabolism and blood oxygenation/haemodynamics through the measurement of changes in the oxidation state of mitochondrial respiratory chain enzyme cytochrome-c-oxidase alongside haemodynamic changes. We used a bNIRS system to measure ΔoxCCO and haemodynamics during functional activation in a group of 42 typically developing infants aged between (...) 4 and 7 months. bNIRS measurements were made over the right hemisphere over temporal, parietal and central cortical regions, in response to social and non-social visual and auditory stimuli. Both ΔoxCCO and Δ[HbO2] displayed larger activation for the social condition in comparison to the non-social condition. Integration of haemodynamic and metabolic signals revealed networks of stimulus-selective cortical regions that were not apparent from analysis of the individual bNIRS signals. These results provide the first spatially resolved measures of cerebral metabolic activity alongside haemodynamics during functional activation in infants. Measuring synchronised changes in metabolism and haemodynamics have the potential for uncovering the development of cortical specialisation in early infancy. (shrink)

In the atavistic model of cancer progression, tumor cell dedifferentiation is interpreted as a reversion to phylogenetically earlier capabilities. The more recently evolved capabilities are compromised first during cancer progression. This suggests a therapeutic strategy for targeting cancer: design challenges to cancer that can only be met by the recently evolved capabilities no longer functional in cancer cells. We describe several examples of this target‐the‐weakness strategy. Our most detailed example involves the immune system. The absence of adaptive immunity in immunosuppressed (...) tumor environments is an irreversible weakness of cancer that can be exploited by creating a challenge that only the presence of adaptive immunity can meet. This leaves tumor cells more vulnerable than healthy tissue to pathogenic attack. Such a target‐the‐weakness therapeutic strategy has broad applications, and contrasts with current therapies that target the main strength of cancer: cell proliferation. (shrink)

What are the processes, from conception to adulthood, that enable a single cell to grow into a sentient adult? The processes that occur along the way are so complex that any attempt to understand development necessitates a multi-disciplinary approach, integrating data from cognitive studies, computational work, and neuroimaging - an approach till now seldom taken in the study of child development. Neuroconstructivism is a major new 2 volume publication that seeks to redress this balance, presenting an integrative new framework for (...) considering development. In the first volume, the authors review up-to-to date findings from neurobiology, brain imaging, child development, computer and robotic modelling to consider why children's thinking develops the way it does. They propose a new synthesis of development that is based on 5 key principles found to operate at many levels of descriptions. They use these principles to explain what causes a number of key developmental phenomena, including infants' interacting with objects, early social cognitive interactions, and the causes of dyslexia. The "neuroconstructivist" framework also shows how developmental disorders do not arise from selective damage to normal cognitive systems, but instead arise from developmental processes that operate under atypical constraints. How these principles work is illustrated in several case studies ranging from perceptual to social and reading development. Finally, the authors use neuroimaging, behavioural analyses, computational simulations and robotic models to provide a way of understanding the mechanisms and processes that cause development to occur. Computer and robotic models provide concrete tools for investigating the processes and mechanisms involved in learning and development. Volume 2 illustrates the principles of 'Neuroconstructivist' development, with contributions from 9 different labs across the world. Each of the contributions illustrates how models play a central role in understanding development. The models presented include standard connectionist neural network models as well as multi-agent models. Also included are robotic models emphasizing the need to take embodiment and brain-system interactions seriously. A model of Autism and one of Specific Language Impairment also illustrate how atypical development can be understood in terms of the typical processes of development but operating under restricted conditions. This volume complements Volume 1 by providing concrete examples of how the 'Neuroconstructivist' principles can be grounded within a diverse range of domains, thereby shaping the research agenda in those domains. (shrink)

The view that human law can be analyzed in terms of commands was subjected to devastating criticism by H. L. A. Hart in his 1961 The Concept of Law. Two objections that Hart levels against the command theory of law also make serious trouble for divine command theory. Divine command theorists would do well to jettison command as the central concept of their moral theory and, following Hart’s lead, instead appeal to the concept of a rule. Such a successor view—divine (...) legislation theory—has the attractions of divine command theory without the unacceptable limitations of command theories that Hart identifies. (shrink)

