How epigenetic mechanisms regulate genome output and response to stimuli is a fundamental question in development and disease. Past decades have made tremendous progress in deciphering the regulatory relationships involved by correlating aggregated (epi)genomics profiles with global perturbations. However, the recent development of epigenetic editing technologies now enables researchers to move beyond inferred conclusions, towards explicit causal reasoning, through 'programing’ precise chromatin perturbations in single cells. Here, we first discuss the major unresolved questions in the epigenetics field that can be (...) addressed by programable epigenome editing, including the context‐dependent function and memory of chromatin states. We then describe the epigenetic editing toolkit focusing on CRISPR‐based technologies, and highlight its achievements, drawbacks and promise. Finally, we consider the potential future application of epigenetic editing to the study and treatment of specific disease conditions. (shrink)

Formation of branching epithelial trees from unbranched precursors is a common process in animal organogenesis. In humans, for example, this process gives rise to the airways of the lungs, the urine‐collecting ducts of the kidneys and the excretory epithelia of the mammary, prostate and salivary glands. Branching in these different organs, and in different animal classes and phyla, is morphologically similar enough to suggest that they might use a conserved developmental programme, while being dissimilar enough not to make it obviously (...) certain that they do. In this article, I review recent discoveries about the molecular regulation of branching morphogenesis in the best‐studied systems, and present evidence for and against the idea of there being a highly conserved mechanism. Overall, I come to the tentative conclusion that key mechanisms are highly conserved, at least within vertebrates, but acknowledge that more work needs to be done before the case is proved beyond reasonable doubt. BioEssays 24:937–948, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Epithelia can be defined morphologically as tissues that line surfaces, and ultrastructurally with reference to their cells' apico‐basal polarity and possession of specific cell‐cell junctions. Defining the epithelial phenotype at a molecular level is more problematic ‐ while it is easy to name proteins (e.g. keratins) expressed by a “typical” epithelium, no known molecules are expressed by every epithelium but by no other tissues. Cells can differentiate to and from the epithelial state as part of normal development, as a response (...) to disease or when manipulated in culture. Many factors (matrix components, adhesion molecules, growth factors, transcription factors) have been identified that can trigger these transitions of phenotype in specific cases, but to date no general master regulators of the epithelial state have been found. The epithelial state may therefore be controlled by multiple regulatory genes so that there is no single molecule responsible for all of the diverse types of epithelium that exist in higher animals. (shrink)

Prior research shows that reasoners' confidence is poorly calibrated (Shynkaruk & Thompson, 2006). The goal of the current experiment was to increase calibration in syllogistic reasoning by training reasoners on (a) the concept of logical necessity and (b) the idea that more than one representation of the premises may be possible. Training improved accuracy and was also effective in remedying some systematic misunderstandings about the task: those in the training condition were better at estimating their overall performance than those who (...) were untrained. However, training was less successful in helping reasoners to discriminate which items are most likely to cause them difficulties. In addition we explored other variables that may affect confidence and accuracy, such as the number of models required to represent the problem and whether or not the presented conclusion was necessitated by the premises, possible given the premises, or impossible given the premises. These variables had systematically different relationships to confidence and accuracy. Thus, we propose that confidence in reasoning judgements is analogous to confidence in memory retrievals, in that they are inferentially derived from cues that are not diagnostic in terms of accuracy. (shrink)

Since the growth cone was first described a century ago by Cajal, considerable effort has been directed towards understanding the mechanisms responsible for its guidance. Traditionally, attention has focussed on the role of adhesive molecules in determining neural development. Recently, it has become apparent that inhibitory interactions may play a crucial part in axonal navigation. A common feature of inhibition seen in three model systems (peripheral nerve segmentation, retinotectal mapping and CNS/PNS segregation) is a collapse of the motile structures of (...) the growth cone. It is increasingly clear that the identification of molecular mechanisms of inhibition, as well as those of adhesion, will be of fundamental importance to understanding neural development. (shrink)

Focusing on the body as a visual and discursive platform across public space, this book explores marginalization as a sociocultural practice and hegemonic schema. The chapters center upon physical contexts, discursive spaces, and philosophical arenas to deconstruct seemingly intrinsic connections between body and behavior, whiteness, and normativity.

