Somatic mutations arising in human skin cancers are heterogeneously distributed across the genome, meaning that certain genomic regions (e.g., heterochromatin or transcription factor binding sites) have much higher mutation densities than others. Regional variations in mutation rates are typically not a consequence of selection, as the vast majority of somatic mutations in skin cancers are passenger mutations that do not promote cell growth or transformation. Instead, variations in DNA repair activity, due to chromatin organization and transcription factor binding, have been (...) proposed to be a primary driver of mutational heterogeneity in melanoma. However, as discussed in this review here, recent studies indicate that chromatin organization and transcription factor binding also significantly modulate the rate at which UV lesions form in DNA. The authors propose that local variations in lesion susceptibility may be an important driver of mutational hotspots in melanoma and other skin cancers, particularly at binding sites for ETS transcription factors. (shrink)

The stir caused in the civilised world by the writings of Bergson, particularly during the past decade, is evidenced by the volume of the stream of exposition and comment which has flowed and is still flowing. If the French were to be tempted to set up, after the German manner, a Bergson-Archiv they would be in no embarrassment for material, as the Appendix to this book - limited though it wisely is - will show. Mr. Gunn, undaunted by all this, (...) makes a further, useful contribution in his unassuming but workmanlike and well-documented account of the ideas of the distinguished French thinker. It is designed to serve as an introduction to Bergson's philosophy for those who are making their first approach to it, and as such it can be commended. (shrink)

At the beginning of 2020, COVID-19 became a global problem. Despite all the efforts to emphasize the relevance of preventive measures, not everyone adhered to them. Thus, learning more about the characteristics determining attitudinal and behavioral responses to the pandemic is crucial to improving future interventions. In this study, we applied machine learning on the multi-national data collected by the International Collaboration on the Social and Moral Psychology of COVID-19 (N = 51,404) to test the predictive efficacy of constructs from (...) social, moral, cognitive, and personality psychology, as well as socio-demographic factors, in the attitudinal and behavioral responses to the pandemic. The results point to several valuable insights. Internalized moral identity provided the most consistent predictive contribution—individuals perceiving moral traits as central to their self-concept reported higher adherence to preventive measures. Similar was found for morality as cooperation, symbolized moral identity, self-control, open-mindedness, collective narcissism, while the inverse relationship was evident for the endorsement of conspiracy theories. However, we also found a non-negligible variability in the explained variance and predictive contributions with respect to macro-level factors such as the pandemic stage or cultural region. Overall, the results underscore the importance of morality-related and contextual factors in understanding adherence to public health recommendations during the pandemic. (shrink)

: This paper represents the authors' attempt to provide a useful framework for discussing and investigating the links between the apparently disparate disciplines of neuroscience and dance. This attempt arose from an interdisciplinary course offering on this topic. A clear need apparent in preparing for an exploration of such uncharted territory was for some definition of the relevant landmarks in the form of a conceptual framework. The current status of that developing framework is presented here, as we consider the historical (...) context that contributed to the cultural distance between neuroscience and dance as disciplines; the conceptual and technical obstacles to collaborative work between these disciplines; and the recent developments, both conceptual and technological, that make the interface between neuroscience and dance a particularly fruitful source of inspiration not only for dancers and neuroscientists but potentially for a wide variety of disciplines touching on health and education in general. (shrink)

