The hemidesmosome is a complex junction containing many proteins. The keratin cytoskeleton attaches to its cytoplasmic plaque, while its transmembrane elements interact with components of the extracellular matrix. Hemidesmosome assembly involves recruitment of α6β4 integrin heterodimers, as well as cytoskeletal elements and cytoskeleton-associated proteins to the cell surface. In our cell culture models, these phenomena appear to be triggered by laminin-5 in the extracellular matrix. Cell interaction with laminin-5 apparently induces both phosphorylation and dephosphorylation of subunits of α6β4 integrin. There (...) is emerging evidence that such events are necessary for subsequent cytoskeleton anchorage to the hemidesmosome cytoplasmic plaque. Once assembled, the hemidesmosome plays an essential role in maintaining firm epithelial adhesion to the basement membrane, with hemidesmosome disruption being a hallmark of certain devastating blistering diseases. However, the hemidesmosome is more than just a stable anchor, as it may also be the site of signal transduction, mediated by its α6β4 integrin component. This review discusses our current knowledge of the structure and assembly of the hemidesmosome. BioEssays 20:488–494, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

This paper describes a pilot study of a new model for narrative medicine training, “community-based participatory narrative medicine”, which centers on shared narrative work between healthcare trainees and patients. Nine medical students and eight patients participated in one of two, five-week-long pilot workshop series. A case study of participants’ experiences of the workshop series identified three major themes: the reciprocal and collaborative nature of participants’ relationships; the interplay between self-reflection and receiving feedback from others; and the clinical and pedagogical implications (...) of the CBPNM model. Principles and proposed outcomes of the CBPNM model are presented. (shrink)

Pioneering work in the 1940s and 1950s suggested that the concept of chunking might be important in many processes of perception, learning and cognition in humans and animals. We summarize here the major sources of evidence for chunking mechanisms, and consider how such mechanisms have been implemented in computational models of the learning process. We distinguish two forms of chunking: the first deliberate, under strategic control, and goal-oriented; the second automatic, continuous, and linked to perceptual processes. Recent work with discrimination-network (...) computational models of long- and short-term memory (EPAM/CHREST) has produced a diverse range of applications of perceptual chunking. We focus on recent successes in verbal learning, expert memory, language acquisition and learning multiple representations, to illustrate the implementation and use of chunking mechanisms within contemporary models of human learning. (shrink)

Deception sometimes results in nonconsensual sex. A recent body of literature diagnoses such violations as invalidating consent: the agreement is not morally transformative, which is why the sexual contact is a rights violation. We pursue a different explanation for the wrongs in question: there is valid consent, but it is not consent to the sex act that happened. Semantic conventions play a key role in distinguishing deceptions that result in nonconsensual sex (like stealth condom removal) from those that don’t (like (...) white lies). Our framework is also applicable to more controversial cases, like those implicated in so-called “gender fraud” complaints. (shrink)

Almost uniquely for someone whose thought has been so influential, Socrates wrote nothing himself, and our knowledge of his philosophical opinions and method is derived mainly from the engaging and infuriating figure who appears in Plato's dialogues. The philosophy of Socrates and Plato is therefore closely interconnected, and the most powerful elements of Plato's mature thought form the basis of an interpretation of knowledge, reality, and morality which is still held and debated by philosophers today. Aristotle's approach to these and (...) other issues is in many ways directly opposed to that of Plato, and has been no less influential. (shrink)

The internet is widely used for health information and support, often by vulnerable people. Internet-based research raises both familiar and new ethical problems for researchers and ethics committees. While guidelines for internet-based research are available, it is unclear to what extent ethics committees use these. Experience of gaining research ethics approval for a UK study (SharpTalk), involving internet-based discussion groups with young people who self-harm and health professionals is described. During ethical review, unsurprisingly, concerns were raised about the vulnerability of (...) potential participants. These were dominated by the issue of anonymity, which also affected participant safety and consent. These ethical problems are discussed, and our solutions, which included: participant usernames specific to the study, a closed website, private messaging facilities, a direct contact email to researchers, information about forum rules displayed on the website, a ‘report’ button for participants, links to online support, and a discussion room for forum moderators. This experience with SharpTalk suggests that an approach to ethics, which recognises the relational aspects of research with vulnerable people, is particularly useful for internet-based health research. The solutions presented here can act as guidance for researchers developing proposals and for ethics committees reviewing them. (shrink)

