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)

This article discusses the body of work produced in the 1920–1930s by the Cosmist philosophers Alexander Gorsky, Nikolai Setnitsky, and Valeryan Muravyov as a representative case of the interaction between philosophy and literature typical for the Russian culture in the nineteenth to twentieth centuries. The article demonstrates how the synthesizing nature of the Cosmists’ creative thought, along with the multiplicity of their cultural roles, led to their use of genre forms which combined two types of writing, the literary and (...) the philosophical, namely, philosophical mystery plays, philosophical poems, aphorisms, and fragments. In addition, their aesthetic views and creative productions are shown in connection with the philosophical legacy of Nikolai Fedorov, who explored the notions of “projective culture,” of history as salvatory work, and of art as a re-creation of life. This study of poetry and prose of Gorsky, Setnitsky and Muravyov reveals the links between their aesthetic views, which were based on the notion of “cultural Central Image”, and their creative practices. (shrink)

This is a welcome reprint of a book that continues to grow in importance.

The author presents and defends three theses: (1) "the first is that it is not profitable for us at present to do moral philosophy; that should be laid aside at any rate until we have an adequate philosophy of psychology." (2) "the second is that the concepts of obligation, And duty... And of what is morally right and wrong, And of the moral sense of 'ought', Ought to be jettisoned if this is psychologically possible...." (3) "the third thesis is that (...) the differences between the well-Known english writers on moral philosophy from sidgwick to the present day are of little importance." (staff). (shrink)

This paper analyses whether current explainable AI (XAI) techniques can help to address taxpayer concerns about the use of AI in taxation. As tax authorities around the world increase their use of AI-based techniques, taxpayers are increasingly at a loss about whether and how the ensuing decisions follow the procedures required by law and respect their substantive rights. The use of XAI has been proposed as a response to this issue, but it is still an open question whether current XAI (...) techniques are enough to meet existing legal requirements. The paper approaches this question in the context of a case study: a prototype tax fraud detector trained on an anonymized dataset of real-world cases handled by the Buenos Aires (Argentina) tax authority. The decisions produced by this detector are explained through the use of various classification methods, and the outputs of these explanation models are evaluated on their explanatory power and on their compliance with the legal obligation that tax authorities provide the rationale behind their decision-making. We conclude the paper by suggesting technical and legal approaches for designing explanation mechanisms that meet the needs of legal explanation in the tax domain. (shrink)

This book offers an introduction to the Sophists of fifth-century Athens and a new overall interpretation of their thought. Since Plato first animadverted on their activities, the Sophists have commonly been presented as little better than intellectual mountebanks - a picture which Professor Kerferd forcefully challenges here. Interpreting the evidence with care, he shows them to have been part of an exciting and historically crucial intellectual movement. At the centre of their teaching was a form of relativism, most famously expressed (...) by Protagoras as 'Man is the measure of all things', and which they developed in a wide range of views - on knowledge and argument, virtue, government, society, and the gods. On all these subjects the Sophists did far more than simply provoke Plato to thought. Their contributions were substantial and serious; they inaugurated the debate on many central philosophical questions and decisively shifted the focus of philosophical attention from the cosmos to man. (shrink)

I introduce definition by genus and specific difference, afterwards using it to show that Karl Jaspers rejected the classic criteria for pathologically falsified judgment: ‘Absolute conviction,’ ‘incorrigibility,’ and ‘impossibility of content.’ Next I draw attention to the primary experience of delusion. Famously, Jaspers reckoned that that experience was “ununderstandable”—usually taken to imply something negative about one’s ability to empathize with the delusion holder. All the same, I propose that it was actually our static mode of understanding that he felt was (...) defeated by the aforementioned experience, not our genetic one. (shrink)

Medical practice is ideally based on robust, relevant research. However, the lack of disease-modifying treatments for Alzheimer’s disease has motivated “innovative practice” to improve patients’ well-being despite insufficient evidence for the regular use of such interventions in health systems treating millions of patients. Innovative or new non-validated practice poses at least three distinct ethical questions: first, about the responsible application of new non-validated practice to individual patients ; second, about the way in which data from new non-validated practice are communicated (...) via the scientific and lay press ; and third, about the prospect of making new non-validated interventions widely available before more definitive testing. We argue that the authors of metabolic enhancement protocols for Alzheimer’s disease have overstated the evidence in favor of these interventions within the scientific and lay press, failing to communicate weaknesses in their data and uncertainty about their conclusions. Such unmeasured language may create false hope, cause financial harm, undermine informed consent, and frustrate the production of generalizable knowledge necessary to face the societal problems posed by this devastating disease. We therefore offer more stringent guidelines for responsible innovation in the treatment of Alzheimer’s disease. (shrink)

