Hedgehog (HH) signaling is a conserved pathway that drives developmental growth and is essential for the formation of most organs. The expression of HH target genes is regulated by a dual switch mechanism where GLI proteins function as bifunctional transcriptional activators (in the presence of HH signaling) and transcriptional repressors (in the absence of HH signaling). This results in a tight control of GLI target gene expression during rapidly changing levels of pathway activity. It has long been presumed that GLI (...) proteins also repress target genes prior to the initial expression of HH in a given tissue. This idea forms the basis for the limb bud pre‐patterning model for regulating digit number. Recent findings indicate that GLI repressor proteins are indeed present prior to HH signaling but contrary to this model, GLI proteins are inert as they do not regulate transcriptional responses or enhancer chromatin modifications at this time. These findings suggest that GLI transcriptional repressor activity is not a default state as assumed, but is itself regulated in an unknown fashion. We discuss these findings and their implications for understanding pre‐patterning, digit regulation, and HH‐driven disease. (shrink)

BackgroundPatients with COVID-19 may feel under pressure to participate in research during the pandemic. Safeguards to protect research participants include ethical guidelines [e.g. Declaration of Helsinki and good clinical practice (GCP)], legislation to protect participants’ privacy, research ethics committees (RECs) and informed consent. The International Committee of Medical Journal Editors (ICMJE) advises researchers to document compliance with these safeguards. Adherence to publication guidelines has been suboptimal in other specialty fields. The aim of this rapid review was to determine whether COVID-19 (...) human research publications report compliance with these ethical safeguards.MethodsA rapid systematic literature review was conducted in MEDLINE using the search term ‘COVID-19’. The search was performed in April 2020 with no start date and repeated to include articles published in November 2020. Filters were ‘Full free text available’ and ‘English Language’. Two reviewers assessed article title, abstracts and full texts. Non-COVID-19 articles and non-clinical studies were excluded. Independent reviewers conducted a second assessment of a random 20% of articles. The outcomes included reporting of compliance with the Declaration of Helsinki and GCP, REC approval, informed consent and participant privacy.ResultsThe searches yielded 1275 and 1942 articles of which 247 and 717 were deemed eligible, from the April search and November respectively. The majority of journals had editorial policies which purported to comply with ICMJE ethical standards. Reporting of compliance with ethical guidelines was low across all study types but was higher in the November search for case series and observational studies. Reporting of informed consent for case studies and observational studies was higher in the November search, but similar for case series. Overall, participant confidentiality was maintained but some case studies included a combination of details which would have enabled participant identification. Reporting of REC approval was higher in the November search for observational studies.ConclusionsWhile the majority of journal’s editorial policies purported to support the ethical safeguards, many COVID-19 clinical research publications identified in this rapid review lacked documentation of these important safeguards for research participants. In order to promote public trust, ethical declarations should be included consistently. (shrink)

Scholars have critiqued mainstream economic approaches to environmental valuation for decades. These critiques have intensified with the increased prominence of environmental valuation in decision-making. This paper has three goals. First, we summarise prominent critiques of monetary valuation, drawing mostly on the work of Clive Spash, who worked extensively on cost–benefit analysis early in his career and then became one of monetary valuation's most thorough and ardent critics. Second, we, as a group of scholars who study relational values, describe how relational (...) values research engages with and addresses many of the critiques of monetary valuation. Third, we offer suggestions for relational values research that continues and deepens its ability to respond to critiques of monetary valuation and contributes to transformative change towards sustainability. (shrink)

This study examines the public's and physicians' willingness to support deception of insurance companies in order to obtain necessary healthcare services and how this support varies based on perceptions of physicians' time pressures. Based on surveys of 700 prospective jurors and 1617 physicians, the public was more than twice as likely as physicians to sanction deception (26% versus 11%) and half as likely to believe that physicians have adequate time to appeal coverage decisions (22% versus 59%). The odds of public (...) support for deception compared to that of physicians rose from 2.48 to 4.64 after controlling for differences in time perception. These findings highlight the ethical challenge facing physicians and patients in balancing patient advocacy with honesty in the setting of limited societal resources. (shrink)

