Plasminogen activator inhibitor‐1 (PAI‐1) is a physiological inhibitor of urokinase (uPA), a serine protease known to promote cell migration and invasion. Intuitively, increased levels of PAI‐1 should be beneficial in downregulating uPA activity, particularly in cancer. By contrast, in vivo, increased levels of PAI‐1 are associated with a poor prognosis in breast cancer. This phenomenon is termed the “PAI‐1 paradox”. Many factors are responsible for the upregulation of PAI‐1 in the tumor microenvironment. We hypothesize that there is a breast cancer (...) predisposition to a more aggressive stage when PAI‐1 is upregulated as a consequence of Metabolic Syndrome (MetS). MetS exerts a detrimental effect on the breast tumor microenvironment that supports cancer invasion. People with MetS have an increased risk of coronary heart disease, stroke, peripheral vascular disease and hyperinsulinemia. Recently, MetS has also been identified as a risk factor for breast cancer. We hypothesize the existence of the “PAI‐1 cycle”. Sustained by MetS, adipocytokines alter PAI‐1 expression to promote angiogenesis, tumor‐cell migration and procoagulant microparticle formation from endothelial cells, which generates thrombin and further propagates PAI‐1 synthesis. All of these factors culminate in a chemotherapy‐resistant breast tumor microenvironment. The PAI‐1 cycle may partly explain the PAI‐1 paradox. In this hypothesis paper, we will discuss further how MetS upregulates PAI‐1 and how an increased level of PAI‐1 can be linked to a poor prognosis. BioEssays 29:1029–1038, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Objective To explore attitudes towards conscientious objections among medical students in the UK. Methods Medical students at St George's University of London, Cardiff University, King's College London and Leeds University were emailed a link to an anonymous online questionnaire, hosted by an online survey company. The questionnaire contained nine questions. A total of 733 medical students responded. Results Nearly half of the students in this survey stated that they believed in the right of doctors to conscientiously object to any procedure. (...) Demand for the right to conscientiously object is greater in Muslim medical students when compared with other groups of religious medical students. Discussion Abortion continues to be a contentious issue among medical students and this may contribute to the looming crisis in abortion services over the coming years. This project sheds some light on how future doctors view some of their ethical rights and obligations. Using empirical evidence, it reveals that conscientious objection is an issue in the UK medical student body today. These data could help anticipate problems that may arise when these medical students qualify and practise medicine in the community. Conclusion Clearer guidance is needed for medical students about the issue of conscientious objection at medical school. (shrink)

Based on a field study, this paper explores the differential role that perceived top management trustworthiness has on female and male employees’ negative emotions and turnover intentions in organizations. A theoretical model is established that explicates a negative indirect effect of perceived top management trustworthiness on employee turnover intentions through employee negative emotions. The results reveal that there is a negative relationship between perceived top management trustworthiness and employee negative emotions and resulting turnover intentions and that this effect is stronger (...) for female employees than for male employees. These results demonstrate the pivotal role played by top management trustworthiness, provide an explanation for the turnover gender gap, and highlight the subjectivity in reactions to trustworthiness perceptions. The implications for organizations are discussed in line with the need for top management to positively influence employees and particularly women, to retain them in their workforce. (shrink)

What might a theory of mental imagery look like, and how might one begin formulating such a theory? These are the central questions addressed in the present paper. The first section outlines the general research direction taken here and provides an overview of the empirical foundations of our theory of image representation and processing. Four issues are considered in succession, and the relevant results of experiments are presented and discussed. The second section begins with a discussion of the proper form (...) for a cognitive theory, and the distinction between a theory and a model is developed. Following this, the present theory and computer simulation model are introduced. This theory specifies the nature of the internal representations (data structures) and the processes that operate on them when one generates, inspects, or transforms mental images. In the third, concluding, section we consider three very different kinds of objections to the present research program, one hinging on the possibility of experimental artifacts in the data, and the others turning on metatheoretical commitments about the form of a cognitive theory. Finally, we discuss how one ought best to evaluate theories and models of the sort developed here. (shrink)

