Epigenetic and transcriptional variability contribute to the vast diversity of cellular and organismal phenotypes and are key in human health and disease. In this review, we describe different types, sources, and determinants of epigenetic and transcriptional variability, enabling cells and organisms to adapt and evolve to a changing environment. We highlight the latest research and hypotheses on how chromatin structure and the epigenome influence gene expression variability. Further, we provide an overview of challenges in the analysis of biological variability. An (...) improved understanding of the molecular mechanisms underlying epigenetic and transcriptional variability, at both the intra- and inter-individual level, provides great opportunity for disease prevention, better therapeutic approaches, and personalized medicine. Epigenetic and transcriptional variability mediate phenotypic plasticity, enabling adaptation to changing environments. In this review, we describe the sources of inter- and intra-individual variability and discuss epigenetic regulators of gene expression variability, including DNA methylation and chromatin structure. Understanding these molecular mechanisms will improve therapeutic approaches and personalized medicine. (shrink)

Simone Weil (1909-1943) was a defining figure of the twentieth century; a philosopher, Christian, resistance fighter, anarchist, feminist, labor activist and teacher. She was described by T. S. Eliot as "a woman of genius, of a kind of genius akin to that of the saints," and by Albert Camus as "the only great spirit of our time." Originally published posthumously in two volumes, these newly reissued notebooks, are among the very few unedited personal writings of Weil's that still survive (...) today. Containing her thoughts on art, love, science, God and the meaning of life, they give context and meaning to Weil's famous works, revealing a unique philosophy in development and offering a rare private glimpse of her singular personality. (shrink)

Simone Weil is one of the most profound thinkers of the twentieth century. Her writings encompass an extraordinary breadth of subjects, including philosophy, religion, sociology, and politics. A political activist and resistance fighter, her accomplishments are even more astonishing in light of her death in 1943 at the age of thirty-four. Whilst Weil was concerned with deep philosophical questions - the nature of human thought and human faculties, the limits of language, and thought's contact with reality through mediation, science (...) and beauty - the full significance of her work has frequently been obscured by her categorization as a purely religious writer or Christian mystic. Simone Weil: Basic Writings is an expertly edited anthology of her most important writings, presenting Weil's philosophy as it relates to politics, the nature of work, human nature in its duality, necessity, beauty and goodness. D. K. Levy and Marina Barabas have translated all the extracts anew, including translations of important notes and references missing from existing English language editions of Weil's work. Following an extensive introduction by D. K. Levy which places Weil's life and thought in context, each section opens with a short introduction situating the chosen passages within Weil's oeuvre. Simone Weil: Basic Writings is an outstanding starting point for anyone seeking an introduction to Weil's philosophy, and also essential reading for students and scholars of Weil's thought in related disciplines. (shrink)

Into wrestling with that question, Simone Weil put the very substance of her mind and temperament.

"What is required if men and women are to feel at home in society and are to recover their vitality? Into wrestling with that question, Simone Weil put the very substance of her mind and temperament. The apparently solid edifices of our prepossessions fall down before her onslaught like ninepins, and she is as fertile and forthright in her positive suggestions . . . she can be relied upon to toss aside the superficial and to come to grips with (...) the essential and the profound." -- Time Literary Supplement. (shrink)

Gravity and Grace was the first ever publication by the remarkable thinker and activist, Simone Weil. In it Gustave Thibon, the priest to whom she had entrusted her notebooks before her untimely death, compiled in one remarkable volume a compendium of her writings that have become a source of spiritual guidance and wisdom for countless individuals.

