Over one hundred genes have been isolated from the human genome and shown to be causally related to specific human genetic diseases. Studies with gene‐specific probes have demonstrated that the mutations resulting in a particular phenotype are highly heterogeneous as a group, ranging from alterations in transcription or RNA processing in the nucleus, through to errors in mRNA translation in the cytoplasm. Even where the gene‐specific probe is not available, defects have been localized to chromosomal regions by family studies. Recently (...) developed methods for moving along the chromosome from a linked marker to the mutation are resulting in rapid advances in the understanding of many monogenic disorders. (shrink)

Humans, animals, and the environment face a universal crisis: antimicrobial resistance. Addressing AR and its multi-disciplinary causes across many sectors including in human and veterinary medicine remains underdeveloped. One barrier to AR efforts is an inconsistent process to incorporate the plenitude of stakeholders about what AR is and how to stifle its development and spread—especially stakeholders from the animal agriculture sector, one of the largest purchasers of antimicrobial drugs. In 2019, The Wellcome Trust released Reframing Resistance: How to communicate about (...) antimicrobial resistance effectively, which proposed the need to establish a consistent and harmonized messaging effort that describes the AR crisis and its global implications for health and wellbeing across all stakeholders. Yet, Reframing Resistance does not specifically engage the animal agriculture community. This study investigates the gap between two principles recommended by Reframing Resistance and animal agriculture stakeholders. For this analysis, the research group conducted 31 semi-structured interviews with a diverse group of United States animal agriculture stakeholders. Participants reported attitudes, beliefs, and practices about a variety of issues, including how they defined AR and what entities the AR crisis impacts most. Exploration of Reframing Resistance’s Principle 2, “explain the fundamentals succinctly” and Principle 3, “emphasis that this is universal issue; it can affect anyone, including you” reveals disagreement in both the fundamentals of AR and consensus of “who” the AR crisis impacts. Principle 2 may do better to acknowledge that animal agriculture stakeholders espouse a complex array of perspectives that cannot be summed up in a single perspective or principle. As a primary tool to combat AR, behavior change must be accomplished first through outreach to stakeholder groups and understanding their perspectives. (shrink)

The proliferation of personal data collection practices fundamentally reshapes how society is ordered and commercialized, and demands reconsideration of the possibilities for a just and equitable s...

People with higher levels of emotional intelligence (EI: adaptive emotional traits, skills and abilities) typically achieve more positive life outcomes, such as psychological wellbeing, educational attainment, and job-related success. Although the underpinning mechanisms linking EI with those outcomes are largely unknown, it has been suggested that EI may work as a ‘stress buffer’. Theoretically, when faced with a stressful situation, emotionally intelligent individuals should show a more adaptive response than those with low EI, such as reduced reactivity (less mood deterioration, (...) less physiological arousal), and faster recovery once the threat has passed. A growing number of studies have begun to investigate that hypothesis in respect to EI measured as both an ability (AEI) and trait (TEI), but results are unclear. To test the ‘stress-buffering’ function of EI, we systematically reviewed experimental studies that explored the relationship between both types of EI and acute stress reactivity or recovery. By searching 4 databases, we identified 45 eligible studies. Results showed that EI was only adaptive in certain contexts, and that findings differed according to stressor type, and how EI was measured. In terms of stress reactivity, TEI related to less mood deterioration during sports-based stressors (e.g. competitions), physical discomfort (e.g. dental procedure), and cognitive stressors (e.g. memory tasks), but did not appear as helpful in other contexts (e.g. speeches). Furthermore, effects of TEI on physiological stress responses, such as heart rate, were inconsistent. Effects of AEI on subjective and objective stress reactivity were often non-significant, with high levels detrimental in some cases. However, data suggest that both higher AEI and TEI relate to faster recovery from acute stress. In conclusion, results provide mixed support for the stress-buffering effect of EI. Limitations and quality of studies are also discussed. Findings could have implications for EI training programmes. (shrink)

The general conceit of Schiller’s aesthetic education is that our experiences with art and beauty set us free from internal and external constraints and allow us to embrace our full humanity as rational and sensuous beings. Experiencing the aesthetic, or the play impulse, puts one in a state of aesthetic determinacy—or rather indeterminacy—that Schiller calls the highest sense of freedom, aesthetic freedom. Gail K. Hart examines Anthony Burgess’s A Clockwork Orange as an example of what Schillerian aesthetic education might look (...) like in practice. Though it represents a distortion of Schiller’s aesthetic education, Hart argues that it also reveals an ineradicable element of coercion in aesthetic education. I argue that Burgess’s Ludovico Technique leaves out a key element of Schiller’s conception of aesthetic cultivation—play—and that Hart’s analysis of Schiller’s work likewise lacks a robust analysis of his notion of play. I argue that, when Schiller’s account of the play impulse is taken seriously as a necessary condition for aesthetic cultivation to take place, coercion is by definition made impossible. Aesthetic play is accomplished by the mutual destruction of physical and moral determinations, and this mutual erasure leads to a higher and more expansive freedom. External constraints and coercion cannot induce the aesthetic state, so aesthetic education as Schiller presents it in On the Aesthetic Education of Man cannot contain the element of coercion Hart suspects. (shrink)