This study explored spatial navigation alongside several other cognitive abilities that are thought to share common underlying neurocognitive mechanisms (e.g., the capacity for self-projection, scene construction, or mental simulation), and which we hypothesised may be impaired in autism spectrum disorder (ASD). Twenty intellectually high-functioning children with ASD (with a mean age of ~8 years) were compared to 20 sex, age, IQ, and language ability matched typically developing children on a series of tasks to assess spatial navigation, episodic memory, episodic future (...) thinking (also known as episodic foresight or prospection), theory of mind, relational memory, and central coherence. This is the first study to explore these abilities concurrently within the same sample. Spatial navigation was assessed using the “memory island” task, which involves finding objects within a realistic, computer simulated, three-dimensional environment. Episodic memory and episodic future thinking were assessed using a past and future event description task. Theory of mind was assessed using the “animations” task, in which children were asked to describe the interactions between two animated triangles. Relational memory was assessed using a recognition task involving memory for items (line drawings), patterned backgrounds, or combinations of items and backgrounds. Central coherence was assessed by exploring differences in performance across segmented and unsegmented versions of block design. Children with ASD were found to show impairments in spatial navigation, episodic memory, episodic future thinking, and central coherence, but not theory of mind or relational memory. Among children with ASD, spatial navigation was found to be significantly negatively related to number of repetitive behaviours. In other words, children who showed more repetitive behaviours showed poorer spatial navigation. The theoretical and practical implications of the results are discussed. (shrink)

The aim of this paper is to explore how children learn to form new relationships with nature. It draws on a longitudinal case study of children participating in a stewardship project involving the conservation of salamanders during the school day in Stockholm, Sweden. The qualitative method includes two waves of data collection: when a group of 10-year-old children participated in the project (2015) and two years after they participated (2017). We conducted 49 interviews with children as well as using participant (...) observations and questionnaires. We found indications that children developed sympathy for salamanders and increased concern and care for nature, and that such relationships persisted two years after participation. Our rich qualitative data suggest that whole situations of sufficient unpredictability triggering free exploration of the area, direct sensory contact and significant experiences of interacting with a species were important for children’s development of affective relationships with the salamander species and with nature in an open-ended sense. Saving the lives of trapped animals enabled direct sensory interaction, feedback, increased understanding, and development of new skills for dynamically exploring further ways of saving species in an interactive process experienced as deeply meaningful, enjoyable and connecting. The behavioural setting instilled a sense of pride and commitment, and the high degree of responsibility given to the children while exploring the habitat during authentic situations enriched children’s enjoyment. The study has implications for the design of education programmes that aim to connect children with nature and for a child-sensitive urban policy that supports authentic nature situations in close spatial proximity to preschools and schools. (shrink)

Functional imaging studies of neurologically intact adults have demonstrated that the right posterior cerebellum is activated during verb generation, semantic processing, sentence processing, and verbal fluency. Studies of patients with cerebellar damage converge to show that the cerebellum supports sentence processing and verbal fluency. However, to date there are no patient studies that investigated the specific importance of the right posterior cerebellum in language processing, because: case studies presented patients with lesions affecting the anterior cerebellum, and group studies combined patients (...) with lesions to different cerebellar regions, without specifically reporting the effects of right posterior cerebellar damage. Here we investigated whether damage to the right posterior cerebellum is critical for sentence processing and verbal fluency in four patients with focal stroke damage to different parts of the right posterior cerebellum. We examined detailed lesion location by going beyond common anatomical definitions of cerebellar anatomy, and employed a recently proposed functional parcellation of the cerebellum. All four patients experienced language difficulties that persisted for at least a month after stroke but three performed in the normal range within a year. In contrast, one patient with more damage to lobule IX than the other patients had profound long-lasting impairments in the comprehension and repetition of sentences, and the production of spoken sentences during picture description. Spoken and written word comprehension and visual recognition memory were also impaired, however, verbal fluency was within the normal range, together with object naming, visual perception and verbal short-term memory. This is the first study to show that focal damage to the right posterior cerebellum leads to language difficulties after stroke; and that processing impairments persisted in the case with most damage to lobule IX. We discuss these results in relation to current theories of cerebellar contribution to language processing. Overall, our study highlights the need for longitudinal studies of language function in patients with focal damage to different cerebellar regions, with functional imaging to understand the mechanisms that support recovery. (shrink)

This commentary focuses on evidence from autism concerning the relation between metacognition and mindreading. We support Carruthers' rejection of models 1 (independent systems) and 3 (metacognition before mindreading), and provide evidence to strengthen his critique. However, we also present evidence from autism that we believe supports model 2 (one mechanism, two modes of access) over model 4 (mindreading is prior).