This article introduces a novel theoretical framework for psychopathy that bridges dominant affective and cognitive models. According to the proposed impaired integration (II) framework of psychopathic dysfunction, topographical irregularities and abnormalities in neural connectivity in psychopathy hinder the complex process of information integration. Central to the II theory is the notion that psychopathic individuals are “‘wired up’ differently” (Hare, Williamson, & Harpur, 1988, p. 87). Specific theoretical assumptions include decreased functioning of the Salience and Default Mode Networks, normal functioning in (...) executive control networks, and less coordination and flexible switching between networks. Following a review of dominant models of psychopathy, we introduce our II theory as a parsimonious account of behavioral and brain irregularities in psychopathy. The II theory provides a unified theoretical framework for understanding psychopathic dysfunction and integrates principle tenets of affective and cognitive perspectives. Moreover, it accommodates evidence regarding connectivity abnormalities in psychopathy through its network theoretical perspective. (shrink)

We present a novel semantic and conversational framework for a class of gradable-like constructions. These include metalinguistic comparatives, like "Ann is more a linguist than a philosopher", as well as metalinguistic equatives, degree modifications, and conditionals. To the extent previous literature discusses such metalinguistic gradability, the focus has been on comparatives. We extend our account of metalinguistic comparatives (Rudolph & Kocurek 2020) to cover a broader range of metalinguistic gradable constructions. On our semantic expressivist view, these all serve in various (...) ways to express speakers' relative commitments to different linguistic interpretations. (shrink)

This article contributes empirical findings and sociological theoretical perspectives to discussions of the role of community lay health workers, including in improving the health of individuals and communities. We focus on the role of the Health Trainer (HT), at its inception described as one of the most innovative developments in UK Public Health policy. As lay health workers, HTs are tasked with reducing health inequalities in disadvantaged communities by supporting clients to engage in healthier lifestyles. HTs are currently sociologically under-researched, (...) particularly in relation to occupational identity work, and the boundary work undertaken inter-occupationally with other health workers. To address this research lacuna, a qualitative study was undertaken with 25 HTs based in the Midlands region of the UK. In theorising our findings, we employ a novel combination of symbolic interactionist conceptualisation of 1) identity work, and of 2) boundary work. The article advances knowledge in the field of health and exercise by investigating and theorising how HTs construct, work at, manage, and communicate about professional/occupational boundaries, in order to provide personalised support to their clients in achieving and sustaining healthy behaviour change within the constraints of clients’ lifeworlds. (shrink)

This paper concludes a special feature of Sustainability Science that explores a broad range of social value theoretical traditions, such as religious studies, social psychology, indigenous knowledge, economics, sociology, and philosophy. We introduce a novel transdisciplinary conceptual framework that revolves around concepts of 'lenses' and 'tensions' to help navigate value diversity. First, we consider the notion of lenses: perspectives on value and valuation along diverse dimensions that describe what values focus on, how their sociality is envisioned, and what epistemic and (...) procedural assumptions are made. We characterise fourteen of such dimensions. This provides a foundation for exploration of seven areas of tension, between: (1) the values of individuals vs collectives; (2) values as discrete and held vs embedded and constructed; (3) value as static or changeable; (4) valuation as descriptive vs normative and transformative; (5) social vs relational values; (6) different rationalities and their relation to value integration; (7) degrees of acknowledgment of the role of power in navigating value conflicts. In doing so, we embrace the 'mess' of diversity, yet also provide a framework to organise this mess and support and encourage active transdisciplinary collaboration. We identify key research areas where such collaborations can be harnessed for sustainability transformation. Here it is crucial to understand how certain social value lenses are privileged over others and build capacity in decision-making for understanding and drawing on multiple value, epistemic and procedural lenses. (shrink)