Simone Weil's Leçons de Philosophie are derived from a course she taught at the lyce;e for girls at Roanne in 1933-4. Anne Reynaud-Gue;rithault was a pupil in the class; her notes are not a verbatim record but are a very full and, as far as one can judge, faithful rendering, often catching the unmistakable tone of Simone Weil's voice as well as the force and the directness of her thought. The lectures form a good general introduction to philosophy, (...) ranging widely over problems about perception, mind, language, reasoning and problems in moral and political philosophy too. Her method of presentation is a characteristic combination of abstract argument, personal experience and literary or historical reference. Peter Winch points out in his introduction to the book some of the more systematic connections in her philosophical work (and between this philosophical work and her other concerns), and makes a number of suggestive comparisons between Simone Weil and Wittgenstein. The translation is by Hugh Price from the Plon edition of 1959. Dr Price has added some notes to explain references in the text that might be unfamiliar to English speaking students beginning philosophy. (shrink)

自史蒂芬·霍金(Stephen Hawking) 的暢銷科普著作《時間簡史》(以下簡稱《簡史》) 在上世紀八十年代末問世以來，至今天二十一世紀，華人基督教界就他宇宙無起點的論述仍有相當之評論，但可惜對評論未有綜合分析。評論者因寫作目的，也甚少交代霍金宇宙學的來龍去脈。故本文嘗試略述霍金宇宙學的歷史 背景及發展經過，繼而舉出華人基督教界的評論，帶出其獨特性，並提出商確的地方，以反省未來可行路向。.

Research on the effects of perceptual manipulations on recognition memory has suggested that recollection is selectively influenced by task-relevant information and familiarity can be considered perceptually specific. The present experiment tested divergent assumptions that perceptual features can influence conscious object recollection via verbal code despite being task-irrelevant and that perceptual features do not influence object familiarity if study is verbal-conceptual. At study, subjects named objects and their presentation colour; this was followed by an old/new object recognition test. Event-related potentials showed (...) that a study-test manipulation of colour impacted selectively on the ERP effect associated with recollection, while a size manipulation showed no effect. It is concluded that verbal predicates generated at study are potent episodic memory agents that modulate recollection even if the recovered feature information is task-irrelevant and commonly found perceptual match effects on familiarity critically depend on perceptual processing at study. (shrink)

This thesis defends egalitarianism about knowledge and belief, on which neither is understood in terms of the other, from what I call the abductive argument. This argument is meant to favour views opposed to egalitarianism: doxasticism, on which knowledge is understood in terms of belief, and epistemicism, on which belief is understood in terms of knowledge. The abductive argument turns on the idea that doxasticism and epistemicism, by contrast with egalitarianism, explain certain data about knowledge and belief. I argue, however, (...) that no versions of doxasticism and epistemicism currently on offer are preferable to egalitarianism on abductive grounds. As part of my argument, I also defend the claim that knowledge, by contrast with belief, is an attitude to a fact and explore the implications of this claim for doxasticism and epistemicism. (shrink)

In Intimations of Christianity Among the Ancient Greeks , Simone Weil discusses precursors to Christian religious ideas which can be found in ancient Greek mythology, literature and philosophy. She looks at evidence of "Christian" feelings in Greek literature, notably in Electra, Orestes, and Antigone , and in the Iliad , going on to examine God in Plato, and divine love in creation, as seen by the ancient Greeks.

Encountering Derrida explores the points of engagement between Jacques Derrida and a host of other European thinkers, past and present, in order to counter recent claims that the era of deconstruction is finally drawing to a close. The book rereads Derrida in order to renew deconstruction's various conceptions of language, poetry, philosophy, institutions, difference and the future. This impressive collection of essays from the world's leading Derrida scholars re-evaluates Derrida's legacy and looks forward to the possible futures of deconstruction by (...) confronting various challenges to Derrida's thought. Collectively, the essays argue that Derrida must be read alongside others , an approach that produces some surprising new accounts of this challenging critical thinker. _ _. (shrink)