Recognising and responding appropriately to emotions is critical to adaptive psychological functioning. Psychopathic traits (e.g. callous, manipulative, impulsive, antisocial) are related to differences in recognition and response when emotion is conveyed through facial expressions and language. Use of emotional music stimuli represents a promising approach to improve our understanding of the specific emotion processing difficulties underlying psychopathic traits because it decouples recognition of emotion from cues directly conveyed by other people (e.g. facial signals). In Experiment 1, participants listened to clips (...) of emotional music and identified the emotional content (Sample 1, N = 196) or reported on their feelings elicited by the music (Sample 2, N = 197). Participants accurately recognised (t(195) = 32.78, p <.001, d = 4.69) and reported feelings consistent with (t(196) = 7.84, p <.001, d = 1.12) the emotion conveyed in the music. However, psychopathic traits were associated with reduced emotion recognition accuracy (F(1, 191) = 19.39, p <.001) and reduced likelihood of feeling the emotion (F(1, 193) = 35.45, p <.001), particularly for fearful music. In Experiment 2, we replicated findings for broad difficulties with emotion recognition (Sample 3, N = 179) and emotional resonance (Sample 4, N = 199) associated with psychopathic traits. Results offer new insight into emotion recognition and response difficulties that are associated with psychopathic traits. (shrink)

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR and SPINK1 variants were associated with pancreatitis risk. We now report two associations at genome-wide significance identified and replicated at PRSS1-PRSS2 and X-linked CLDN2 through a two-stage genome-wide study. The PRSS1 variant likely affects disease susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is (...) associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men. © 2012 Nature America, Inc. All rights reserved. (shrink)

Jeffery Aubin ,Marie Chantal ,Dianne Cole ,Julio Chaves ,Cathelyne Duchesne ,Christel Freu ,Steve Johnston ,Brice Jones ,Amaury Levillayer ,Stéphanie Machabée ,Paul-Hubert Poirier ,Philippe Therrien ,Jonathan von Kodar ,Martin Voyer ,Jennifer Wees ,Eric Crégheur.

The paper is written in response to those who fail to recognize the relation between a patient's mental competency and her state of pain. Some clinicians claim that a proper diagnosis can only be made in the absent of analgesia. Rather, the patient's state of pain directly affects her mental competency and thus her ability to give valid consent. Clinicians should rethink their approach to diagnosis when the patient is in pain.

“Tell me," Wittgenstein once asked a friend, "why do people always say, it was natural for man to assume that the sun went round the earth rather than that the earth was rotating?" His friend replied, "Well, obviously because it just looks as though the Sun is going round the Earth." Wittgenstein replied, "Well, what would it have looked like if it had looked as though the Earth was rotating?” What would it have looked like if we looked at all (...) sciences from the viewpoint of Wittgenstein’s philosophy? Wittgenstein is undoubtedly one of the most influential philosophers of the twentieth century. His complex body of work has been analysed by numerous scholars, from mathematicians and physicists, to philosophers, linguists, and beyond. This volume brings together some of his central perspectives as applied to the modern sciences and studies the influence they may have on the thought processes underlying science and on the world view it engenders. The contributions stem from leading scholars in philosophy, mathematics, physics, economics, psychology and human sciences; all of them have written in an accessible style that demands little specialist knowledge, whilst clearly portraying and discussing the deep issues at hand. (shrink)

Some of the authors of the essays on Chinese philosophers prefer the pin yin system of romanization for Chinese names and words, while others prefer the Wade‐Giles system. Given that both systems are in wide use today, important names and words are given in both their pin yin and Wade‐Giles formulations. The author's preference is printed first, followed by the alternative romanization within brackets.

It is argued that "a's statement, That x is eligible, Is true" says, And not merely presupposes as williams holds, That x is eligible. A brief summary is given of williams' analysis of what is said about a statement when it is said to be true. An attempt is made to show that the predicable in williams' definition is anomalous by contrasting it with genuine conjunctive predicables. Finally, It is suggested that williams' predicable, Even if suitably modified, Would not be (...) the formal equivalent of "things are as a says they are", Which is what williams had claimed. (shrink)

The 17th century witnessed a remarkable religious revival in France which rapidly assumed a very definite mystical trend. Historians are quick to point out that it was in fact a continuation of the mystical flowering which characterised the Spanish church in the previous hundred years. Side by side with the large number of ‘mystics’, both clerical and lay, male and female, went the powerful group of the ‘anti-mystics’—mainly clerical—who distrusted all that ‘Dionysian balderdash’, to quote the words of Father Binet (...) in 1624. Even the great Teresa of Avila fell into disrepute and the Carmelites were more often than not embarrassed by the mystical experiences recounted in the life of John of the Cross. (shrink)

The Search for the Legacy of the USPHS Syphilis Study at Tuskegee is a collection of essays from experts in a variety of fields seeking to redefine the legacy of the infamous Tuskegee Syphilis Study. The essayists place the legacy of the study within the evolution of racial and ethnic relations in the United States. Contributors include two leading historians on the study, two former United States Surgeons General, and other prominent scholars from a wide range of fields.