This paper concludes a special feature of Sustainability Science that explores a broad range of social value theoretical traditions, such as religious studies, social psychology, indigenous knowledge, economics, sociology, and philosophy. We introduce a novel transdisciplinary conceptual framework that revolves around concepts of ‘lenses’ and ‘tensions’ to help navigate value diversity. First, we consider the notion of lenses: perspectives on value and valuation along diverse dimensions that describe what values focus on, how their sociality is envisioned, and what epistemic and (...) procedural assumptions are made. We characterise fourteen of such dimensions. This provides a foundation for exploration of seven areas of tension, between: (1) the values of individuals vs collectives; (2) values as discrete and held vs embedded and constructed; (3) value as static or changeable; (4) valuation as descriptive vs normative and transformative; (5) social vs relational values; (6) different rationalities and their relation to value integration; (7) degrees of acknowledgment of the role of power in navigating value conflicts. In doing so, we embrace the ‘mess’ of diversity, yet also provide a framework to organise this mess and support and encourage active transdisciplinary collaboration. We identify key research areas where such collaborations can be harnessed for sustainability transformation. Here it is crucial to understand how certain social value lenses are privileged over others and build capacity in decision-making for understanding and drawing on multiple value, epistemic and procedural lenses. (shrink)

We offer a novel account of metalinguistic comparatives, such as 'Al is more wise than clever'. On our view, metalinguistic comparatives express comparative commitments to conventions. Thus, 'Al is more wise than clever' expresses that the speaker has a stronger commitment to a convention on which Al is wise than to a convention on which she is clever. This view avoids problems facing previous approaches to metalinguistic comparatives. It also fits within a broader framework—independently motivated by metalinguistic negotiations and convention-shiftingexpressions— (...) that gives linguistic conventions a role in the semantics. (shrink)

Conventional wisdom has it that truth is always evaluated using our actual linguistic conventions, even when considering counterfactual scenarios in which different conventions are adopted. This principle has been invoked in a number of philosophical arguments, including Kripke’s defense of the necessity of identity and Lewy’s objection to modal conventionalism. But it is false. It fails in the presence of what Einheuser (2006) calls c-monsters, or convention-shifting expressions (on analogy with Kaplan’s monsters, or context-shifting expressions). We show that c-monsters naturally (...) arise in contexts, such as metalinguistic negotiations, where speakers entertain alternative conventions. We develop an expressivist theory—inspired by Barker (2002) and MacFarlane (2016) on vague predications and Einheuser (2006) on counterconventionals—to model these shifts in convention. Using this framework, we reassess the philosophical arguments that invoked the conventional wisdom. (shrink)

Global production networks connect multiple producers involved in fragmented manufacturing processes. Major brands and retailers, considered as lead firms, are under increasing pressure to ensure products made through GPNs are produced sustainably. Theories of governance developed to understand dynamics in outsourced production can provide insight into this issue. However, these theories and related empirical research have often focused on relationships between lead firms and upper-tier suppliers. When manufacturing involves multiple fragmented stages, understanding the role of lead firms becomes more difficult. (...) This article considers new governance roles that lead firms, as buyers, are playing when attempting to promote sustainable practices across all stages of production for buyer-driven industries. The focus is exploring the nature of new governance approaches which lead firms have developed in order to address diverse sustainability challenges found within GPNs, particularly related to lower-tier suppliers. These approaches can involve lead firms working through vertical buyer–seller links or developing new horizontal relationships, which link lead firms with lower-tier suppliers and governance processes in these suppliers’ local productive systems. The findings draw from field research examining how top UK garment retailers provide governance to producers involved in creating cotton garments in India and a review of publicised policies and practices of these retailers related to promoting sustainable production. Five types of governance mechanisms that can involve vertical or horizontal links are identified. Considering the growth of new governance relationships expands previous conceptions of the roles of lead firm governance. (shrink)

Despite the ever-changing field of artificial intelligence (AI) and its preponderance of pre-print articles, Cohen offers a timely, nuanced, and self-aware overview of ChatGPT and the world of Larg...

Background: Continuous viewing of ambiguous patterns is characterized by wavering perception that alternates between two or more equally valid visual solutions. However, when such patterns are viewed intermittently, either by repetitive presentation or by periodic closing of the eyes, perception can become locked or "frozen" in one configuration for several minutes at a time. One aspect of this stabilization is the possible existence of a perceptual memory that persists during periods in which the ambiguous stimulus is absent. Here, we use (...) a novel paradgim of temporally interleaved ambiguous stimuli to explore the nature of this memory, with particular regard to its potential impact on perceptual organization. Results: We found that the persistence of a perceptual configuration was robust to interposed visual patterns and, further, that at least three ambiguous patterns, when interleaved in time, could undergo parallel, stable time courses. Then, using an interleaved presentation paradigm, we established that the occasional reversal in one pattern could be coupled with that of its interleaved counterpart, and that this coupling was a function of the structural similarity between the patterns. Conclusions: We postulate that the stabilization observed with repetitive presentation of ambiguous patterns can be at least partially accounted for by processes that retain a recent perceptual interpretation, and we speculate that such memory may be important in natural vision. We further propose tha the interleaved paradigm introduced here may be of great value to gauge aspects of stimulus similarity that appeal to particular mechanisms of perceptual organization. (shrink)