Philosophe politique et intellectuel engage dans la vie des idées aux Etats-Unis comme dans le monde, Michael Walzer est l'un des penseurs de la société parmi les plus stimulants a l'époque contemporaine. Son oeuvre défriche des pistes nouvelles de réflexion dans les domaines du politique, de la justice sociale, de la morale ou de l'identité culturelle. En même temps, Walzer, dont la pensée s'est forgée lors des luttes pour l'égalité des droits civiques aux USA et contre la guerre du Vietnam (...) dans les années 1960, poursuit une activité féconde d'animation du débat public à travers sa revue Dissent. Dans cet essai, Simon Wuhl a souhaité éclairer une autre dimension de la pensée de Michael Walzer : la relation étroite avec la pensée juive, dont les potentialités d'universalisation sont une référence majeure dans la plupart de ses écrits. Qu'elle s'exprime ouvertement comme dans son article emblématique sur " Les deux universalismes ", ou en arrière-fond comme dans son livre plus théorique sur les Sphères de justice, l'empreinte du judaïsme est toujours présente dans son oeuvre pour éclairer les grandes questions de société. Faisant par ailleurs retour, dans certains de ses travaux, sur les textes de base du judaïsme, Walzer mobilise les ressources méthodologiques des sciences humaines pour les soumettre à une relecture critique. (shrink)

Home births continue to constitute only a small percentage of all deliveries in the United States, in part because of concerns about their safety. While the literature is decidedly mixed in regard to the degree of risk, there are several studies that report that home birth may at times entail a small absolute increase in perinatal risks in circumstances that cannot always be anticipated prior to the onset of labor. While the definition of “small” will vary between individuals, and publications (...) vary in the level of risk they ascribe to birth at home, studies with the least methodological flaws and with adequate power often cite an excess death rate in the range of one per thousand.Home birth is, in that regard, but one example of patients’ choices and plans that sometimes carry increased risk or include alternatives that individual physicians feel uncomfortable supporting or recommending. Our intention in this opinion piece is not to advocate for or against home birth. Rather, we recognize that home birth is but one example of a patient choice that might differ from what a provider feels is in a woman’s best interests.In this article we will discuss ethical considerations in such circumstances using home birth as an example. We consider in this article how the ethical principles of respect for autonomy and non-maleficence can be balanced using, among other examples, the choice by some for a home birth. We discuss how absolute rather than relative risk should guide individuals’ evaluation of patient choices. We also consider how in some circumstances, the value and safety added by a physician’s participation may outweigh a potentially small increment in absolute risk that might result from a patient’s decision to deliver at home because of a perceived physician endorsement.We recognize, however, that doctors and midwives participating in choices they have not recommended, or may even believe will lead to or increase risk for adverse outcomes, presents dilemmas and raises important questions. When does respect for patient choice and autonomy become support for poor decision making? When is participation not respectful but enabling? Finally we discuss the role and responsibility of organized medicine in making all births as safe as possible. (shrink)

Is it tautological to call an action "wrongful discrimination?" Some philosophers and political theorists answer this question in the affirmative and claim that the term "discrimination" is intrinsically evaluative. Others agree that "discrimination" usually conveys the action’s moral wrongness but claim that the term can be used in a purely descriptive way. In this paper, we present two corpus studies and two experiments designed to test whether the folk concept of discrimination is evaluative. We demonstrate that the term has undergone (...) a historical development and is nowadays no longer used purely descriptively. Further, we show that this evaluation cannot be cancelled without yielding a contradiction. We conclude that the descriptive use of "discriminatory" is a thing of the past. (shrink)

ABSTRACTPeople often continue to rely on misinformation in their reasoning after they have acknowledged a retraction; this phenomenon is known as the continued-influence effect. Retractions can be particularly ineffective when the retracted misinformation is consistent with a pre-existing worldview. We investigated this effect in the context of depressive rumination. Given the prevalence of depressotypic worldviews in depressive rumination, we hypothesised that depressive rumination may affect the processing of retractions of valenced misinformation; specifically, we predicted that the retraction of negative misinformation (...) might be less effective in depressive ruminators. In two experiments, we found evidence against this hypothesis: in depressive ruminators, retractions of negative misinformation were at least as effective as they were in control participants, and more effective than retractions of positive misinformation. Findings are interpreted in terms of an attentional bias that may enhance the sali... (shrink)