Introduction: Probationers, offenders with less serious and non-violent offences, and under statutory supervision, have low levels of self-esteem and physical health, and high level of family conflict, and poorer quality of family relationships. This study examined the effectiveness of the existing probation service and the additional use of a positive family holistic health intervention to enhance physical, psychological, and family well-being in probationers and relationships with probation officers.Methods: Probationers under the care of the Hong Kong Social Welfare Department were randomized (...) into a care-as-usual control group, a brief intervention group receiving two 1-h individual sessions [of a brief theory-based positive family holistic health intervention integrating Zero-time Exercise and positive psychology themes of “Praise and Gratitude” in the existing probation service], or a combined intervention group receiving BI and a 1-day group activity with family members. The outcomes were physical activity, fitness performance, self-esteem, happiness, anxiety and depression symptoms, life satisfaction, quality of life, family communication and well-being, and relationships with probation officers. Self-administered questionnaires and simple fitness tests were used at baseline, 1-month and 3-month follow-up. Linear mixed model analysis was used to compare difference in the changes of outcome variables among groups, adjusted of sex, age, and baseline values. Focus group interviews were conducted. Thematic content analysis was used.Results: 318 probationers were randomized into CAU, BI, or CI group. CAU showed enhanced physical activity, fitness performance and psychological health, and family communication with small effect sizes. BI and CI showed further improved physical activity, family communication and family well-being. Additionally, CI reported greater improvements in the relationships with probation officers than CAU with a small effect size. CI also reported greater increases in physical activity and family communication than BI with small to moderate effect sizes. Qualitative feedbacks corroborated the quantitative findings.Conclusion: Our trial provided the first evidence of the effectiveness of probation service and the additional use of an innovative, relatively low-cost, theory-based brief positive family holistic health intervention. This intervention may offer a new model for enhancing probation service.Trial Registration: The research protocol was registered at the National Institutes of Health. (shrink)