Objective Although patients exercise greater autonomy than in the past, and shared decision making is promoted as the preferred model for doctor-patient engagement, tensions still exist in clinical practice about the primary locus of decision-making authority for complex, scarce, and resource-intensive medical therapies: patients and their surrogates, or physicians. We assessed physicians’ attitudes toward decisional authority for adult venoarterial extracorporeal membrane oxygenation (VA-ECMO), hypothesizing they would favor a medical locus. Design, Setting, Participants A survey of resident/fellow physicians and internal medicine (...) attendings at an academic medical center, May to August 2013. Measurements We used a 24-item, internet-based survey assessing physician-respondents’ demographic characteristics, knowledge, and attitudes regarding decisional authority for adult VA-ECMO. Qualitative narratives were also collected. Main Results A total of 179 physicians completed the survey (15 percent response rate); 48 percent attendings and 52 percent residents/ fellows. Only 32 percent of the respondents indicated that a surrogate’s consent should be required to discontinue VA-ECMO; 56 percent felt that physicians should have the right to discontinue VA-ECMO over a surrogate’s objection. Those who self-reported as “knowledgeable” about VA-ECMO, compared to those who did not, more frequently replied that there should not be presumed consent for VA-ECMO (47.6 percent versus 33.3 percent, p = 0.007), that physicians should have the right to discontinue VAECMO over a surrogate’s objection (76.2 percent versus 50 percent, p = 0.02) and that, given its cost, the use of VA-ECMO should be restricted (81.0 percent versus 54.4 percent, p = 0.005). Conclusions Surveyed physicians, especially those who self-reported as knowledgeable about VA-ECMO and/or were specialists in pulmonary/ critical care, favored a medical locus of decisional authority for VA-ECMO. VA-ECMO is complex, and the data may (1) reflect physicians’ hesitance to cede authority to presumably less knowledgeable patients and surrogates, (2) stem from a stewardship of resources perspective, and/or (3) point to practical efforts to avoid futility and utility disputes. Whether these results indicate a more widespread reversion to paternalism or a more circumscribed usurping of decisional authority occasioned by VA-ECMO necessitates further study. (shrink)

It is difficult within the space of an article such as this to do more than indicate the principal features of Renouvier's philosophy, and it is, of course, impossible to give in detail a discussion of the immense wealth of thought and argument contained in his writings. Of his thought before 1854, the most important piece of work was the article on “Philosophie” written for the Encyclopédic Nouvelle. This in some respects shows his own thought developing in the direction.

In our contribution we will observe phenomenal architecture of a mind and operational architectonics of the brain and will show their intimate connectedness within a single integrated metastable continuum. The notion of operation of different complexity is the fundamental and central one in bridging the gap between brain and mind: it is precisely by means of this notion that it is possible to identify what at the same time belongs to the phenomenal conscious level and to the neurophysiological level of (...) brain activity organization, and what mediates between them. Implications for linguistic semantics, self-organized distributed computing algorithms, artificial machine consciousness, and diagnosis of dynamic brain diseases will be discussed briefly. (shrink)

This study employed a scenario-based approach whereby participants were asked to choose which communication channel they prefer in certain situations. The first aim was to determine the effect of the topic of interactions and social ties on channel choice. The second aim was to examine the underlying mechanisms in the relation between interaction topic and social ties and channel choice. A questionnaire was administered among 238 participants, who were presented five communication scenarios with topics of low and high intimacy and (...) four social ties, ranging from weak to strong. Results revealed that preference for face-to-face communication was highest, followed by audio-only computer-mediated communication and text-based CMC. Preference for FtF communication was higher when people valued feeling co-present and decreased when people valued feeling anonymous. Our results showed that communication channel choice is strategic and the choice for FtF ommunication, audio-only and text-based CMC largely depends on controllability, anonymity and co-presence. (shrink)

Context: Neurophenomenology is a relatively new field, with scope for novel and informative approaches to empirical questions about what structural parallels there are between neural activity and phenomenal experience. Problem: The overall aim is to present a method for examining possible correlations of neurodynamic and phenodynamic structures within the structurally-coupled work of Alexander Technique practitioners with their pupils. Method: This paper includes the development of an enkinaesthetic explanatory framework, an overview of the salient aspects of the Alexander Technique, (...) and the presentation of an elicitation interview technique as part of a neurophenomenological method. It will propose a way of testing the hypothesis that if, in the effective practice of Alexander Technique, there is a union between the nervous systems of teacher and pupil, it should be visible neurologically and affective phenomenologically, and thus it should be possible to investigate both its neural and phenomenal signatures. Results: The proposed means of testing the hypothesis is to use the elicitation interview technique alongside neural monitoring during the teaching of the Alexander Technique in four paired sets of subjects. Constructivist content: At the heart of this paper is the claim that all activity is co-activity. I make no assumption of an ontological primacy of mental or physical, or explanatory primacy of any methodology. Implications: This has important ramifications for somatic education and therapies, for establishing frameworks of co-engagement and care in health-care situations, and for understanding empathy. (shrink)