Research on cognitive control has sparked increasing interest in recent years, as it is an important prerequisite for goal oriented human behavior. The paced auditory serial addition task has been used to test and train cognitive control functions. This adaptive, challenging task includes continuous performance feedback. Therefore, additional cognitive control capacities are required to process this information along with the already high task-load. The underlying neural mechanisms, however, are still unclear. To explore the neural signatures of the PASAT and particularly (...) the processing of distractive feedback information, feedback locked event-related potentials were derived from 24 healthy participants during an adaptive 2-back version of the PASAT. Larger neural activation after negative feedback was found for feedback related negativity, P300, and late positive potential. In early stages of feedback processing, a larger difference between positive and negative feedback responses was associated with poorer overall performance. This association was inverted in later stages. Together, our findings indicate stage-dependent associations between neural activation after negative information and cognitive functioning. Conceivably, increased early responses to negative feedback signify distraction, whereas higher activity at later stages reflects cognitive control processes to preserve ongoing performance. (shrink)

ABSTRACTFeelings and cognitions influence judgment through attribution. For instance, the attribution of positive feelings and cognitions to a stimulus leads to a positive judgment of that stimulus. We examined whether misattribution is moderated by the applicability of a distractor to the judgment question. For instance, when are people more likely to attribute to a target person the affective and cognitive experiences triggered by a kitten – when trying to judge the person’s cuteness or trustworthiness? The kitten triggers experiences specifically relevant (...) to cuteness, but people might more easily suspect the kitten’s potential influence when judging cuteness rather than trustworthiness. Using the Affect Misattribution Procedure, we found that applicability increases the effect of misattribution on valenced judgments. The results emphasise the importance of specific information in attribution and suggest that high applicability of distractors to the judgment question d... (shrink)

Although developmental dyslexia (DD) is frequently associate to a phonological deficit, the underlying neurobiological cause remain undetermined. One prominent hypothesis suggests a specific deficit in magnocellular-dorsal (M-D) pathway. Here we investigated the visual M-D and parvocellular-ventral (P-V) pathway in dyslexic and in chronological age and IQ-matched normally reading children by measuring dynamic (frequency doubling illusion) and static stimuli sensibility, respectively. A specific deficit in M-D task was found. Importantly, the M-D deficit was selectively shown in poor phonological decoders. M-D deficit (...) appears to be frequent because 75% of poor pseudo-word readers were at least 1 SD below the mean of the controls. Finally, a replication study by using a new group of poor phonological decoders and reading level controls suggests a possible role of M-D deficit in DD. These results showed that a M-D deficit might impair the sub-lexical mechanisms that are critical for reading development. The possible link between these findings and the oscillatory “temporal sampling” framework is discussed. (shrink)

Is consolidation needed to account for retroactive interference in free recall? Interfering mental activity during the retention interval of a memory task impairs performance, in particular if the interference occurs in temporal proximity to the encoding of the to-be-remembered information. There are at least two rival theoretical accounts of this temporal gradient of retroactive interference. The cognitive neuroscience literature has suggested neural consolidation is a pivotal factor determining item recall. According to this account, interfering activity interrupts consolidation processes that would (...) otherwise stabilize the memory representations of TBR items post-encoding. Temporal distinctiveness theory, by contrast, proposes that the retrievability of items depends on their isolation in psychological time. According to this theory, information processed after the encoding of TBR material will reduce the temporal distinctiveness of the TBR information. To test between these accounts, implementations of consolidation were added to the SIMPLE model of memory and learning. We report data from two experiments utilizing a two-list free recall paradigm. Modeling results imply that SIMPLE was able to model the data and did not benefit from the addition of consolidation. It is concluded that the temporal gradient of retroactive interference cannot be taken as evidence for memory consolidation. (shrink)