PDZ (also called DHR or GLGF) domains are found in diverse membraneassociated proteins including members of the MAGUK family of guanylate kinase homologues, several protein phosphatases and kinases, neuronal nitric oxide synthase, and several dystrophin‐associated proteins, collectively known as syntrophins. Many PDZ domain‐containing proteins appear to be localised to highly specialised submembranous sites, suggesting their participation in cellular junction formation, receptor or channel clustering, and intracellular signalling events. PDZ domains of several MAGUKs interact with the C‐terminal polypeptides of a subset (...) of NMDA receptor subunits and/or with Shaker‐type K+ channels. Other PDZ domains have been shown to bind similar ligands of other transmembrane receptors. Recently, the crystal structures of PDZ domains, with and without ligand, have been determined. These demonstrate the mode of ligand‐binding and the structural bases for sequence conservation among diverse PDZ domains. (shrink)

What makes Don E. Scheid's article on indefinite detention interesting is that he thinks through many of the moral issues inherent in attempting to prevent certain k...

A fundamental cognitive function found across a wide range of species and necessary for survival is the ability to navigate complex environments. It has been suggested that mobility may play an important role in the development of spatial skills. Despite evolutionary arguments offering logical explanations for why sex/gender differences in spatial abilities and mobility might exist, thus far there has been limited sampling from nonindustrialized and subsistence-based societies. This lack of sampling diversity has left many unanswered questions regarding the effects (...) that environmental variation and cultural norms may have in shaping mobility patterns during childhood and the development of spatial competencies that may be associated with it. Here we examine variation in mobility, performance on large-scale spatial skills, and performance on small-scale spatial skills among Twa forager/pastoralist children whose daily lives have been dramatically altered since settlement and the introduction of government-funded boarding schools. Unlike in previous findings among Twa adults, boys and girls show similar patterns of travel on all measures of mobility. We also find no significant differences in spatial task performance by gender for large- or small-scale spatial skills. Further, children performed as well as adults did on mental rotation, and they outperformed adults on the water-level task. We discuss how children’s early learning environments may influence the development of both large- and small-scale spatial skills. (shrink)

K. E. Boxer explores moral responsibility, and whether it is compatible with causal determinism. She suggests that to answer this question we must focus on responsibility in the sense of liability, and that an incompatibilist view may only be preserved on an understanding of the moral desert of punishment that many find morally problematic.

In 1728, when the sixteen-year-old Hume, still apparently ‘at college’, was beginning, all unknown to his family, to turn his attention to philosophy, Edinburgh and Glasgow were swarming with earnest metaphysicians, many of them not much older than Hume himself. ‘It is well known’, the Ochtertyre papers relate, ‘that between the years 1723 and 1740 nothing was in more request with the Edinburgh literati, both laical and clerical, than metaphysical disquisitions’, and Locke, Clarke, Butler and Berkeley are mentioned as the (...) chief subjects for debate. Moreover, it is clear enough from the records that this surge of intellectual interests was chiefly the work of a younger generation, wearied alike of Calvinist theology and of Jacobite politics. Indeed to begin with it was the students’ societies which took the lead, and a plain enough hint of their serious critical attack is given in one sour entry in the diary of the Calvinist minister Woodrow for 1726. ‘These student clubs are like to have a very ill influence; they declare against reading and cry up thinking.’. (shrink)

In this paper I have tried to clarify the meaning of two very different sets of characteristics which philosophers have had in mind when they claimed that ethical terms were objective. I gave a very tentative answer to the question whether it is true to say that, in any of the distinguished senses, ethical statements are objective. Lastly, I indicated how the failure to make the distinction I draw was responsible for a number of confusions and unnecessary difficulties. More precisely, (...) in (1) I defined the first set of the characteristics in question, which together I have called solidity ; in (2) I give reasons why it is misleading to claim that ethical statements are solid and also misleading to claim they are not; in (3) I defined the second set of these characteristics, namely, proper contentiousness and proper complexity; in (4) I explained what I thought were the fundamental differences between these two sets of characteristics; in (5) I suggested that the solidity of an expression is normally a good reason for holding that the expression is properly contentious and properly complex; in (6) I claim that the failure to understand (4) and, therefore, also (5) leads to the following errors: (a) that, if an expression is solid , it must be properly contentious and properly complex ; that, if an expression is non-solid , it must be either properly contentious and properly simple , or properly non-contentious . (5) That, if an expression is properly contentious and properly complex , it must be solid ; if it is properly contentious and properly simple or if it is properly non-contentious , then it must be non-solid ; and lastly in (7) I have mentioned some common reasons for holding that ethical expressions have one or the other of the above-mentioned characteristics. (shrink)

Seeking to preserve electronically encoded evidence implies that an incident or event has occurred requiring fact extrapolation for presentation, as proof of an irregularity or illegal act. Whether target data are in transit or at rest, it is critical that measures be in place to prevent the sought information from being destroyed, corrupted or becoming unavailable for forensic investigation.