Although widely studied in other domains, relatively little is known about the metacognitive processes that monitor and control behaviour during reasoning and decision-making. In this paper, we examined the conditions under which two fluency cues are used to monitor initial reasoning: answer fluency, or the speed with which the initial, intuitive answer is produced, and perceptual fluency, or the ease with which problems can be read. The first two experiments demonstrated that answer fluency reliably predicted Feeling of Rightness judgments to (...) conditional inferences and base rate problems, which subsequently predicted the amount of deliberate processing as measured by thinking time and answer changes; answer fluency also predicted retrospective confidence judgments. Moreover, the effect of answer fluency on reasoning was independent from the effect of perceptual fluency, establishing that these are empirically independent constructs. In five experiments with a variety of reasoning problems similar to those of Alter et al., we found no effect of perceptual fluency on FOR, retrospective confidence or accuracy; however, we did observe that participants spent more time thinking about hard to read stimuli, although this additional time did not result in answer changes. In our final two experiments, we found that perceptual disfluency increased accuracy on the CRT, but only amongst participants of high cognitive ability. As Alter et al.’s samples were gathered from prestigious universities, collectively, the data to this point suggest that perceptual fluency prompts additional processing in general, but this processing may results in higher accuracy only for the most cognitively able. (shrink)

Branching morphogenesis of epithelia is an important mechanism in mammalian development. The last decade has seen the identification of many signalling pathways and intracellular mechanisms that control epithelial branching. Tissue‐level mechanisms that space new branches out have, however, remained an unsolved problem. A recent publication by Nelson et al.1 suggests—if extrapolation from their novel and abstract culture system is valid—that branches may be spaced out by a system of mutual inhibition based on diffusion of TGFβ. Such a system would allow (...) a developing tree to arrange itself, without detailed genetic specification, by adaptive self‐organization. BioEssays 29: 205–207, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Two studies examined the use of think aloud (TA) protocol as a means for collecting data of cognitive processes during performance in golf. In study 1, TA was employed to examine if different verbalisation (Level 2 or Level 3 TA) instructions influence performance of high and low skilled golfers. Participants performed 30 putts using TA at either Level 2, Level 3, or no verbalization condition. Although Level 3 verbalization produced a higher volume of verbal data than Level 2, TA at (...) either level 2 or 3 did not impair putting performance compared to no verbalization. Study 2 examined the congruence between data collected via TA at Level 3 and cued retrospective recall of cognitive processes during golf performance. Experienced golfers performed six holes of golf whilst engaging in Level 3 TA. After performance, three semi-structured retrospective interviews were conducted (ten minutes after performance, 24 hours after performance and 48 hours after performance). A comparison of the themes identified large discrepancies between the information reported during TA and at interview, with only 38-41% similarity in variables reported to influence decision making on each hole. Both studies suggest TA is a valuable method for recording cognitive processes of individuals during task performance. TA provides richer verbal data regarding decisions than cued retrospective recall, and TA does not negatively impact performance. (shrink)

There is now a rapidly expanding population of interlinked developmental biology databases on the World Wide Web that can be readily accessed from a desk‐top PC using programs such as Netscape or Mosaic. These databases cover popular organisms (Arabidopsis, Caenorhabditis, Drosophila, zebrafish, mouse, etc.) and include gene and protein sequences, lists of mutants, information on resources and techniques, and teaching aids. More complex are databases relating domains of gene expression to embryonic anatomy and these range from existing text‐based systems for (...) specific organs such as kidney, to a massive project under development, that will cover gene expression during the whole of mouse embryogenesis. In this brief article, we review selected examples of databases currently available, look forward to what will be available soon, and explain how to gain access to the World Wide Web. (shrink)

Name der Zeitschrift: Semiotica Jahrgang: 2014 Heft: 202 Seiten: 41-79.