In 2001, France became one of the few countries to require corporate social responsibility reporting through its Nouvelles Régulations Économiques #2001-420. However, initial compliance with the statute was low, a factor implying the law lacked normativity. In this exploratory study, we attempt to determine whether there is movement toward normativity by examining the change in CSR disclosure from 2004 in comparison to 2010 for a sample of 81 publicly traded French firms. We measure both the space and the quality of (...) CSR disclosures, including in the latter a measure based on informational quality attributes as discussed by the International Accounting Standards Board, the Financial Accounting Standards Board, and the Global Reporting Initiative. We find significant increases in the space allocated to CSR disclosure, as well as some evidence of increased quality; although the informational quality of the disclosures remains quite low and fewer firms are including negative performance information in their reports. Finally, we document that differences in disclosure space and quality in 2004 appeared to be associated with legitimacy-based variables and that those relations remain largely unchanged in 2010. As such, it appears that the NRE’s goals of increased transparency remain unmet. (shrink)

Research highlights several risk and resilience factors at multiple ecological levels that influence individuals’ mental health and wellbeing in their everyday lives and, more specifically, in disaster or outbreak situations. However, there is limited research on the role of these factors in the early days of the COVID-19 crisis. The present study examined if and how potential risk factors and resilience factors are associated with mental health and well-being outcomes, and whether these resilience factors buffer the associations between risk factors (...) and said outcomes. One to two weeks after the government recommended preventative measures, 1,122 Canadian workers completed an online questionnaire, including multiple wellbeing outcome scales in addition to measures of potential risk and resilience factors. Structural equation models were tested, highlighting that overall, the considered risk factors were associated with poorer wellbeing outcomes, except social distancing which was associated with lower levels of stress. Each of the potential resilience factors was found to have a main effect on one or more of the wellbeing outcomes. Moderation analysis indicated that in general these resilience factors did not, however, buffer the risk factors. The findings confirm that the COVID-19 crisis encompasses several stressors related to the virus as well as to its impact on one’s social, occupational, and financial situation, which put people at risk for lower wellbeing as early as one to two weeks after the crisis began. While several resilience factors emerged as positively related to wellbeing, such factors may not be enough, or sufficiently activated at that time, to buffer the effects of the numerous life changes required by COVID-19. From an ecological perspective, while mental health professionals and public health decision-makers should offer/design services directly focused on mental health and wellbeing, it is important they go beyond celebrating individuals’ inner potential for resilience, and also support individuals in activating their environmental resources during a pandemic. (shrink)

This white paper outlines the plans of the History Philosophy Culture Working Group of the Next Generation Event Horizon Telescope Collaboration.

Legal battles continue in the UK over the Government’s plans to transport asylum seekers arriving on British shores to Rwanda in East Africa. Originally announced as a system for ‘processing’ asylum seekers, the Government has subsequently made it clear that there would not be an option for asylum seekers to return to the UK. The arrangement forms part of a deal between the UK and Rwanda, with the UK promising to invest £120 m in economic growth and development in Rwanda, (...) along with financing the cost of the ‘offshored’ asylum operation.1 The Government states that the policy is designed to break the business model of people traffickers involved in facilitating hazardous trips across the Channel in small, overcrowded and unseaworthy craft, leading to multiple drownings. Critics argue that the policy will do nothing to stop desperate people from seeking refuge in the UK, that transferring already traumatised people to Rwanda – which has been criticised for its human rights record – is inhumane and potentially outwith international law. Medical bodies, including the BMA, along with refugee organisations have expressed serious concerns about the health impact of such a system of ‘offshoring’. An equivalent system in Australia has been notorious for the devastating health impacts on those ‘offshored’ to the Pacific islands of Manus and Naura. Unusually in the UK the offshoring proposals have been greeted by unanimous condemnation by the Church of England. The lawfulness of the process is also subject to question. On the 14 July, a plane carrying a small number of asylum seekers to Rwanda was halted shortly before take-off following an intervention by the European Court of Human Rights. The ECtHR, part of the Council of Europe, of which the UK is still a member, said an Iraqi man known as KN faced ‘a real …. (shrink)