Early versions of satellite and radiosonde datasets suggested that the tropical surface had warmed more than the troposphere, while climate models consistently showed tropospheric amplification of surface warming in response to human-caused increases in greenhouse gases. We revisit such comparisons here using new observational estimates of surface and tropospheric temperature changes. We find that there is no longer a serious discrepancy between modeled and observed trends in the tropics. Our results contradict a recent claim that all simulated temperature trends in (...) the tropical troposphere are inconsistent with observations. This claim was based on the use of older radiosonde and satellite datasets and on two methodological errors: the neglect of observational trend uncertainties introduced by interannual climate variability and application of an inappropriate statistical “consistency test”.This emerging reconciliation of models and observations has two primary explanations. First, because of changes in the treatment of buoy and satellite information, new surface temperature datasets yield slightly reduced tropical warming relative to earlier versions. Second, recently developed satellite and radiosonde datasets now show larger warming of the tropical lower troposphere. In the case of a new satellite dataset from remote sensing systems, enhancedRSS warming is due to an improved procedure of adjusting for inter-satellite biases. When the RSS-derived tropospheric temperature trend is compared with four different observed estimates of surface temperature change, the surface warming is invariably amplified in the tropical troposphere, consistent with model results. Even if we use data from a second satellite dataset with smaller tropospheric warming than in remote sensing systems RSS, observed tropical lapse rates are not significantly different from those in all model simulations.Our results contradict a recent claim that all simulated temperature trends in the tropical troposphere and in tropical lapse rates are inconsistent with observations. This claim was based on the use of older radiosonde and satellite datasets and on two methodological errors: the neglect of observational trend uncertainties introduced by interannual climate variability and application of an inappropriate statistical “consistency test”. (shrink)

Public health ethics, like the field of public health it addresses, traditionally has focused more on practice and particular cases than on theory, with the result that some concepts, methods, and boundaries remain largely undefined. This paper attempts to provide a rough conceptual map of the terrain of public health ethics. We begin by briefly defining public health and identifying general features of the field that are particularly relevant for a discussion of public health ethics.Public health is primarily concerned with (...) the health of the entire population, rather than the health of individuals. Its features include an emphasis on the promotion of health and the prevention of disease and disability; the collection and use of epidemiological data, population surveillance, and other forms of empirical quantitative assessment; a recognition of the multidimensional nature of the determinants of health; and a focus on the complex interactions of many factors—biological, behavioral, social, and environmental—in developing effective interventions. (shrink)

Spillover occurs when one environmentally sustainable behaviour leads to another, often initiated by a behaviour change intervention. A number of studies have investigated positive and negative spillover effects, but empirical evidence is mixed, showing evidence for both positive and negative spillover effects, and lack of spillover altogether. Environmental identity has been identified as an influential factor for spillover effects. Building on identity process theory the current framework proposes that positive, negative, and a lack of spillover are determined by perceived threat (...) of initial behaviour and identity process mechanisms evaluating the behaviour. It is proposed, that an environmental behaviour change intervention may threaten one’s existing identities, leading to either (a) integration, (b) compartmentalisation, or (c) conflict between one’s environmental identity and non-environmental identities. Initial evidence for the proposed framework is based on a field intervention which included a meat reduction programme in a canteen of a medium size private sector company. Semi-structured interviews and an explorative visualisation method that aimed at assessing identity change were implemented with thirteen employees (i.e. intervention participants) before and after the intervention. The qualitative data was analysed by using thematic analysis via NVivo12. Results of the visualisation task and interview method provided initial evidence of direct and indirect positive contextual spillover effects, with comparatively less evidence a lack of spillover and a relative absence of reported negative spillover. This paper provides a novel theoretical approach, centred on identity process theory to enhance understanding of positive spillover, negative spillover, and the lack of spillover. (shrink)