In this reply, we provide an analysis of Alter et al. response to our earlier paper. In that paper, we reported difficulty in replicating Alter, Oppenheimer, Epley, and Eyre’s main finding, namely that a sense of disfluency produced by making stimuli difficult to perceive, increased accuracy on a variety of reasoning tasks. Alter, Oppenheimer, and Epley argue that we misunderstood the meaning of accuracy on these tasks, a claim that we reject. We argue and provide evidence that the tasks were (...) not too difficult for our populations and point out that in many cases performance on our tasks was well above chance or on a par with Alter et al.’s participants. Finally, we reiterate our claim that the distinction between answer fluency and perceptual fluency is genuine, and argue that Thompson et al. provided evidence that these are distinct factors that have different downstream effects on cognitive processes. (shrink)

On July 18, 1988, workers at the Metropolitan YWCA Women's Services, a Chicago-area center designed to assist women and children who are survivors of violence and sexual assault, agreed to record in a journal their thoughts at a chosen hour during that day. Each section was written by a different worker. The purpose was to bring together separate voices, all connected through their common work with survivors to begin to understand the impact of this work on their own lives.

The aims of this study were to examine the effectiveness of a range of smartphone apps for managing symptoms of anxiety and depression and to assess the utility of a single-case research design for enhancing the evidence base for this mode of treatment delivery. The study was serendipitously impacted by the COVID-19 pandemic, which allowed for effectiveness to be additionally observed in the context of significant community distress. A pilot study was initially conducted using theSuperBetter app to evaluate the proposed (...) methodology, which proved successful with the four finishing participants. In the main study, 39 participants commenced, with 29 finishing the intervention phase and completing post-intervention measures. At 6-month follow-up, a further three participants could not be contacted. This study used a digitally enhanced, multiple baseline across-individuals single-case research design. Participants were randomly assigned to the following apps:SuperBetter,Smiling Mind,MoodMission,MindShift, andDestressify. Symptomatology and life functioning were measured at five different time points: pre-baseline/screening, baseline, intervention, 3-week post-intervention, and 6-month follow-up. Detailed individual perceptions and subjective ratings of the apps were also obtained from participants following the study’s completion. Data were analyzed using visual inspection, time-series analysis, and methods of statistical and clinical significance. Positive results were observed for all apps. Overall, more favorable outcomes were achieved by younger participants, those concurrently undertaking psychotherapy and/or psychotropic medication, those with anxiety and mixed anxiety and depression rather than stand-alone depression, and those with a shorter history of mental illness. Outcomes were generally maintained at 6-month follow-up. It was concluded that a diverse range of evidence-based therapies offered via apps can be effective in managing mental health and improving life functioning even during times of significant global unrest and, like all psychotherapies, are influenced by client features. Additionally, this single-case research design is a low-cost/high value means of assessing the effectiveness of mental health apps.Clinical Trial Registration: The study is registered with the Australian and New Zealand Clinical Trials Registry, which is a primary registry in the World Health Organization Registry Network, registration number ACTRN12619001302145p. (shrink)

The principles of autonomy, beneficence, non-maleficence, and justice are well established ethical principles in health research. Of these principles, justice has received less attention by health researchers. The purpose of this article is to broaden the discussion of health research ethics, particularly the ethical principle of justice, to include societal considerations — who and what are studied and why? — and to critique current applications of ethical principles within this broader view. We will use a feminist intersectional approach in the (...) context of health disparities research to firmly establish inseparable links between health research ethics, social action, and social justice. The aim is to provide an ethical approach to health disparities research that simultaneously describes and seeks to eliminate health disparities. (shrink)

The Farmers Market Nutrition Program (FMNP) is a federal-state partnership designed to provide fresh, locally grown produce to low-income participants at nutritional risk and expand consumer awareness and use of local produce sold at farmers markets. This paper describes the results of a collaboration initiative based on the typology of a “comprehensive, multisectorial collaboration” to support the FMNP. We report the outcomes of the partnerships that developed over three years, including increased outreach to FMNP participants and strategies to decrease barriers (...) to participation. Those partnerships that reached higher degrees of coordination or collaboration are now addressing market accessibility and market quality in new ways. Those partnerships that exhibited the highest degree of collaboration are contributing to community capacity building beyond FMNP issues per se and to larger issues affecting the agriculture community and the food security of residents. (shrink)