A medical student's ability to present a case history is a critical skill that is difficult to teach. Case histories presented without theatrical engagement may fail to catch the attention of their intended recipients. More engaging presentations incorporate ‘stage presence’, eye contact, vocal inflection, interesting detail and succinct, well organised performances. They convey stories effectively without wasting time. To address the didactic challenge for instructing future doctors in how to ‘act’, the Mayo Medical School and The Mayo Clinic Center for (...) Humanities in Medicine partnered with the Guthrie Theater to pilot the programme ‘Telling the Patient's Story’. Guthrie teaching artists taught storytelling skills to medical students through improvisation, writing, movement and acting exercises. Mayo Clinic doctors participated and provided students with feedback on presentations and stories from their own experiences in patient care. The course's primary objective was to build students' confidence and expertise in storytelling. These skills were then applied to presenting cases and communicating with patients in a fresher, more engaging way. This paper outlines the instructional activities as aligned with course objectives. Progress was tracked by comparing pre-course and post-course surveys from the seven participating students. All agreed that the theatrical techniques were effective teaching methods. Moreover, this project can serve as an innovative model for how arts and humanities professionals can be incorporated for teaching and professional development initiatives at all levels of medical education. (shrink)

Ample sociological evidence demonstrates that binary gender ideologies are an intractable part of formal organizations and that transgender issues tend to be marginalized by a wide range of social institutions. Yet, in the last 15 years, more than 200 colleges and universities have attempted to ameliorate such realities by adopting gender-inclusive facilities in which students of any gender can share residential and restroom spaces. What cultural logics motivate these transformations? How can their emergence be reconciled with the difficulty of altering (...) the gender order? Using an original sample of 2,036 campus newspaper articles, I find that support for inclusive facilities frames such spaces as a resource through which an institution can claim improved standing in the field of higher education. This process of engendering reputation allows traditional gender separation in residential arrangements to be overcome, but it also situates institutional responsiveness to transgender issues as a means of enhancing a college or university’s public prestige. This, in turn, produces novel status systems in the field of higher education—albeit ones that perpetuate familiar forms of institutional and cultural exclusion. (shrink)

Introduction: Screen-based and mobile technology has grown at an unprecedented rate. However, little is understood about whether increased screen-use affects executive functioning, the range of mental processes that aid goal attainment and facilitate the selection of appropriate behaviors. To examine this, a systematic review was conducted.Method: This systematic review is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. A comprehensive literature search was conducted using Web of Science, MEDLINE, PsycINFO and Scopus databases to identify (...) articles published between 2007 and March 2020, examining the use of mobile technologies on aspects of EF in healthy adults aged 18–35 years. In total 6079 articles were screened by title, and 39 screened by full text. Eight eligible papers were identified for inclusion. Our methods were pre-registered on the PROSPERO international prospective register of systematic reviews.Results: A total of 438 participants were included across the eight studies. Five of the eight studies examined more than one EF. Five studies measured inhibition, and four studies measured decision-making. Smartphone use was negatively associated with inhibition and decision-making. Working memory performance was found to be improved by increased time engaging in video games and by refraining from smartphone use prior to bedtime. Quality assessments indicated high risk of methodological biases across the studies and a low quality of evidence for determining the relationship between technology use and executive functioning.Conclusions: This review highlights the scarcity of the literature in this area. It presents a call for rigorous and objective research to further our understanding of the impact of mobile technology on different aspects of executive function. (shrink)

Moutoussis, K., A. Maier, S. Zeki and N. K. Logothetis: Seeing invisible motion: responses of area V5 neurons in the awake-behaving macaque. Soc. for Neurosci. Abstr. 390.11, 1.