I introduce definition by genus and specific difference, afterwards using it to show that Karl Jaspers rejected the classic criteria for pathologically falsified judgment: ‘Absolute conviction,’ ‘incorrigibility,’ and ‘impossibility of content.’ Next I draw attention to the primary experience of delusion. Famously, Jaspers reckoned that that experience was “ununderstandable”—usually taken to imply something negative about one’s ability to empathize with the delusion holder. All the same, I propose that it was actually our static mode of understanding that he felt was (...) defeated by the aforementioned experience, not our genetic one. (shrink)

Este articulo analiza el proceso de integración del Mercosur en el que participan Argentina, Brasil, Paraguay y Uruguay y sus efectos sobre la ciudadanía política y social. En la primera parte del mismo los autores examinan los rasgos, el contexto de nacimiento y la filos ofía del proceso de integración mercosureño. La segunda parte analiza la evoluciónde la democracia y de la justicia social durante el proceso de integración. Los autores llegan a la conclusión de que el modelo de integración (...) mercosureño no puede contrarrestar la crisis de la democracia y de la justicia social que tienen lugar especialmente en Argentina y Brasil. (shrink)

The contemporary sociology of morality is a form of descriptive ethics that shrinks away from any sort of prescriptive ethics. Building on the moral philosophies of John Dewey, and also of Alasdair MacIntyre and Paul Ricoeur, and in dialogue with recent work by Stefan Bargheer, this article proposes a more ambitious program of critical social ethics that connects concerns with character and the common good but tempers them with attention to alienation and oppression.

Normal propositional modal systems This first chapter has two main aims. One is to give a general account of the propositional modal systems that we shall ...

The opinions expressed herein are those of the author and do not necessarily reflect the policies of the Office of Research Integrity, U.S.Department of Health, or any other Federal agency.

An examination of verbal hallucinations and thought insertion as examples of "alienated self-consciousness.".

This book traces the intellectual revolution initiated by Thales in the sixth century BC to its culmination in the metaphysics of Parmenides.

ABSTRACT This text aims to reflect on why speech genres are relevant to variation studies, especially for third wave studies, whose central issue is the notion of style. Through bibliographic research, we examine part of the literature of the third wave of variation studies and part of the literature of the Bakhtinian approach, focusing on the notion of style, to (i) highlight some connections between these approaches and to (ii) articulate them, in some other points. The results of this reflection (...) indicate that speech genres are relevant to the interests of third wave studies because (i) linguistic style is a property of speech genres, upgradeable due to the aesthetic finalizations they receive; and (ii) an understanding of style requires an understanding of the (social and formal) constitution of the genres, in which categories of analysis that are of interest to the third wave of variation studies are indicated. (shrink)

BackgroundExpanded access is the use of investigational drugs (IDs) outside of clinical trials. Generally it is performed in patients with serious and life-threatening diseases who cannot be treated satisfactorily with authorized drugs. Legal regulations of expanded access to IDs have been introduced among others in the USA, the European Union (EU), Canada and Australia. In addition, in the USA an alternative to expanded access is treatment under the Right-to-Try law. However, the treatment use of IDs is inherently associated with a (...) number of ethically relevant problems.Main textThe objective of this article is to present a coherent framework made up of eight requirements which have to be met for any treatment use of an ID to be ethical. These include a justified need for the use of an ID, no threat to clinical development of the ID, adequate scientific evidence to support the treatment, patient’s benefit as the primary goal of the use of an ID, informed decision of a patient, fair access of patients to IDs, independent review, as well as the dissemination of treatment results.ConclusionsWhile this framework is essentially consistent with the legal regulations of expanded access of the USA, the EU, Canada and Australia, it is substantially wider in scope because it addresses some important issues that are not covered by the regulations. Overall, the framework that we developed minimizes the risks and threats, and maximizes potential benefits to each of the four key stakeholders involved in the treatment use of IDs including patients, doctors, drug manufacturers, and society at large. (shrink)

The technological advances of the 20th century resulted in the creation of the Internet and its introduction into everyday life on a global scale. The Internet provides access to information and the sale and purchase of goods. Medications are also subject to trade. Their sale is conducted by online pharmacies and their global turnover amounts to hundreds of billions of dollars. Medications ordered over the Internet are sent by mail all over the world. Considering the events of recent years, we (...) cannot exclude the risk of a terrorist attack through online pharmacies. Terrorists can establish such companies, legally or illegally, or acquire ones already existing. Parcels, which are highly trusted by the customers of online pharmacies, can, for example, be contaminated with dangerous materials. The sale of online medications in the international system is potentially dangerous and requires international regulation. (shrink)