In this article, I consider how the epistemic problem of religious disagreement has been viewed within the Islamic tradition. Specifically, I consider two religious epistemological trends within the tradition: Islamic Rationalism and Islamic Traditionalism. In examining the approaches of both trends toward addressing the epistemic problem, I suggest that neither is wholly adequate. Nonetheless, I argue that both approaches offer insights that might be relevant to building a more adequate response. So, I attempt to combine insights from both by drawing (...) a distinction between inferential and noninferential reflective responsibility. Given this distinction, I argue that it may be possible for a theist to remain steadfast in upholding their tradition-specific theistic belief, without having to hold that belief by way of inference; but nevertheless, having to be sufficiently reflectively responsible in forming their theistic belief noninferentially. (shrink)

"Databases containing the accumulated genomic data of the research community are growing exponentially. This book contains cutting-edge insights from scholars, bioethicists and legal practitioners who work at the ever-changing intersection of law and bioinformatics"--Page 4 of cover.

There was a methodological revolution in the mathematics of the nineteenth century, and philosophers have, for the most part, failed to notice.2 My objective in this chapter is to convince you of this, and further to convince you of the following points. The philosophy of mathematics has been informed by an inaccurately narrow picture of the emergence of rigour and logical foundations in the nineteenth century. This blinkered vision encourages a picture of philosophical and logical foundations as essentially disengaged from (...) ongoing mathematical practice. Frege is a telling example: we have misunderstood much of what Frege was trying to do, and missed the intended significance of much of what he wrote, because our received stories underestimate the complexity of nineteenth-century mathematics and mislocate Frege’s work within that context. Given Frege’s perceived status as a paradigmatic analytic philosopher, this mislocation translates into an unduly narrow vision of the relation between mathematics and philosophy. This chapter surveys one part of a larger project that takes Frege as a benchmark to fix some of the broader interest and philosophical significance of nineteenth-century developments. To keep this contribution to a manageable.. (shrink)

In this work, Jamie Mayerfeld undertakes a careful inquiry into the meaning and moral significance of suffering. Understanding suffering in hedonistic terms as an affliction of feeling, he claims that it is an objective psychological condition, amenable to measurement and interpersonal comparison, although its accurate assessment is never easy. Mayerfeld goes on to examine the content of the duty to prevent suffering and the weight it has relative to other moral considerations. He argues that the prevention of suffering is (...) morally more important than the promotion of happiness, and that the duty to relieve suffering is much stronger than most of us acknowledge. (shrink)

This paper compares different normative and institutional paradigms of journalism with respect to peaceful conflict resolution and democratic communication. It begins with the problematic but still dominant 'regime of objectivity,' and then considers three contemporary challengers: peace journalism, alternative media, and media democratization/communication rights movements. The paradigms are compared in terms of such factors as public philosophy, epistemological assumptions, characteristic practices, institutional entailments, relationship to dominant institutions and power structures, allies and opponents, and antagonisms and synergies between them. I conclude (...) that while peace journalism is a promising initiative, it could gain traction by exploring synergies with the other challenger paradigms. (shrink)

A cluster of recent papers on Frege have urged variations on the themethat Frege’s conception of logic is in some crucial way incompatible with‘metatheoretic’ investigation. From this observation, significant consequencesfor our interpretation of Frege’s understanding of his enterprise are taken tofollow. This chapter aims to critically examine this view, and to isolate whatI take to be the core of truth in it. However, I will also argue that once wehave isolated the defensible kernel, the sense in which Frege was committedto (...) rejecting ‘metatheory’ is too narrow and uninteresting to support the con-clusions drawn from the thesis by its proponents. (shrink)