Is the brain really a computer? In particular, is our intelligence a computational achievement: is it because our brains are computers that we get on in the world as well as we do? In this paper I will evaluate an ambitious new argument to the contrary, developed in Landgrebe and Smith (2021a, 2022). Landgrebe and Smith begin with the fact that many dynamical systems in the world are difficult or impossible to model accurately (inter alia, because it is intractable to (...) find exact solutions to the differential equations that describe them—meaning we have to approximate—but at the same time they are such that small differences in starting conditions lead to big differences in final conditions, thwarting accurate approximation). Yet we manage to survive and thrive in a world full of such systems. Landgrebe and Smith argue from these premises that it is not because our brains are computers that we get on as well as we do: instead it is because of the various ways that we dynamically couple with such systems, these couplings themselves impossible to model well enough to emulate in silico. Landgrebe and Smith thus defend a dynamical systems model in the lineage of Gibson (1979), Van Gelder (1995), and Thompson (2007), though their focus is on decisively refuting the computationalist alternatives rather than developing the positive account. Here I will defend the claim that human intelligence is genuinely computational (and that whole brain emulation and others forms of AGI may be possible) against this argument. (shrink)

Although it is argued that social justice is a core concern for the discipline, nursing has not generally played a leadership role in the responses to many of the greatest social problems of our time. These include the accelerated rate of climate change, pandemic threats, systemic racism, growing health and social inequities, and the regulation of new technologies to ensure an equitable future ‘for all.’ In nursing codes of ethics, administration, education, policies, and practice, social justice is often claimed to (...) be a core value, yet it is rarely contextualized by philosophical or theoretical underpinnings. It appears that nurses’ commitment to social justice may stem more from a penchant for ‘doing good’ than an attempt to explore, understand, and enact what is meant by social justice from an ontological, epistemological, and methodological perspective. We contend that the dominance of a human science perspective in nursing contributes to a narrow definition of health and relegates many issues central to social justice to the margins of nurses’ care. In this article, we explore how the focus on ‘the human’ in the human science perspective may not only be limiting the capacity of nurses to develop strategies to adequately address social injustice, but in some instances, direct nurses to contribute to their very reproduction. We suggest that a critical interrogation of this human‐centric hegemony can identify avenues of rupture and introduce posthumanism as an additional philosophical perspective for consideration to help bridge the human‐social divide. (shrink)

BackgroundIn the early phase of the COVID-19 pandemic, many restrictions hit people in ways never seen before. Mental wellbeing was affected and burden was high, especially for high-risk groups such as parents. However, to our knowledge no research has yet examined whether being a parent was not only a risk for psychological burden but also a way to cope with the COVID-19 pandemic.MethodsAn online survey was used to collect data from 1,121 participants from April to June 2020. In addition to (...) demographic variables, risk factors and protective factors were collected. The dataset was divided into three groups: parents whose children lived at home, parents whose children did not live at home, and people who were not parents.ResultsA linear mixed effect model showed that parents had no higher burden than non-parents, and even less when children did not live at home. Expected risk factors were generally less important, and there were no differences between parents and non-parents. In contrast, parents had advantages in protective factors.ConclusionIn the early phase of the COVID-19 pandemic, it was shown that parents were not necessarily at risk due to additional burden, but also had prospects of coping better with the situation than people without children. (shrink)

That memory reconsolidation is the process underlying decisive, lasting therapeutic change has long been our proposal, and the recognition of its critical role by Lane et al. is a welcome development. However, in our view their account has significant errors due to neglect of research findings and neglect of previous work on the clinical application of those findings.

This chapter describes how philosophical theorizing about justice can be connected with empirical research in the social sciences. We begin by drawing on some received distinctions between ideal and non-ideal approaches to theorizing justice along several different dimensions, showing how non-ideal approaches are needed to address normative aspects of real-world problems and to provide practical guidance. We argue that there are advantages to a transitional approach to justice focusing on manifest injustices, including the fact that it enables us to set (...) aside some reasonable disagreements about justice. The ‘bottom-up’ approach we advocate, for which we borrow Wolff’s term ‘real-world political philosophy’, is an empirically-informed normative analysis that attends to specific, identifiable injustices, and thus is partial, though not isolationist. We illustrate our approach by considering how different models of the nature of disability suggest different kinds of remedy for injustices faced by persons living with disabilities. We reflect on the nature and significance of vulnerabilities, and we assess the role of public opinion in normative theorizing, suggesting a particular significance for the opinions and experiences of marginalized groups. We finally reflect on the relevance of European legal and institutional frameworks for theorizing justice in Europe. (shrink)