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)

How can we provide the best care for the growing population of older adults, many of whom are either very frail or very sick? The traditional medical model of care is focused on treatment of single diseases. This can work well for pneumonia, cancer, or diabetes in younger patients. It does not, however, work as well for frail older adults who have accumulated multiple chronic conditions and disabilities. These elders often depend on family or paid caregivers to provide assistance with (...) taking medications, transportation, and other activities of daily living, such as dressing and bathing. A practitioner in the traditional medical model might prescribe medications that make sense in isolation but have harmful... (shrink)

I was in manufacturing for over thirty years and a manager for nearly twenty-five. During that time it never occurred to me that the consequentialist, utilitarian framework I used was inadequate as a conceptual framework for making decisions to ensure organisational viability and success.1 The framework gave three criteria which enabled me to construct a rational approach to issues associated with my role as a manager: To show that this framework is adequate as a basis for managerial decision making I (...) want to spell out the logical implications of the three criteria and show that they are necessary and jointly sufficient to provide an epistemically sound framework for managerial decisions. I will argue that we can look to managerial practice for examples which can serve as paradigms for constructing a pragmatic approach to management decision making, one that — when employed correctly — will result in the best moral outcome for all those affected by a decision.2 This approach is derived from, and ultimately justified by, the primary role responsibility of a manager to create and implement a healthy work environment. This is one designed to be viable so that the organisation can compete successfully in the marketplace and meet the morally minimal standard that we ought not to cause unnecessary and avoidable harm to innocent people. Because the approach is goal directed, it is teleological and consequential in nature. I maintain that a workplace, or organisation, is healthy when all the components that constitute it are working coherently together to achieve legitimate organisational goals designed to ensure the best chances of being viable and competitive. Such an organisation is what I term optimally functional.3. (shrink)

Socrates' aim in the Republic is to show that being just is crucial for happiness. In Republic IV, Socrates argues that the just individual is one in whom each part of the soul or psyche performs its proper function, with the result that the individual attains psychic harmony. Commentators have worried, however, that this account of what it is to be just has little to do with being just in the ordinary sense of the term, which involves acting with regard (...) for the good of others. In this essay, I describe three attempts to show that there is a connection between Socrates' account of justice and justice in the ordinary sense of the term and I raise criticisms of each. I then outline my own approach, which emphasizes the importance of good relations with others for happiness. (shrink)

The medium of payment typically is defined as that which is generally accepted in payment for goods and services or in the settlement of debt. Perhaps because modern monetary systems function so well in providing media of payment, we seldom consider the question of why they enjoy the general acceptability by which they are identified. Yet, because monetary systems evolve and change, such basic questions warrant occasional re-examination to ensure that contemporary analysis does not, unwittingly, embody and foster the errors (...) of an earlier time. (shrink)

The paper describes two practical exercises (and their learning outcomes) requiring students to consider certain concrete decisions made by managers in business and professional life. The first exercise requires students to consider that competitive economic exchange inevitably puts managers in situations where they cannot accurately predict the outcomes of their decisions, and often results in harm to innocent people. In this practical exercise, seven discussion situations are described and students are asked to make decisions that take into account the individuals (...) affected by these managerial decisions. Students are asked to consider various ethical theories and devise creative solutions so as to avoid unnecessary harm. The second exercise places students in roles that represent shareholders and stakeholders and asks them to consider the relocation of a manufacturing company to their community. (shrink)

Western societies today are coming unmoored in the face of an earth-shaking ethical and cultural paradigm shift. At its core is the question of what it means to be human and how we are meant to live. The old answers are no longer accepted; a dizzying array of options are offered in their stead. Underpinning this smorgasbord of lifestyles is a thicket of unquestioned assumptions, such as the separation of gender from biological sex, which not so long ago would have (...) been universally rejected as radical notions. In the spring of 2019, a group of Orthodox Christian scholars drawn from a wide variety of academic disciplines met together to offer responses to the moral crisis our generation faces, elaborating upon its various forms and facilitating a fuller understanding of some of its theological and philosophical foundations. In doing so they offer support to all those who question the claims that are so forcefully insisted upon today--a clarity that will aid them in standing up and resisting trends that have already shown to be the cause of great suffering and unhappiness. (shrink)