Sports are an excellent venue for demonstrating evolutionary principles to audiences not familiar with academic research. Team sports and sports fandom feature dynamics of in-group loyalty and intergroup competition, influenced by our evolved coalitional psychology. We predicted that reactions to expressions signaling mutual team/group allegiance would vary as a function of the territorial context. Reactions should become more prevalent, positive, and enthusiastic as one moves from the home territory to a contested area, and from a contested area to a rival’s (...) territory during active rival engagement. We also predicted that men would be more responsive than women based on sex differences in evolved coalitional psychology. The research team visited public places immediately prior to 2016–2017 collegiate football and basketball games. A male research confederate wore a sweatshirt displaying the logo of one of the competing university teams and vocalized the team’s most popular slogan when he saw a fan displaying similar logos. Observers followed 5 m behind, recording reactions and response positivity/enthusiasm. Reaction tone was most positive in the rival territory, least positive in the home territory, and intermediate in the periphery and contested territory. Rates of “no reaction” were lowest in the rival territory but were highest in the periphery. Men had higher reaction rates and more positive and enthusiastic reaction tones than women. Reactions generally followed predictions based on expected signal value. This project provides evidence that coalitional psychology influences dynamics related to university sports team rivalries and that context matters for expressions of alliance. (shrink)

My title is taken from the frontispiece to Ogilby's translation of Aesop ; since every Renaissance poet believed the statement to be true, let me start with my own example. John Denham's only play, The Sophy, published in August 1642, is a tale about the perils of jealousy. The good prince Mirza, after a miraculous victory over the Turks, returns in glory to his father's court, but leaves it shortly thereafter. In his absense, Haly, the evil courtier, follows a friend's (...) advice to " work on [the king's] fears, till fear hath made him cruel"1 and poisons the king's mind with jealousy against his son. Mirza returns only to be brutally blinded and killed, and the emperor soon dies stricken with remorse. Now it happens that Parliament justified all its actions in the months preceding the civil war on the grounds of the "fears and jealousies" that the king had inspired. Charles was incensed by the slogan and claimed angrily that he, if anyone, had the most cause for fears and jealousies.2 Denham obviously decided that here was the all-consuming topic around which a predominantly royalist drama could be written. He followed what I believe was the standard practice - the method that Fulke Greville said Sidney used and that Congreve repeated at the end of the century when he declared of The Double Dealer that "I design'd the Moral first, and to that Moral I invented the Fable."3 He found a plot in Thomas Herbert's Travels into Diverse Parts of Asia that recorded some terrible cruelties and catastrophes caused by jealousy, and he added the point that the emperor's mind had been wrought upon by his counselor. There is no evidence that the play was ever acted, but the most casual reader would have said to himself, "Yes, history reminds us that states destroy themselves through fears and jealousies, and we should abate our own before it is too late." · 1. Sir John Denham, The Poetical Works, ed. Theodore Howard Banks, 2d ed. , p.245. The references to fear and jealousy are so ubiquitous in the play that they need not be listed here.· 2. On March 1, 1642, in the angriest of his replies to Parliament so far, Charles exclaimed, "You speake of Jealousies and Feares: Lay your hands to your hearts, and aske your selves whether I may not likewise be disturbed with Feares and Jealousies: And if so, I assure you this Message hath nothing lessened them" . Although phrases like "distempers and jealousies" had been used earlier, Clarendon on two occasions is quite specific that "fears and jealousies" were "the new words which served to justify all indispositions and to excuse all disorders" in January 1642 . Taken with other evidence, Clarendon's remarks strongly suggest that The Sophy was written after Coopers Hill, and during seven months preceding its publication in August 1642.· 3. William Congreve, The Complete Plays, ed. Herbert Davis , p. 119. And compare John Donne in Sermons, ed. Evelyn M. Simpson are George R. Potter , 9:274: "All wayes of teaching are Rule and Example: and though ordinarily the Rule be first placed, yet the Rule it selfe is made of Examples...for, Example in matter of Doctrine, is as Assimiliation in matter of Nourishment; The Example makes that that is proposed for our learning and farther instruction, like something which we knew before, as Assimilation makes that meat, which we have received and digested, like those parts which are in our bodies before."John M. Wallace, author of Destiny His Choice: The Loyalism of Andrew Marvell and articles on Milton, Dryden Denham, Traherne, and Arnold, is professor of English at the University of Chicago. (shrink)