This study was designed to test three competing hypotheses (impaired configural processing; impaired Theory of Mind; atypical amygdala functioning) to explain the basic facial expression recognition profile of adults with autism spectrum disorders (ASD). In Experiment 1 the Ekman and Friesen (1976) series were presented upright and inverted. Individuals with ASD were significantly less accurate than controls at recognising upright facial expressions of fear, sadness and disgust and their pattern of errors suggested some configural processing difficulties. Impaired recognition of inverted (...) facial expressions suggested some additional difficulties processing the facial features. Unexpectedly, the clinical group misidentified fear as anger. In Experiment 2 feature processing of facial expressions was investigated by presenting stimuli in a piecemeal fashion, starting with either just the eyes or the mouth. Individuals with ASD were impaired at recognising fear from the eyes and disgust from the mouth; they also confused fearful eyes as being angry. The findings are discussed in terms of the three competing hypotheses tested. (shrink)

Este artículo intenta iluminar el problema de las traducciones de inscripciones árabes medievales durante el Barroco, en particular, las propuestas por Rodrigo Caro en 1643 de las inscripciones de Sevilla, traducciones primero ignoradas y luego consideradas, en el siglo XIX, como fraudulentas. Aquí se propone que estas falsas traducciones están condicionadas por el contexto de las de los Plomos del Sacromonte, por el ideal de la época de «antigüedad sagrada» y por el interés contrarreformista en ensalzar mártires y reliquias. Estos (...) eran todos elementos de un programa consciente de invención de un pasado cristiano, ficticio pero lleno de significado, en Andalucía. Los principales protagonistas de las traducciones de Sevilla, Rodrigo Caro, Pedro de Castro, Adán Centurión, estuvieron implicados en este proceso además de formar parte de una red, que implicaba a toda la península, de entusiastas anticuarios y falsarios. Su juicio crítico, cuando se enfrentaba con fraudes evidentes, quedaba obnubilado por su deseo de promover determinados fines religiosos y políticos. Sus traductores, que a menudo compartieron, era los productores de caprichosos instrumentos con que alcanzar dichos fines. (shrink)

The classic approaches -- Correspondence -- Coherence -- Pragmatism -- Deflationism -- Tarski and the semantic theory of truth -- Summary of part I -- Varieties of enquiry -- Truths of taste; truth in art -- Truth in ethics -- Reason -- Religion and truth -- Interpretations.

By examining an exemplar sample of mental health nursing educational policies and related legislation, in this article, we trace the discursive production of madness as an “othered” identity category. We engage in a critical discourse analysis of mental health nursing education in Canada, drawing on provincial and federal policies and legislation as the main sources of data. Theoretically framed by critical posthumanism and mad studies, this article outlines how the mad subjectivity becomes decontextualized out of its identity‐based understanding and recontextualized (...) as an inferior category of “the human,” circulating within discourses of pedagogy, economics, law, and psychiatry. The article maps the intertextual nexus of the discourse of mental health nursing education, making visible the complex, the arbitrary, and the sometimes‐contradictory nature of the discipline's grappling with identity‐based mental health concepts. We close with several implications for nursing policy, education, and practice. (shrink)

I show that frequentism, as an explanation of probability in classical statistical mechanics, can be extended in a natural way to a decoherent quantum history space, the analogue of a classical phase space. The result is a form of finite frequentism, in which Gibbs’ concept of an infinite ensemble of gases is replaced by the quantum state expressed as a superposition of a finite number of decohering microstates. It is a form of finite and actual frequentism (as opposed to hypothetical (...) frequentism) insofar as all the microstates exist, in keeping with the decoherence-based Everett interpretation, and some versions of pilot-wave theory. (shrink)

Is what's true ultimately relative to your point of view? So that what's true as viewed from over here might be false if viewed from over there? In this article, Simon Blackburn grapples with the suggestion that what's true is ultimately just a matter of perspective.

In their article “Three Kinds of Decision-Making Capacity for Refusing Medical Interventions,” Navin et al. (2022) argue that we should recognize two forms of decision-making capacity (DMC) besides...