Prompted by the development of the Theory of Challenge and Threat States in Athletes (Jones et al, 2009), recent years has witnessed a considerable increase in research examining challenge and threat in sport. This manuscript provides a critical review of the literature examining challenge and threat in sport, tracing its historical development and some of the current empirical ambiguities. In an attempt to reconcile some of these ambiguities, and utilising neurobiological evidence associated with approach- and avoidance-motivation (cf. Elliot & Covington, (...) 2001), this paper draws upon the Evaluative Space Model (ESM: Cacioppo et al., 1997) and considers the implications for understanding challenge and threat in sport. For example, rather than see challenge and threat as opposite ends of a single bipolar continuum, the ESM implies that individuals could be (1) challenged, (2) threatened, (3) challenged and threatened, or (4) neither challenged or threatened by a particular stimulus. From this perspective it could be argued that the appraisal of some sport situations as both challenging and threatening could be advantageous, whereas the current literature seems to imply that the appraisal of stress as a threat is maladaptive for performance. In drawing upon the ESM, we outline the Evaluative Space Approach to Challenge and Threat and provide several testable hypotheses for advancing understanding of challenge and threat (in sport). We also outline a number of cardiovascular and experiential measures that can be used to examine these hypotheses. In sum, this paper provides a significant theoretical, empirical and practical contribution to our understanding of challenge and threat (in sport). (shrink)

Drawing on the latest European Research on Meister Eckhart since 1970, the volume provides a comprehensive rereading of the Life, Works, Career, Trial of Meister Eckhart.

In reference to the philosophical theology of medieval Islamic theologian Ibn Taymiyya, this paper outlines a parallel between Taymiyyan thought and Alvin Plantinga’s thesis of ‘Reformed Epistemology’. In critiquing a previous attempt to build an account of ‘Islamic externalism’, the Taymiyyan model offers an account that can be seen as wholly ‘Plantingan’.

Our team at the Centre for Clinical Ethics has long been engaged in internal discussion about the purpose and value of ethics debriefs and their purported role in reducing moral distress (Morley an...

We tested the hypothesis that choices determined by Type 1 processes are compelling because they are fluent, and for this reason they are less subject to analytic thinking than other answers. A total of 104 participants completed a modified version of Wason's selection task wherein they made decisions about one card at a time using a two-response paradigm. In this paradigm participants gave a fast, intuitive response, rated their feeling of rightness for that response, and were then allowed free time (...) to reconsider their answers. As we predicted, answers consistent with a matching heuristic were made more quickly than other answers, were given higher FOR ratings, and received less subsequent analysis as measured by rethinking time and the probability of changing answers. These data suggest that reasoning biases may be compelling because they are fluently generated; this is turn creates a strong FOR, which acts as a signal that further analysis is not necessary. (shrink)

Amongst intellectuals and activists, neoliberalism has become a potent signifier for the kind of free-market thinking that has dominated politics for the past three decades. Forever associated with the conviction politics of Ronald Reagan and Margaret Thatcher, the free-market project has since become synonymous with the 'Washington consensus' on international development policy and the phenomenon of corporate globalization, where it has come to mean privatization, deregulation, and the opening up of new markets. But beyond its utility as a protest slogan (...) or buzzword as shorthand for the political-economic Zeitgeist, what do we know about where neoliberalism came from and how it spread? Who are the neoliberals, and why do they studiously avoid the label? Constructions of Neoliberal Reason presents a radical critique of the free-market project, from its origins in the first half of the 20th Century through to the recent global economic crisis, from the utopian dreams of Friedrich von Hayek through the dogmatic theories of the Chicago School to the hope and hubris of Obamanomics. The book traces how neoliberalism went from crank science to common sense in the period between the Great Depression and the age of Obama. Constructions of Neoliberal Reason dramatizes the rise of neoliberalism and its uneven spread as an intellectual, political, and cultural project, combining genealogical analysis with situated case studies of formative moments throughout the world, like New York City's bankruptcy, Hurricane Katrina, and the Wall Street crisis of 2008. The book names and tracks some of neoliberalism's key protagonists, as well as some of the less visible bit-part players. It explores how this adaptive regime of market rule was produced and reproduced, its logics and limits, its faults and its fate. (shrink)

