Although activated spinal cord glia contribute importantly to neuropathic pain, how nerve injury activates glia remains controversial. It has recently been proposed, on the basis of genetic approaches, that toll-like receptor 4 may be a key receptor for initiating microglial activation following L5 spinal nerve injury. The present studies extend this idea pharmacologically by showing that TLR4 is key for maintaining neuropathic pain following sciatic nerve chronic constriction injury. Established neuropathic pain was reversed by intrathecally delivered TLR4 receptor antagonists derived (...) from lipopolysaccharide. Additionally, -naltrexone, -naloxone, and -naloxone, which we show here to be TLR4 antagonists in vitro on both stably transfected HEK293-TLR4 and microglial cell lines, suppressed neuropathic pain with complete reversal upon chronic infusion. Immunohistochemical analyses of spinal cords following chronic infusion revealed suppression of CCI-induced microglial activation by -naloxone and -naloxone, paralleling reversal of neuropathic pain. Together, these CCI data support the conclusion that neuron-to-glia signaling through TLR4 is important not only for initiating neuropathic pain, as suggested previously, but also for maintaining established neuropathic pain. Furthermore, these studies suggest that the novel TLR4 antagonists -naloxone and -naloxone can each fully reverse established neuropathic pain upon multi-day administration. This finding with -naloxone is of potential clinical relevance. This is because -naloxone is an antagonist that is inactive at the -opioid selective receptors on neurons that produce analgesia. Thus, these data suggest that -opioid antagonists such as -naloxone may be useful clinically to suppress glial activation, yet -opioid agonists suppress pain. (shrink)

PURPOSE:To report the localization of a gene causing drusen and macular degeneration in a previously undescribed North American family. METHODS:Genetic mapping studies were performed using linkage analysis in a single family with drusen and atrophic macular degeneration. RESULTS:The clinical manifestations in this family ranged from fine macular drusen in asymptomatic middle-aged individuals to atrophic macular lesions in two children and two elderly patients. We mapped the gene to chromosome 6q14 between markers D6S2258 and D6S1644. CONCLUSIONS:In a family with autosomal dominant (...) drusen and atrophic macular degeneration, the gene maps to a 3.2-cM region on chromosome 6q14. This locus appears to be distinct from, but adjacent to, the loci for cone-rod dystrophy 7 (CORD7) and North Carolina macular dystrophy (MCDR1). Future identification of the gene responsible for the disease in this family will provide a better understanding of macular degeneration. (shrink)

Producing content-related gestures has been found to impact students’ learning, whether such gestures are spontaneously generated by the learner in the course of problem-solving, or participants are instructed to pose based on experimenter instructions during problem-solving and word learning. Few studies, however, have investigated the effect of (a) performing instructed gestures while learning concepts or (b) producing gestures without there being an implied connection between the gestures and the concepts being learned. The two studies reported here investigate the impact of (...) instructed hand movements on students’ subsequent understanding of a concept. Students were asked to watch an instructional video—focused on the concept of statistical model—three times. Two experimental groups were given a secondary task to perform while watching the video, which involved moving their hands to mimic the placement and orientation of red rectangular bars overlaid on the video. Students were told that the focus of the study was multitasking, and that the instructed hand movements were unrelated to the material being learned. In the content-match group the placement of the hands reinforced the concept being explained, and in the content-mismatch group it did not. A control group was not asked to perform a secondary task. In both studies, findings indicate that students in the content-match group performed better on the posttest, and showed less variation in performance, than did students in the content-mismatch group, with control students falling in between. Instructed hand movement—even when presented as an unrelated, secondary task—can affect students’ learning of a complex concept. (shrink)

Evidence from our research on young children's temporal understanding supports Hoerl & McCormack's view that young children rely on a temporal updating system to change representations over time. We propose that the shift from temporal updating to temporal reasoning is enabled by children's expanding representations of event sequences, along with developments in language, memory, and other cognitive competencies.