In this paper I explore the ways in which Alexander of Aphrodisias employs and develops so-called ‘common notions’ as reliable starting points of deductive arguments. He combines contemporary developments in the Stoic and Epicurean use of common notions with Aristotelian dialectic, and axioms. This more comprehensive concept of common notions can be extracted from Alexander’s commentary on Metaphysics A 1–2. Alexander puts Aristotle’s claim that ‘all human beings by nature desire to know’ in a larger deductive framework, (...) and adds weight to Aristotle’s use of the common understanding of the notion of ‘wisdom’. Finally I will indicate how these upgraded common notions are meant to play an important role in the general framework of metaphysics as a science. (shrink)

This book presents a comprehensive overview of what the criminal law would look like if organised around the principle that those who deserve punishment should receive punishment commensurate with, but no greater than, that which they deserve. Larry Alexander and Kimberly Kessler Ferzan argue that desert is a function of the actor's culpability, and that culpability is a function of the risks of harm to protected interests that the actor believes he is imposing and his reasons for acting in (...) the face of those risks. The authors deny that resultant harms, as well as unperceived risks, affect the actor's desert. They thus reject punishment for inadvertent negligence as well as for intentions or preparatory acts that are not risky. Alexander and Ferzan discuss the reasons for imposing risks that negate or mitigate culpability, the individuation of crimes, and omissions. (shrink)

This commentary explores biological models of analogical and associative learning in support of Illusion 1 and Illusion 4 in D. Noble’s target article. The intent is to support Noble’s theses of emergent higher level functionality from lower level stochastic dynamics and his etiological claim that “there is no privileged level of causation” through a biosemiotic lens. Upon these arguments, a case for creative agency via higher-dimensional constraints will also be made in support of Noble’s claim that organismic behavior is actively (...) directed by an agent. (shrink)

Throughout the 20th century, many doctors did not view pain management as an important aspect of their practice. Because pain cannot be objectively measured by the doctor, many doctors found it dif...

Achieving space situational awareness requires, at a minimum, the identification, characterization, and tracking of space objects. Leveraging the resultant space object data for purposes such as hostile threat assessment, object identification, and conjunction assessment presents major challenges. This is in part because in characterizing space objects we reference a variety of identifiers, components, subsystems, capabilities, vulnerabilities, origins, missions, orbital elements, patterns of life, operational processes, operational statuses, and so forth, which tend to be defined in highly heterogeneous and sometimes inconsistent (...) ways. The Space Domain Ontologies are designed to provide a consensus-based realist framework for formulating such characterizations in a way that is both consistent and computable. Space object data are aligned with classes and relations in a suite of ontologies built around the existing Space Object Ontology. They are stored in a dynamically updated Resource Description Framework triple store, which can be queried to support space situational awareness and the needs of spacecraft operators and analysts. This paper provides an overview of the Space Domain Ontologies and their development and use. It presents the motivation for and advantages of the Space Domain Ontologies, including the benefits they provide for enhancing and maintaining long-term space situational awareness. (shrink)

The posterior cortex, hippocampus, and prefrontal cortex in the Leabra architecture are specialized in terms of various neural parameters, and thus are predilections for learning and processing, but domain-general in terms of cognitive functions such as face recognition. Also, these areas are not encapsulated and violate Fodorian criteria for modularity. Anderson's terminology obscures these important points, but we applaud his overall message.

This collection of essays presents a novel interpretation of a signature work of Alexander of Aphrodisias, and of the Stoic philosophy he seeks to refute. It covers all chapters of the work, challenging existing scholarship in significant ways.