This investigation is motivated by the lack of scholarship examining the content of what firms are communicating to various stakeholders about their commitment to socially responsible behaviors. To address this query, a qualitative study of the legal, ethical and moral statements available on the websites of Forbes Magazine''s top 50 U.S. and top 50 multinational firms of non-U.S. origin were analyzed within the context of stakeholder theory. The results are presented thematically, and the close provides implications for social responsibility among (...) managers of global organizations as well as researchers interested in business ethics. (shrink)

Despite the prominence of person‐centred care (PCC) in nursing, there is no general agreement on the assumptions and the meaning of PCC. We sympathize with the work of others who rethink PCC towards relational, embedded, and temporal selfhood rather than individual personhood. Our perspective addresses criticism of humanist assumptions in PCC using critical posthumanism as a diffraction from dominant values We highlight the problematic realities that might be produced in healthcare, leading to some people being more likely to be disenfranchised (...) from healthcare than others. We point to the colonial, homo‐ and transphobic, racist, ableist, and ageist consequences of humanist traditions that have influenced the development of PCC. We describe the deep rooted conditions that structurally uphold inequality and undermine nursing practice that PCC reproduces. We advocate for the self‐determination of patients and emphasize that we support the fundamental mechanisms of PCC enabling patients' choice; however, without critical introspection, these are limited to a portion of humans. Last, we present limitations of our perspective based on our white*‐cisheteropatriarchy** positionality. We point to the fact that any reimagining of models such as PCC should be carefully done by listening, following, and ceding power to people with diversity dimensions*** and the lived experience or expertise that exists from diverse perspectives. We point towards Black, queer feminism, and critical disabilities studies to contextualize our point of critique with humanism and PCC to amplify equity for all people and communities. Theory and philosophy are useful to understand restrictive factors in healthcare delivery and to inform systematic strategies to improve the quality of care so as not to perpetuate the oppression of groups of people with diversity dimensions. *We purposely capitalize Black and use lower case for white to decentre whiteness and as an intentional act of antiracism (see White Homework a podcast series by Tori W. Douglas). **Cisheteropatriarchy describes people with intersecting identities of dominant social groups; cisgender is the gender identity that aligns with the gender you were assigned at birth, hetero means heterosexual, and patriarchy refers to structural systems of power based on maleness where women are often excluded and hold less power. ***With diversity dimensions, we refer to subjective lived experience and material realities of people that exist outside the ‘dominant minorities' of white‐cisheteropatriarchy, meaning groups of people in society who historically and currently hold more power and through this, structurally dominate the norms and possibilities of living for other people. (shrink)

This paper offers a defence of the distinction between agent-neutral and agent-relative reasons for action from scepticism aired by Toni Rønnow-Rasmussen. In response it is argued that the Nagelian notion of an agent-neutral reason is not incomprehensible, and that agent-neutral reasons can indeed be understood as obtaining states of affairs that count in favour of anyone and everyone performing the action they favour. Furthermore, I argue that a distinction drawn between agent-neutral and agent-relative reason-statements that express the salient features of (...) reason-constitutive states of affairs is neither reductive in the sense of reducing normative reasons to the propositional content of an agent’s mental state, nor trivial in the sense of locating the distinction merely in an agent’s description of the world. (shrink)

Ethicists, policy-makers, and the general public have questioned whether artificial entities such as robots warrant rights or other forms of moral consideration. There is little synthesis of the research on this topic so far. We identify 294 relevant research or discussion items in our literature review of this topic. There is widespread agreement among scholars that some artificial entities could warrant moral consideration in the future, if not also the present. The reasoning varies, such as concern for the effects on (...) artificial entities and concern for the effects on human society. Beyond the conventional consequentialist, deontological, and virtue ethicist ethical frameworks, some scholars encourage “information ethics” and “social-relational” approaches, though there are opportunities for more in-depth ethical research on the nuances of moral consideration of artificial entities. There is limited relevant empirical data collection, primarily in a few psychological studies on current moral and social attitudes of humans towards robots and other artificial entities. This suggests an important gap for psychological, sociological, economic, and organizational research on how artificial entities will be integrated into society and the factors that will determine how the interests of artificial entities are considered. (shrink)