The Ontology for Biomedical Investigations (OBI) is an ontology that provides terms with precisely defined meanings to describe all aspects of how investigations in the biological and medical domains are conducted. OBI re-uses ontologies that provide a representation of biomedical knowledge from the Open Biological and Biomedical Ontologies (OBO) project and adds the ability to describe how this knowledge was derived. We here describe the state of OBI and several applications that are using it, such as adding semantic expressivity to (...) existing databases, building data entry forms, and enabling interoperability between knowledge resources. OBI covers all phases of the investigation process, such as planning, execution and reporting. It represents information and material entities that participate in these processes, as well as roles and functions. Prior to OBI, it was not possible to use a single internally consistent resource that could be applied to multiple types of experiments for these applications. OBI has made this possible by creating terms for entities involved in biological and medical investigations and by importing parts of other biomedical ontologies such as GO, Chemical Entities of Biological Interest (ChEBI) and Phenotype Attribute and Trait Ontology (PATO) without altering their meaning. OBI is being used in a wide range of projects covering genomics, multi-omics, immunology, and catalogs of services. OBI has also spawned other ontologies (Information Artifact Ontology) and methods for importing parts of ontologies (Minimum information to reference an external ontology term (MIREOT)). The OBI project is an open cross-disciplinary collaborative effort, encompassing multiple research communities from around the globe. To date, OBI has created 2366 classes and 40 relations along with textual and formal definitions. The OBI Consortium maintains a web resource providing details on the people, policies, and issues being addressed in association with OBI. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Hume Studies Volume XXIII, Number 2, November 1997, pp. 227-244 Hume on Geometry and Infinite Divisibility in the Treatise H. MARK PRESSMAN Scholars have recognized that in the Treatise "Hume seeks to find a foundation for geometry in sense-experience."1 In this essay, I examine to what extent Hume succeeds in his attempt to ground geometry visually. I argue that the geometry Hume describes in the Treatise faces a (...) serious set of problems. Geometric Lines Hume maintains that ideas "are images" (T 6) which may be called up "when I shut my eyes" (T 3). "That we may fix the meaning of a word, figure," according to Hume, "we may revolve in our mind the ideas of circles, squares, parallelograms, triangles of different sizes and proportions, and may not rest on one image or idea" (T 22). As Arthur Pap notes, "'Idea' is in Hume's usage synonymous with 'mental image'." D.C.G. MacNabb also notes that "Hume thought of ideas as images, and primarily as visual images."2 When Hume argues, then, that "we have the idea of indivisible points, lines and surfaces conformable to the [geometer's] definition" (T 44), he is arguing that we have mental images of geometry's points, lines and planes. Consider geometric lines first. Geometers define a line "to be length without breadth or depth" (T 42). It is not apparent to everyone that we have mental images of such lines. According to "L'Art de penser" (T 43), published in 1662, it is impossible "to conceive a length without any breadth" (T 43). H. Mark Pressman is at the Department of Philosophy, University of California, Davis, 1238 Social Sciences and Humanities Building, Davis CA 95616-8673 USA. email: [email protected] 228 H. Mark Pressman We can only by an abstraction "consider the one without regarding the other" (T 43). Hume, however, offers "clear proof" (T 44), in the form of two arguments, that we actually possess ideas or mental images of geometry's lines. First, we have ideas or mental images of lengths with breadth, though these are supposed never to be without breadth and thus not geometric lines. (A mental image oflength is also a mental image with length, just as "to say the idea of extension agrees to any thing, is to say it is extended" [T 240].) Hume reduces to absurdity the view that our mental images of length are always with breadth and thus not images of geometric lines. If our length-images were always with breadth, then our mental images would be endlessly divisible in breadth, since they would always have some positive breadth (T 43). But no mental image is endlessly divisible, for the mind arrives "at an end in the division of its ideas, nor are there any possible means of evading the evidence of this conclusion" (T 27). We thus have an idea or image of length without (divisible) breadth conforming to the geometer's definition (T 44). Second, we can imagine or picture the termination of a geometric plane. But a geometric plane must terminate in a geometric line (T 44). (Proof: Assume L is a line with breadth which terminates plane P. Since L has breadth, L must contain at least two parts, w and y, exactly one of which actually terminates P. But whether it is w or y, L doesn't terminate P, which was the assumption.) Since we can picture the termination of a geometric plane, we can picture a geometric line, length without divisible breadth. It is one thing to have ideas or mental images of geometric lines which may be called up "when I shut my eyes" (T 3). It is another for such objects actually to exist "in nature." The conceptualist holds that though (a) geometry 's points, lines and planes are ideas, nevertheless (b) there are no such things in nature and that (c) there can't be such things in nature: [T]he objects of geometry... are mere ideas in the mind, and not only never did, but never can exist in nature. They never did exist; for no one will pretend to draw a line or make a... (shrink)

This book has been written in the hopes of equipping teachers-in-training—that is, teacher candidates—with the skills needed for action research: a process that leads to focused, effective, and responsive strategies that help students succeed.

The academic literature in research ethics has been marked in the past decade by a much broader focus on the need for the protection of developing communities subjected to international clinical trials. Because of the proximity of the revision of the Declaration of Helsinki, completed in October 2008, most papers have addressed the issue of a double standard of care following the use of placebo. However, other no less important issues, such as interactions between the lifestyles structures of low-income communities (...) and the efficiency of risk-minimising procedures also deserve attention. The purpose of this paper is to discuss forms of uncertainty involved in clinical trials in poor and low-income countries that are not addressed by conventional methods of risk assessment. Furthermore, the increase in size of risks that are identified by conventional assessment methods will be addressed. Besides, the difficulty in properly applying risk-minimising procedures will be discussed. Finally, this paper proposes the involvement of research ethics committees in the risk evaluation process and the establishment of national ethics evaluation systems. (shrink)