The article examines the new discourse on medical professionalism and responsibility through the prism of conflicts among moral values, especially with regard to truth-telling. The discussion is anchored in the renaissance of English-language writing on medical ethics in the 18th century, which paralleled the rise of humanitarianism and the advent of the word “responsibility”. Following an analysis of the meanings of the value of responsibility in general and in medical practice in particular, it is argued that, similarly to the Aristotelian (...) notion of equity, responsibility of care is a second-order value, which corrects virtues, laws and norms in exceptional circumstances. Virtues and practices of the second order, such as responsibility and deliberation, bear especially on professional doctoring, which includes a commitment to give priority to the good of the patient over one’s own good. It is argued that, in situations of conflict, and particularly conflicts between personal moral identity and the good of patients, the fundamental professional commitment is to critical and rational deliberation and to the cultivation of psycho-moral flexibility. This leads indirectly to moral growth and strengthening of professional character. (shrink)

The article surveys the history of “terror” vis a vis the development of international humanitarian and human rights law. During the French Revolution, the word “terror” was coined to describe a deviation from the laws of war. Justified by a mixture of ideology and necessity. People who resort to terrorism either suspends or rejects the laws of war (jus in bellum) in the name of an alternative and heightened sense of truth. However, the terrorists’ strong sense of probity and mission (...) is also an opening for re-establishing communication, arbitration and mitigation of cruelty and destruction. This paper represents International Humanitarian Law (IHL) as an “abstract Leviathan”, submission to which is the contemporary norm of pacification. From the perspective of radical terrorism, it is tyrannical. From other perspectives, it is open to criticism and change. Most importantly, it is on the side of rational arbitration rather than arbitrary ordeal. Even radical terrorism, which refuses to recognize the legitimacy of the abstract Leviathan, seeks to communicate its radical messages rather than to seek victory my means of physical annihilation of its opponents. (shrink)

The American Journal of Bioethics, Volume 12, Issue 3, Page 37-39, March 2012.

This paper explores the value of respect for personal autonomy in relation to clearly immoral and irrational acts committed freely and intentionally by competent people. Following Berlin's distinction between two kinds of liberty and Darwall's two kinds of respect, it is argued that coercive suppression of nonautonomous, irrational, and self-harming acts of competent persons is offensive to their human dignity, but not disrespectful of personal autonomy. Irrational and immoral choices made by competent people may claim only the negative liberty to (...) be left alone. Lives disposed to autonomy are worthy of solidarity and active support in addition to the right of free choice and action. Autonomous premeditated desires (distinguished from mere consent) may embody transcendental choices, which transcend consideration of physical and psychological well-being. Choices made by incompetent persons (e.g., children and the mentally disabled) are not related to autonomy, but to self-directedness. The value of human dignity confers protection to self-directedness, but not at the expense of other vital interests. (shrink)

:This article examines the concept of moral enhancement from two different perspectives. The first is a bottom-up approach, which aims at identifying fundamental moral traits and subcapacities as targets for enhancement. The second perspective, a top-down approach, is holistic and in line with virtue ethics. Both perspectives lead to the observation that alterations of material and social conditions are the most reliable means to improve prosocial behavior overall.Moral enhancement as a preventive measure invokes Gnostic narratives on the allegedly fallen status (...) of human nature, its search for salvation, and the dependence of the laity on heteronomous salvific interventions. The allure of the preventive kind of enhancement is attributable to its religious hues.Owing to the absence of clarity regarding moral enhancement and of metrics to evaluate its progress, humanity is at risk of prioritizing unclear and unsubstantiated measures of preventive diminishment at the expense of celebrating human capacities and joys. (shrink)