M. I. Finley in his Politics in the Ancient World , 92–6 has recently cast doubt on the extent to which religious phenomena were taken seriously in ancient times. We believe that in stressing the reasons for scepticism he has overlooked much positive evidence for the impact of religious scruples on political behaviour and that in generalising he has undervalued the differences in this respect between ancient societies. The significance of some of this positive evidence is admittedly uncertain since in (...) civilian life scruples might be easy to observe without great suffering. The acid test is in time of war, so that is the concern of our present enquiry. That attitudes varied can be shown only by comparing societies. We have here limited our discussion to three for which the evidence is well preserved: the world of the Greek city before Alexander the Great, Rome before Constantine, and the Jews in the Hellenistic and Roman period. Elucidation of the reasons for their distinct attitudes would reveal much about each of these societies and its religious practices and conceptions, but there will be space here only to show that considerable variety did indeed exist. Most ancient peoples assumed that their gods approved of war; the pacifism of some pre-Constantinian Christians was exceptional. Nor did such rules in combat as were observed necessarily have a religious foundation. Ancient like modern scruples were often based on moral and humanitarian grounds, as in the treatment of corpses and civilians; the gods, as the guardians of general morality, might be involved in such matters, but only at a remove. (shrink)

In this wide-ranging conversation, Michael Hardt reflects on recent transformations within Empire. Several unique themes emerge concerning power and pedagogy as they intersect with subjectivity and global crisis. Drawing on the common in conjunction with the tradition of love in education uncovers a different path that attends to today’s real political, ecological, and social needs. Finally, a focus on collectivity points to a possible strategy—collective intellectuality—for educators to revise traditional notions of leadership to encourage more ethical, democratic, and sustainable futures. (...) Yet, what this looks like in practice remains for us to imagine. (shrink)

Platonism has played a central role in Christianity and is essential to a deep understanding of the Christian theological tradition. At times, Platonism has constituted an essential philosophical and theological resource, furnishing Christianity with an intellectual framework that has played a key role in its early development, and in subsequent periods of renewal. Alternatively, it has been considered a compromising influence, conflicting with the faith's revelatory foundations and distorting its inherent message. In both cases the fundamental importance of Platonism, as (...) a force which Christianity defined itself by and against, is clear. Written by an international team of scholars, this landmark volume examines the history of Christian Platonism from antiquity to the present day, covers key concepts, and engages issues such as the environment, natural science and materialism. (shrink)

After over 300 years of scrutiny, the subject of Galileo continues to be pursued with unabating intensity. Dava Sobel's Galileo's Daughter points to the popular interest in the man and his legacy. The Catholic Church, understandably interested in dispelling the notion that its censure of Galileo centuries ago is proof positive that religious faith and science as well as ecclesiastical authority and free pursuit of scholarship are irreconcilable, continues to offer explanations. New books, articles and conferences probe both in breadth (...) and in depth the magnetic field charged by Galileo, science, and the Church. Galileo's analysis of the physics of motion has also received considerable attention. In particular, a great deal has been written during the past thirty years about the structure and objectives of three experiments with inclined planes. Galileo had carried them out in Padua and recorded them in his working papers. The assessments of the three experiments differ widely in points of detail, but all regard them as sophisticated, ingenious, and remarkable. This article presents a new critical study of these experiments. Its conclusion is that one of the experiments is indeed a success, but that the other two fail and are abandoned because Galileo did not have a firm enough grip on the underlying physical principles and mathematical relationships. (shrink)

Despite the frequency of stillbirths, the subsequent implications are overlooked and underappreciated. We present findings from comprehensive, systematic literature reviews, and new analyses of published and unpublished data, to establish the effect of stillbirth on parents, families, health-care providers, and societies worldwide. Data for direct costs of this event are sparse but suggest that a stillbirth needs more resources than a livebirth, both in the perinatal period and in additional surveillance during subsequent pregnancies. Indirect and intangible costs of stillbirth are (...) extensive and are usually met by families alone. This issue is particularly onerous for those with few resources. Negative effects, particularly on parental mental health, might be moderated by empathic attitudes of care providers and tailored interventions. The value of the baby, as well as the associated costs for parents, families, care providers, communities, and society, should be considered to prevent stillbirths and reduce associated morbidity. (shrink)