Three standard psychometric tests were administered to parents who volunteered their children for a randomised, double-blind placebo-controlled trial of a new asthma drug and to a control group of parents whose children were eligible for the trial but had declined the invitation. The trial took place at a children's hospital in Australia. The subjects comprised 68 parents who had volunteered their children and 42 who had not, a participation rate of 94 per cent and 70 per cent, respectively. The responses (...) of these parents to the Gordon Survey of Interpersonal Values Questionnaire, the Coopersmith Self-Esteem Inventory and the Cattell Sixteen Personality Factor Questionnaire were analysed by computer. There was a marked difference between the psychological profiles of the two groups of parents. Volunteering parents put more value on benevolence while non-volunteering parents were more concerned with power and prestige. The self-esteem of volunteering parents was much lower than that of non-volunteering parents. Finally, volunteering parents were more introverted, exhibited greater anxiety and low supergo, while non-volunteering parents appeared to have greater social confidence and emotional stability. Since an individual's values, self-esteem and personality may be important antecedents of behaviour, these findings suggest that parents who volunteer their children for clinical research are not only socially disadvantaged and emotionally vulnerable, but may also be psychologically predisposed to volunteering. Furthermore, these findings provide evidence for the existence of a psychosocial 'filter' effect of the informed consent procedure, which may be discouraging the better educated, more privileged and psychologically resilient members of society from participation as research subjects. (shrink)

Almost everybody has a conscience, though it may not play a dominating or even very prominent role in his life. To have a conscience is to classify some kinds of action as morally right and others as morally wrong, and to be disposed to do the former and avoid doing the latter. To judge an action as morally right or wrong is not to judge it as advantageous or disadvantageous to the agent; the motive for acting conscientiously cannot be pure (...) self-interest. It is a mark of my thinking an action morally right that I am disposed to do it even though doing it will involve me in a net loss of enjoyment or a net surplus of suffering. A man who is only disposed to do such things as he thinks will increase his happiness in the long run has no conscience. Conscience presents itself to a person as a kind of constraint which he cannot evade on the ground that it will be inconvenient to comply with it. (shrink)

The health co-benefits of CO2 mitigation can provide a strong incentive for climate policy through reductions in air pollutant emissions that occur when targeting shared sources. However, reducing air pollutant emissions may also have an important co-harm, as the aerosols they form produce net cooling overall. Nevertheless, aerosol impacts have not been fully incorporated into cost-benefit modeling that estimates how much the world should optimally mitigate. Here we find that when both co-benefits and co-harms are taken fully into account, optimal (...) climate policy results in immediate net benefits globally, overturning previous findings from cost-benefit models that omit these effects. The global health benefits from climate policy could reach trillions of dollars annually, but will importantly depend on the air quality policies that nations adopt independently of climate change. Depending on how society values better health, economically optimal levels of mitigation may be consistent with a target of 2 °C or lower. (shrink)

This book celebrates the work of Patricia Werhane, an iconic figure in business ethics. This festschrift is a collection of articles that build on Werhane’s contributions to business ethics in such areas as Employee Rights, the Legacy of Adam Smith, Moral Imagination, Women in Business, the development of the field of business ethics, and her contributions to such fields as Health Care, Education, Teaching, and Philosophy. All papers are new contributions to the management literature written by well-known business ethicists, such (...) as Norman Bowie, Richard De George, Ronald Duska, Edwin Hartman, Michael Hoffman, Mollie Painter-Morland, Mark Schwartz, Andrew Wicks, and others. The volume is comprised of articles that reflect on Werhane’s work as well as build on it as a way to advance further research. At the end of the festschrift, Pat Werhane provides responses to each chapter. The first chapter of the book also includes the overview of Patricia Werhane’s work and her academic career. The book is written to appeal to management scholars and graduate students interested in the areas of Business Ethics, Modern Capitalism, and Human Rights. Patricia Werhane is one of the most distinguished figures in the field of business ethics. She was a founder of the field, she is one of its leading scholars, and she has had a profound impact on the world of business practice. Among her many accomplishments, Pat is known for her original work on moral imagination, she is an acclaimed authority on employee rights in the workplace, and she is one of the leading scholars on Adam Smith. Having been active in Academia for over 50 years, Werhane is a prolific author of over a hundred articles and book chapters, and the author or editor of twenty-seven books, including Adam Smith and his Legacy for Modern Capitalism, Moral Imagination and Management Decision-Making, and co-authored books Organization Ethics in Health Care, Alleviating Poverty Through Profitable Partnerships, Obstacles to Ethical Decision-Making, Corporate Responsibility: The American Experience, and Research Approaches to Business Ethics and Corporate Responsibility. (shrink)