In the first part of this article we survey the concept of human rights from a philosophical perspective and especially in relation to the “right to healthcare”. It is argued that regardless of meta-ethical debates on the nature of rights, the ethos and language of moral deliberation associated with human rights is indispensable to any ethics that places the victim and the sufferer in its centre. In the second part we discuss the rise of the “right to privacy”, particularly in (...) the USA, as an attempt to make the element of personal free will dominate over the element of basic human interest within the structure of rights and when different rights seem to conflict. We conclude by discussing the relationship of human rights with moral values beyond the realm of rights, mainly human dignity, free will, human rationality and response to basic human needs. (shrink)

In dieser Arbeit werden drei Gedankenexperimente geprüft, die im Diskurs zur Moralität der Abtreibung vorgebracht wurden: der Geiger von Judith J. Thomson und zwei Erwiderungen darauf von Kenneth Himma und Christopher H. Conn. Sie sind dadurch charakterisiert, dass sie von Rechten sprechen, eine besondere Betonung auf Verkörperung legen und an die moralische Intuition appellieren. Ich behaupte, dass nur menschliche Individuen Menschenrechte haben können und dass Individuation nicht auf der Verletzung der moralischen Rechte anderer basieren kann. Deshalb kann der Fetus weder (...) Träger von moralischen Rechten noch ein Aggressor gegen die Rechte seiner Mutter sein. Die Paradigmen der Umweltethik scheinen für moralische Überlegungen über Abtreibung besser geeignet zu sein als das Paradigma der Rechte. Im Zentrum der Umweltethik stehen eher Fürsorge und Achtung vor dem Leben als Rechte; sie ist auf Verkörperung und natürliche Prozesse abgestimmt und beruft sich mehr auf Gefühle der Fürsorge und Tugend als auf ein Gerechtigkeitsgefühl. (shrink)

Although both codes of practice and virtue ethics are integral to the ethos and history of “medical professionalism”, the two trends appear mutually incompatible. Hence, in the first part of the paper we explore and explicate this apparent conflict and seek a direction for medical education. The theoretical and empirical literature indicates that moral deliberation may transcend the incompatibilities between the formal and the virtuous, may enhance moral and other aspects of personal sensitivity, may help design and improve other parts (...) of the curricula, and may foster self-awareness and clarification of the professional role. Not only are these goals essential for good and conscientious doctoring, but they may also reduce physicians’ “burn-out”. We argue that medical education should focus on the ubiquitous practice of deliberation in contemporary medicine, and especially the practice of moral deliberation. (shrink)

Foundational issues in statistical mechanics and the more general question of how probability is to be understood in the context of physical theories are both areas that have been neglected by philosophers of physics. This book fills an important gap in the literature by providing a most systematic study of how to interpret probabilistic assertions in the context of statistical mechanics. The book explores both subjectivist and objectivist accounts of probability, and takes full measure of work in the foundations of (...) probability theory, in statistical mechanics, and in mathematical theory. It will be of particular interest to philosophers of science, physicists and mathematicians interested in foundational issues, and also to historians of science. (shrink)

Advances in intracranial electroencephalography and neurophysiology have enabled the study of previously inaccessible brain regions with high fidelity temporal and spatial resolution. Studies of iEEG have revealed a rich neural code subserving healthy brain function and which fails in disease states. Machine learning, a form of artificial intelligence, is a modern tool that may be able to better decode complex neural signals and enhance interpretation of these data. To date, a number of publications have applied ML to iEEG, but clinician (...) awareness of these techniques and their relevance to neurosurgery, has been limited. The present work presents a review of existing applications of ML techniques in iEEG data, discusses the relative merits and limitations of the various approaches, and examines potential avenues for clinical translation in neurosurgery. One-hundred-seven articles examining artificial intelligence applications to iEEG were identified from 3 databases. Clinical applications of ML from these articles were categorized into 4 domains: i) seizure analysis, ii) motor tasks, iii) cognitive assessment, and iv) sleep staging. The review revealed that supervised algorithms were most commonly used across studies and often leveraged publicly available timeseries datasets. We conclude with recommendations for future work and potential clinical applications. (shrink)