We report results of a study that utilizes a BCI to drive an interactive interface countermeasure that allows users to self-regulate sustained attention while performing an ecologically valid, long-duration business logistics task. An engagement index derived from EEG signals was used to drive the BCI while fNIRS measured hemodynamic activity for the duration of the task. Participants ( n = 30) were split into three groups (1) no countermeasures (NOCM), (2) continuous countermeasures (CCM), and (3) event synchronized, level-dependent countermeasures (ECM). (...) We hypothesized that the ability to self-regulate sustained attention through a neurofeedback mechanism would result in greater task engagement, decreased error rate and improved task performance. Data were analyzed by wavelet coherence analysis, statistical analysis, performance metrics and self-assessed cognitive workload via RAW-TLX. We found that when the BCI was used to deliver continuous interface countermeasures (CCM), task performance was moderately enhanced in terms of total 14,785 (σ = 423) and estimated missed sales 7.46% (σ = 1.76) when compared to the NOCM 14,529 (σ = 510), 9.79% (σ = 2.75), and the ECM 14,180 (σ = 875), 9.62% (σ = 4.91) groups. An “actions per minute” (APM) metric was used to determine interface interaction activity which showed that overall the CCM and ECM groups had a higher APM of 3.460 ( SE = 0.140) and 3.317 ( SE = 0.139) respectively when compared with the NOCM group 2.65 ( SE = 0.097). Statistical analysis showed a significant difference between ECM - NOCM and CCM - NOCM ( p p. (shrink)

We discuss two influential views of unification: mutual information unification (MIU) and common origin unification (COU). We propose a simple probabilistic measure for COU and compare it with Myrvold’s (2003, 2017) probabilistic measure for MIU. We then explore how well these two measures perform in simple causal settings. After highlighting several deficiencies, we propose causal constraints for both measures. A comparison with explanatory power shows that the causal version of COU is one step ahead in simple causal settings. However, slightly (...) increasing the complexity of the underlying causal structure shows that both measures can easily disagree with explanatory power. The upshot of this is that even sophisticated causally constrained measures for unification ultimately fail to track explanatory relevance. This shows that unification and explanation are not as closely related as many philosophers thought. (shrink)

Sender–receiver games, first introduced by David Lewis ([1969]), have received increased attention in recent years as a formal model for the emergence of communication. Skyrms ([2010]) showed that simple models of reinforcement learning often succeed in forming efficient, albeit not necessarily minimal, signalling systems for a large family of games. Later, Alexander et al. ([2012]) showed that reinforcement learning, combined with forgetting, frequently produced both efficient and minimal signalling systems. In this article, I define a ‘dynamic’ sender–receiver game in (...) which the state–action pairs are not held constant over time and show that neither of these two models of learning learn to signal in this environment. However, a model of reinforcement learning with discounting of the past does learn to signal; it also gives rise to the phenomenon of linguistic drift. 1 Introduction2 Dynamic Signalling Games with Reinforcement Learning2.1 Introducing new states2.2 Swapping state–action pairs3 Discounting the Past3.1 Learning to signal in a dynamic world3.2 An unexpected outcome: linguistic drift4 ConclusionAppendix: A Markov Chain Analysis. (shrink)

Individuals with Down syndrome (DS) are widely believed to possess considerable socialization strengths. However, the findings on social cognition capabilities are controversial. In the present study, we investigated whether individuals with DS exhibit shortage in face tuning, one of the indispensable components of social cognition. For this purpose, we implemented a recently developed Face-n-Food paradigm with food-plate images composed of food ingredients such as fruits and vegetables. The key benefit of such ‘face like non-face’ images is that single elements do (...) not facilitate face processing. In a spontaneous recognition task, 25 children with DS aged 9 to 18 years were presented with a set of Face-n-Food images bordering on the Giuseppe Arcimboldo style. The set of images was administered in a predetermined order from the least to most resembling a face. In DS individuals, thresholds for recognition of the Face-n-Food images as a face were drastically higher as compared not only with typically developing controls, but also with individuals with autistic spectrum disorders and Williams-Beuren syndrome. This outcome represents a significant step towards better conceptualization of visual social world in DS and neurodevelopmental disorders in general. (shrink)