In the light of a vast political information ‘buffet’, so-called news-avoiders stay away from the news for indefinite periods of time. Recent research suggests that news avoidance can be intentional or unintentional. However, research has mostly focused on one form of news avoidance or has not differentiated at all. Based on survey data, this study (a) identifies and compares motivations for intentional and unintentional avoidance and (b) investigates drivers of different news avoidance motives. Findings suggest that, overall, avoidance is rooted (...) in the preference for other pastimes, with intentional avoiders also being tired of news and seeing it as too negative, biased, and unreliable. Further, different motives are driven by specific characteristics: Political knowledge and internal efficacy relate to ‘cognitive’ motives, empathy, and being negativity-prone to ‘emotional’ motives, while external efficacy relates to ‘political’ motives. (shrink)

The concept of informed consent was one of the most fruitful ideas that deeply changed the relationships between physicians and their patients from paternalism to respect for the personal autonomy of subjects needing professional medical care. The great progress in medicine, also involving the pharmaceutical industry, has created an increasing need to perform different clinical and experimental trials. The evolution of clinical research in the last decades has influenced strongly the design of these studies. One of the most important changes (...) in this field has been the use of placebo groups in double-blind controlled studies. The controversies have involved not only the use of placebo when standard or proven treatment was available, but also some specific problems concerning the procedure of obtaining informed consent in such trials. This paper briefly presents the evolution of informed consent in Poland as well as different ethical and legal problems concerning informed consent and the use of placebo controls in clinical trials. (shrink)

Este artículo analiza el proceso de integración del Mercosur en el que participan Argentina, Brasil, Paraguay y Uruguay y sus efectos sobre la ciudadanía política y social. En la primera parte del mismo los autores examinan los rasgos, el contexto de nacimiento y la filosofía del proceso de integración mercosureño. La segunda parte analiza la evolución de la democracia y de la justicia social durante el proceso de integración. Los autores llegan a la conclusión de que el modelo de integración (...) mercosureño no puede contrarrestar la crisis de la democracia y de la justicia social que tienen lugar especialmente en Argentina y Brasil. (shrink)

La aprobación en junio de 2008 por el Parlamento Europeo de la Directiva de retorno —denominada también Directiva de la infamia o Directiva de expulsión— consolida el proceso de involución que sobre los derechos humanos se viene produciendo en la Unión Europea desde que el miedo a la inmigración irregular se incardinó en sus instituciones. Si bien las legislaciones de extranjería de los años ochenta contenían normas que regulaban el internamiento y la expulsión no es hasta la Directiva 2001/40/CE que (...) comienza a tomar forma una política comunitaria centrada en la inmigración irregular y las expulsiones de migrantes. Las medidas de retorno son, dice la Comisión europea, “una piedra angular de la política de migración de la UE”. Desde entonces, la barbarie de los centros de retención e internamiento, el socavamiento de los derechos y la exclusión y criminalización de los migrantes extranjeros se han convertido en el caballo de batalla de las asociaciones defensoras de los derechos humanos. La erosión que las legislaciones y medidas de expulsión están provocado en los derechos y libertades y en las instituciones del Estado de derecho es inmensa. El retroceso y la erosión en los derechos y libertades es tan grande que ya no es posible continuar hablando sin más de Estados de derecho en la UE, sino más bien de máquinas administrativas para el internamiento y la expulsión, de “Estados expulsores” (1), donde las personas extranjeras son tratadas como semipersonas (2) e incluso como “no-personas” (3). (shrink)

En esta contribución se analizan dos grandes períodos de la obra intelectual de Pietro Barcellona. El primero se corresponde con sus originarias reflexiones sobre los distintos usos del derecho, en el sentido de la transformación-adecuación de las instituciones y del ordenamiento jurídico italiano de la postguerra con los principios de la Constitución de 1948. De este primer período hay que destacar sus investigaciones sobre el uso alternativo del derecho y de los lazos de funcionalidad existentes entre el Estado, la economía (...) y el derecho. En el segundo período, se analiza el tránsito del pensamiento barcelloniano hacia las cuestiones que deben enriquecer un concepto de democracia plena de sentido para un individuo cada vez más alienado, sometido a la lógica de lo económico y, por tanto, menos libre y autónomo. Barcellona afronta esta última cuestión analizando los fundamentos de la Modernidad, para comprender principalmente dos cosas: a) el destino del individuo en esta fase de la sociedad occidental, y b) saber cómo ha logrado la burguesía, a través de qué principios y formas, consolidar y reproducir su hegemonía social en la sociedad moderna. En esta etapa el siguiente trabajo se centra, en primer lugar, en su teoría del individualismo propietario y en la crítica al "derecho igual", para después, en un segundo momento, plantear sus propuestas acerca de la política y de la democracia como forma de vida. Todo el análisis de la obra de Barcellona, considerada por los autores del siguiente ensayo, como fundamental para entender diversos aspectos jurídico-políticos de las sociedades post-industriales, ha sido desarrollado respetando el orden cronológico de la producción intelectual de Barcellona a lo largo de los dos períodos tratados. (shrink)