Foundational issues in statistical mechanics and the more general question of how probability is to be understood in the context of physical theories are both areas that have been neglected by philosophers of physics. This book fills an important gap in the literature by providing a most systematic study of how to interpret probabilistic assertions in the context of statistical mechanics. The book explores both subjectivist and objectivist accounts of probability, and takes full measure of work in the foundations of (...) probability theory, in statistical mechanics, and in mathematical theory. It will be of particular interest to philosophers of science, physicists and mathematicians interested in foundational issues, and also to historians of science. (shrink)

We examine metonymy at psycho- and neurolinguistic levels, seeking to adjudicate between two possible processing implementations. We compare highly conventionalized systematic metonymy to lesser-conventionalized circumstantial metonymy. Whereas these two metonymy types differ in terms of contextual demands, they each reveal a similar dependency between the named and intended conceptual entities. We reason that if each metonymy yields a distinct processing time course and substantially non-overlapping preferential localization pattern, it would not only support a two-mechanism view but would suggest that conventionalization (...) acts as a linguistic categorizer. By contrast, a similar behavior in time course and localization would support a one-mechanism view and the inference that conventionalization acts instead as a modulator of contextual felicitousness, and that differences in interpretation introduced by conventionalization are of degree, not of kind. Results from three paradigms: self-paced reading, event-related potentials, and functional magnetic resonance imaging, reveal the following: no main effect by condition for either metonymy type immediately after the metonymy trigger, and a main effect for only the Circumstantial metonymy one word post-trigger ; a N400 effect across metonymy types and a late positivity for Circumstantial metonymy ; and a highly overlapping activation connecting the left ventrolateral prefrontal cortex and the left dorsolateral prefrontal cortex. Altogether, the pattern observed does not reach the threshold required to justify a two-mechanism system. Instead, the pattern is more naturally understood as resulting from the implementation of a generalized referential dependency mechanism, modulated by degree of context dependence/conventionalization, thus supporting architectures of language whereby “lexical” and “pragmatic” meaning relations are encoded along a cline of contextual underspecification. (shrink)

Resumen: Debido a varias razones históricas y realistas, el desarrollo de la teoríeorlsica de la mlsica en China se queda atrátrra cuanto al sistema de enseñanza, el contenido de la enseñanza y otros aspectos. Es una tarea importante para los trabajadores chinos de la misica revisar o complementar la teoríeorteorntar sica actual y los libros de texto relacionados, y luego construir un sistema de disciplina de la teoríeorla teordesica en China. Este artículo sintetiza las teoríeorreorr educacióducacirr las tehistoria de la (...) m sica, la cultura musical, la morfologíorfolog, la otras disciplinas relacionadas, utiliza valores científicos, objetivos y racionales y conceptos holísticos y comprensivos, toma el desarrollo de la educacióducaciedteoríeoracieducacsica de China como objeto de investigaciónvesttoma la historia como espejo para seguir considerando y prospectar la construccióonstrusistema de disciplina de la teoríeorla teordesica de China. Los fundamentos de la mtsica china pueden dividirse, a grandes rasgos, en tres periodos: (1) desde principios del siglo XX hasta la fundacióundacita la blica Popular China; (2) desde ese momento hasta el periodo de reforma y apertura; y (3) desde el periodo de reforma y apertura hasta la actualidad. La teoríeor teord. La teord. evolucionóvoluciond. La teord. Lfundacióundaciond. Lblica Popular China a travéravulun proceso de aceptaciócepasiva y absorcióbsactiva, como puede observarse en el desarrollo de la enseñanza de la teoríeorla teorde la ene lasica china y sus materiales didrcticos. La teoríeor teora teordidiales dpropagórprincipalmente desde el palacio a la iglesia, luego a las escuelas y finalmente a la sociedad. Como resultado, la enseñanza de la teoría musical china evolucionóvprogresivamente hacia un sistema menor mayor como modo dominante, y los fundamentos de la mtsica china se desviaron gradualmente. Tras el establecimiento de la Repiblica Popular China, la investigaciónvestigaciina, lprofundizado, lo que ha beneficiado el crecimiento de la disciplina de la teoríeorla teorbásica, que ahora se dirige hacia la diversificacióiversifprofundidad. El desarrollo de la teoríeorla teorde la teor teor de la tecontado con la ayuda de varios music musicusieducadores musicales de diversos campos académicos y puntos de vista de la investigaciónvestimodelo ideal de la construccióonstruccdisciplina de la teoríeorla teorde la teoconcibe sobre la base del principio de “combinar la historia con la teoríeor la tpeinar el desarrollo de la teoríeorla teordesica en China. Este modelo fomenta la integracióntegraciteoríeorgracirasica tradicional y la teoríeora teorlsica moderna desde una perspectiva diacrónica, refuerza la unidad del padel pal pmundo en la teoríeorla teorsica bcsica desde una perspectiva sincrónica, y presta atenciótenciiaconnotacióonnotacitecnología en su conjunto. (shrink)