About one third of patients with epilepsy have seizures refractory to the medical treatment. Electrical stimulation mapping is the gold standard for the identification of “eloquent” areas prior to resection of epileptogenic tissue. However, it is time-consuming and may cause undesired side effects. Broadband gamma activity recorded with extraoperative electrocorticography during cognitive tasks may be an alternative to ESM but until now has not proven of definitive clinical value. Considering their role in cognition, the alpha and beta bands could further (...) improve the identification of eloquent cortex. We compared gamma, alpha and beta activity, and their combinations for the identification of eloquent cortical areas defined by ESM. Ten patients with intractable focal epilepsy participated in a delayed-match-to-sample task, where syllable sounds were compared to visually presented letters. We used a generalized linear model approach to find the optimal weighting of each band for predicting ESM-defined categories and estimated the diagnostic ability by calculating the area under the receiver operating characteristic curve. Gamma activity increased more in eloquent than in non-eloquent areas, whereas alpha and beta power decreased more in eloquent areas. Diagnostic ability of each band was close to 0.7 for all bands but depended on multiple factors including the time period of the cognitive task, the location of the electrodes and the patient’s degree of attention to the stimulus. We show that diagnostic ability can be increased by 3–5% by combining gamma and alpha and by 7.5–11% when gamma and beta were combined. We then show how ECoG power modulation from cognitive testing can be used to map the probability of eloquence in individual patients and how this probability map can be used in clinical settings to optimize ESM planning. We conclude that the combination of gamma and beta power modulation during cognitive testing can contribute to the identification of eloquent areas prior to ESM in patients with refractory focal epilepsy. (shrink)

ObjectiveTo prospectively study the cingulate cortex for the localization and role of the grasping action in humans during electrical stimulation of depth electrodes.MethodsAll the patients with intractable focal epilepsy and a depth electrode stereotactically placed in the cingulate cortex, as part of their pre-surgical epilepsy evaluation from 2015 to 2017, were included. Cortical stimulation was performed and examined for grasping actions. Post-implantation volumetric T1 MRIs were co-registered to determine the exact electrode position.ResultsFive patients exhibited contralateral grasping actions during electrical stimulation. (...) All patients had electrodes implanted in the ventral bank of the right cingulate sulcus adjacent to the vertical anterior commissure line. Stimulation of other electrodes in adjacent regions did not elicit grasping.ConclusionGrasping action elicited from a localized region in the mid-cingulate cortex directly supports the concept of the cingulate cortex being crucially involved in the grasping network. This opens an opportunity to explore this region with deep brain stimulation as a motor neuromodulation target for treatment in specific movement disorders or neurorehabilitation. (shrink)

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 the UK, current policies and services for people with mental disorders, including those with intellectual disabilities (ID), presume that these men and women can, do, and should, make decisions for themselves. The new Mental Capacity Act (England and Wales) 2005 (MCA) sets this presumption into statute, and codifies how decisions relating to health and welfare should be made for those adults judged unable to make one or more such decisions autonomously. The MCA uses a procedural checklist to guide this (...) process of substitute decision-making. The personal experiences of providing direct support to seven men and women with ID living in residential care, however, showed that substitute decision-making took two forms, depending on the type of decision to be made. The first process, ‘strategic substitute decision-making’, paralleled the MCA’s legal and ethical framework, whilst the second process, ‘relational substitute decision-making’, was markedly different from these statutory procedures. In this setting, ‘relational substitute decision-making’ underpinned everyday personal and social interventions connected with residents’ daily living, and was situated within a framework of interpersonal and interdependent care relationships. The implications of these findings for residential services and the implementation of the MCA are discussed. (shrink)