This essay uses a mental files theory of singular thought—a theory saying that singular thought about and reference to a particular object requires possession of a mental store of information taken to be about that object—to explain how we could have such thoughts about abstract mathematical objects. After showing why we should want an explanation of this I argue that none of three main contemporary mental files theories of singular thought—acquaintance theory, semantic instrumentalism, and semantic cognitivism—can give it. I argue (...) for two claims intended to advance our understanding of singular thought about mathematical abstracta. First, that the conditions for possession of a file for an abstract mathematical object are the same as the conditions for possessing a file for an object perceived in the past—namely, that the agent retains information about the object. Thus insofar as we are able to have memory-based files for objects perceived in the past, we ought to be able to have files for abstract mathematical objects too. Second, at least one recently articulated condition on a file’s being a device for singular thought—that it be capable of surviving a certain kind of change in the information it contains—can be satisfied by files for abstract mathematical objects. (shrink)

The Danish theologian-philosopher K. E. Løgstrup is second in reputation in his homeland only to Søren Kierkegaard. He is best known outside Europe for his _The Ethical Demand_, first published in Danish in 1956 and published in an expanded English translation in 1997. _Beyond the Ethical Demand_ contains excerpts, translated into English for the first time, from the numerous books and essays Løgstrup continued to write throughout his life. In the first essay, he engages the critical response to _The Ethical (...) Demand,_ clarifying, elaborating, or defending his original positions. In the next three essays, he extends his contention that human ethics “demands” that we are concerned for the other by introducing the crucial concept of “sovereign expressions of life.” Like Levinas, Løgstrup saw in the phenomenon of “the other” the ground for his ethics. In his later works he developed this concept of “the sovereign expressions of life,” spontaneous phenomena such as trust, mercy, and sincerity that are inherently other-regarding. The last two essays connect his ethics with political life. Interest in Løgstrup in the English-speaking academic community continues to grow, and these important original sources will be essential tools for scholars exploring the further implications of his ethics and phenomenology. “K. E. Løgstrup’s work undoubtedly made in his time an original contribution to the field of moral philosophy and philosophy of religion. This translation makes extracts from his later publications on moral philosophy accessible to an English-speaking audience. I am again impressed by the depth of his ideas, which are certainly not outdated and still relevant for contemporary debates in moral philosophy.” —_Bert Musschenga, Vrije Universiteit, Amsterdam _ “Making a large part of Knud Løgstrup’s legacy accessible to the English-speaking public is an event of enormous cultural, philosophical and political importance—and we are all in debt to his disciple, Kies van Kooten Niekerk, and the University Press of Notre Dame, for making it happen. Løgstrup, alongside few other giants of 20th Century ethical thought, like Emmanuel Levinas or Hans Jonas, anticipated and articulated all the major challenges and urgent tasks with which the coming century is likely to confront the moral self. Our ethical discourse was all the poorer so far for being barred access to his findings and proposition. This will no longer be the case.” —_Zygmunt Bauman, emeritus, University of Leeds_ “The publication of an English translation of Knut Eljert Løgstrup's later works in ethics provides a wider readership with the opportunity to better understand his important contribution to ethics in the second half of the last century. With his notion of the _Sovereign Expressions of Life_ Løgstrup articulates his rejection of moral atomism that has become influential in recent times. The introduction and annotation by Kees van Kooten Niekerk are very helpful to see how Løgstrup's thought developed beyond _The Ethical Demand.” —__Hans S. Reinders, Vrije Universiteit, Amsterdam_. (shrink)

Abstract:The experience of chronic pain can disrupt an understanding of oneself in terms of ability and possibility. In response, the pain sufferer needs an understanding conversation partner to help reinterpret their sense of self. Yet women in pain often encounter neglect, disbelief, or worse in today's medical institutions. They may end up seeking the authoritative pronouncement of a diagnosis rather than a partner in recovery. We must develop new language and new relationships within the medical field for helping women in (...) pain renegotiate their self-understanding and reinvigorate their engagement with the world and others through dialogue and play. (shrink)

Navigational performance responds to navigational challenges, and both decline with age in Western populations as older people become less mobile. But mobility does not decline everywhere; Tsimané forager-farmers in Bolivia remain highly mobile throughout adulthood, traveling frequently by foot and dugout canoe for subsistence and social visitation. We, therefore, measured both natural mobility and navigational performance in 305 Tsimané adults, to assess differences with age and to test whether greater mobility was related to better navigational performance across the lifespan. Daily (...) mobility was measured by GPS tracking, regional mobility through interview, navigational performance through pointing accuracy and perspective taking in environmental space, and mental rotation by a computerized task. Although mental rotation and spatial perspective taking declined with age, mobility and pointing accuracy remained high from mid-life through old age. Greater regional mobility was associated with greater accuracy at pointing and perspective taking, suggesting that spatial experience at environmental scales may help maintain navigational performance in later adulthood. (shrink)

A Correction to this paper has been published: https://doi.org/10.1007/s12110-021-09400-0.