While N6‐methyladenosine (m6A) is a well‐known epigenetic modification in bacterial DNA, it remained largely unstudied in eukaryotes. Recent studies have brought to fore its potential epigenetic role across diverse eukaryotes with biological consequences, which are distinct and possibly even opposite to the well‐studied 5‐methylcytosine mark. Adenine methyltransferases appear to have been independently acquired by eukaryotes on at least 13 occasions from prokaryotic restriction‐modification and counter‐restriction systems. On at least four to five instances, these methyltransferases were recruited as RNA methylases. Thus, (...) m6A marks in eukaryotic DNA and RNA might be more widespread and diversified than previously believed. Several m6A‐binding protein domains from prokaryotes were also acquired by eukaryotes, facilitating prediction of potential readers for these marks. Further, multiple lineages of the AlkB family of dioxygenases have been recruited as m6A demethylases. Although members of the TET/JBP family of dioxygenases have also been suggested to be m6A demethylases, this proposal needs more careful evaluation. (shrink)

This paper presents and discusses a recent Israeli proposal to legislate on the rights of the dying patient. A gap exists between elitist biases of the committee proposing the law, and popular values and sentiments. The proposed law divides the dying patients into two groups: “those who wish to go on living” and “those who wish to die”. The former will have a right to life prolonging extraordinary care. It is not clear who would foot the bill for this care. (...) Also it is hard to see how this munificence could fail to discriminate against all other patients. Both the secular ethicists and the rabbis involved in drawing up the proposal accepted the assumption that it is good for some terminal patients to die. The rabbis objected, however, to direct and active interventions that shorten life. The solution arrived at was to install timers in the ventilators so as to allow them to expire automatically unless the patient wishes for their resetting. (shrink)

As the capabilities of Artificial Intelligence (AI) have increased over recent years, so have the challenges of how to govern its usage. Consequently, prominent stakeholders across academia, government, industry, and civil society have called for states to devise and deploy principles, innovative policies, and best practices to regulate and oversee these increasingly powerful AI tools. Developing a robust AI governance system requires extensive collective efforts throughout the world. It also raises old questions of politics, democracy, and administration, but with the (...) new challenges posed by AI's growing influence on markets, governing structures, international relations, healthcare, science, and political activism. The Oxford Handbook of AI Governance delineates the scope of these issues and addresses the key questions of AI governance. Across forty-nine chapters, organized in nine major sections, the Handbook covers the theoretical and ethical foundations of AI governance, different frameworks for developing a governance structure for AI, practical perspectives on AI governance in different policy domains, economic analyses of AI governance, and concrete lessons about the impact of AI governance domestically and internationally. Chapter authors come from a wide set of disciplines, areas of study, and cultural backgrounds, providing a global perspective on AI governance. (shrink)

Success in online and blended courses requires engaging in self-regulated learning, especially for challenging STEM disciplines, such as physics. This involves students planning how they will navigate course assignments and activities, setting goals for completion, monitoring their progress and content understanding, and reflecting on how they completed each assignment. Based on Winne & Hadwin’s COPES model, SRL is a series of events that temporally unfold during learning, impacted by changing internal and external factors, such as goal orientation and content difficulty. (...) Thus, as goal orientation and content difficulty change throughout a course, so might students’ use of SRL processes. This paper studies how students’ SRL behavior and achievement goal orientation change over time in a large college introductory level physics course taught online. Students’ achievement goal orientation was measured by repeated administration of the achievement goals questionnaire-revised. Students’ SRL behavior was measured by analyzing their clickstream event traces interacting with online learning modules via a combination of trace clustering and process mining. Event traces were first divided into groups similar in nature using agglomerative clustering, with similarity between traces determined based on a set of derived characteristics most reflective of students’ SRL processes. We then generated causal nets for each cluster of traces via process mining and interpreted the underlying behavior and strategy of each causal net according to the COPES SRL framework. We then measured the frequency at which students adopted each causal net and assessed whether the adoption of different causal nets was associated with responses to the AGQ-R. By repeating the analysis for three sets of online learning modules assigned at the beginning, middle, and end of the semester, we examined how the frequency of each causal net changed over time, and how the change correlated with changes to the AGQ-R responses. Results have implications for measuring the temporal nature of SRL during online learning, as well as the factors impacting the use of SRL processes in an online physics course. Results also provide guidance for developing online instructional materials that foster effective SRL for students with different motivational profiles. (shrink)

We have investigated the nonlinear low-frequency microwave absorption of an ensemble of small metallic grains. Earlier Zhou et al. [Phys. Rev. Lett. 77, 1958 (1996)] have proved that linear absorption by such a system is due to a mesoscopic relaxation mechanism for which important contribution is from the grains with small level spacings between the ground state and the first excited state. Here we have shown further that such grains are anomalously sensitive to the field amplitude and the distribution of (...) level spacings. Since such a behavior depends on external magnetic field, we expect the appearance of a giant nonlinear magnetoresistance, as well as a very strong temperature dependence of the nonlinear microwave conductivity. (shrink)

Appearing in the “Cairo Declaration on Human Rights in Islam” as an undefined referent for the limits on freedom of expression in Islam, Shariah is still to be chased as an indefinable referent which restricts freedom of the expression in the Islamic Republic of Iran. Iran’s Press Law as well as Constitution unveil Shariah’s referent to be a person: the Jurist-Ruler around whom a cult of personality is legalized in terms of “Imamate” and around whom all the limits on freedom (...) of expression revolve. Interpretation of Shariah is not a solution but part of the problem in Iran. Such problem can be dealt in terms of three modes of self-expression which were invented by the Iranian Reformists to avoid self-censorship. The notion of master-signifier can be the key to unraveling the problem of self-referentiality in freedom of expression and its Reformist solution in Iran’s legal system. (shrink)

Parental decision making is necessary for contracting medical interventions that require personal risk–benefit evaluation, and for overseeing matters of education. In the nineteenth century, exemptions from obligatory vaccination were granted for religious and conscientious reasons. Then and today, religion and moral values play marginal roles in vaccine hesitancy and denialism. Rather, the key values invoked by vaccine hesitants and denialists are liberty and pluralism. Neither is compatible with limiting adolescents’ choice. Because vaccination does not require assessment of personal medical risks, (...) because it does not need to occur within the sphere of the doctor–patient relationship, and because the risk involved is within the range of their daily activities, adolescents have the right to free access to vaccination without legal requirement of parental involvement. Drawing on the development of Common Law, and on the development of respect for personal conscience in the history of ideas, this paper does not promote an argument that grants public health an overriding moral power. Rather, this paper rejects the presumption that vaccination of adolescents might involve a conflict between parental authority and public health. Free access to vaccination is compatible with the law and ethics of adolescents’ evolving autonomy in relation to healthcare. (shrink)