Regulated secretory proteins are stored within specialized vesicles known as secretory granules. It is not known how proteins are sorted into these organelles. Regulated proteins may possess targeting signals which interact with specific sorting receptors in the lumen of the trans‐Golgi network (TGN) prior to their aggregation to form the characteristic dense‐core of the granule. Alternatively, sorting may occur as the result of specific aggregation of regulated proteins in the TGN. Aggregates may be directed to secretory granules by interaction of (...) a targeting signal on the surface with a sorting receptor. Novel targeting signals which confer on regulated proteins a tendency to aggregate under certain conditions, and in so doing cause them to be incorporated into secretory granules, have been implicated. Specific targeting signals may also play a role in directing membrane proteins to secretory granules. (shrink)

This text offers a concise explanation of how philosophical concepts underpin much medical activity, and how being aware of this can improve everyday practice. It is not a basic introduction to philosophy, but restricts itself to those aspects that have a direct impact on medical professionals.

The years from 1918 to 1945 remain central to European History. It was a breath-taking time during which the very best and very worst attributes of Mankind were on display. In the euphoria of peace which followed the end of the First World War, the Baltic States emerged as independent forces on the world stage, participating in thrilling experiments in national and transnational governance. Later, following economic collapse and in the face of rising totalitarianism among even Europe’s most cultured nations, (...) Baltic communities succumbed to nationalism too. During wartime, Baltic peoples became both victims and, sometimes, victimisers. Ultimately their victimhood lasted until the end of the Cold War, yielding consequences still discernible at the start of the twenty first century. Taking the period 1918 to 1945 as pivotal, this collection of essays examines some of the key themes in Baltic History as they are emerging today. These include appreciations of identity, autonomy and the rights of national minorities; the everyday and social foundations of international security; and the importance of historical memory to popular and political identities. (shrink)

The concept of “ethical research” holds considerable sway over the ways in which contemporary biomedical, natural, and social science investigations are funded, regulated, and practiced within a variety of countries. Some commentators have viewed this “new” means of governance positively; others, however, have been resoundingly critical, regarding it as restrictive and ethics bodies and regulations unfit for the task they have been set. Regardless, it is clear that science today is an “ethical” business. The ways in which formal and informal (...) ethical discourses and practices—what might be called “regimes of normativity”—structure scientific work and the meanings it is ascribed with have, however, been underexplored. This article attends to how science and ethics articulate; how they are, in many ways, co-produced. Exploring these processes of co-production casts into sharp relief the essential emotionality of science; the relationships investigators have with their colleagues, work, and research participants pulse with emotion, potentially shaping in important ways the very kinds of knowledge that laboratories produce. (shrink)

The purpose of medical humanities is to improve the delivery of effective health care through a better understanding of disease in society, and in the individual. The interfaces between the science of medicine and the arts, philosophy, sociology and law interpret causes and effects of disease. The field of medical ethics is the most prominent offspring of this wider debate, yet the context of disease in the life of the individual and of society is profound and far-reaching. The influences of (...) medicine on the humanities and vice versa are all around, yet only recently have they been recognised in the wider world of health care. How can you encapsulate the essence of medical humanities and teach it to health professionals? Medical Humanities is designed to fill the need for a clear, well illustrated text that both provides the principles for the individual reader, and encourages discussion. The issues are explored in four main sections. Based on a highly successful seminar, and with contributions from leading writers, thinkers, and teachers, this book provides a comprehensive and authoritative reference for what is becoming a professional requirement in medicine. It will be invaluable for clinicians and students alike. (shrink)

Recent theoretical and philosophical movements within the study of material culture are more carefully attending to the variety of ways in which human artefacts, institutions, and cultural developments extend, shape and alter human cognition over time. Material Engagement Theory in particular has set out to map, explore and understand the relational nature of mind and material world as can be read through cultural artefacts. Within the context of MET, the neurological concept of metaplasticity has been expanded to include the affective (...) domains of technology, materials, and things in the neurological development and architecture of the plastic human mind; a ‘transactional’ relationship between a plastic mind and a plastic material world that are correlated at the ontological level. The challenges of mapping this metaplasticity of mind lie in understanding how the mind and material culture should be understood in relation to the constantly changing lifeworlds of humans over time; the ecological, social, technological and environmental contexts that form the historical specificity of cognitive development. This paper explores how the historical specificity of metaplasticity can be made tangible through the study of material culture, focusing upon the particular activity of oil painting. It will be argued that paintings can provide clues to the historical specificity of the mind that crosses the lifeworld of human action; the technological, phenomenological, philosophical, material, and social conditions underpinning the creation of a painted mark. Drawing from a range of sources that have a root within a Deleuzian process philosophy, the paper builds an account of painting that can be read as expressing the encultured and historical manipulation of paint as an expressive material in itself; an action rendered visible that express the historical emergence of mind. (shrink)

ArgumentResearch into the biological markers of pathology has long been a feature of British psychiatry. Such somatic indicators and associated features of mental disorder often intertwine with discourse on psychological and behavioral correlates and causes of mental ill-health. Disorders of sociality – particularly psychopathy and antisocial personality disorder – are important instances where the search for markers of pathology has a long history; research in this area has played an important role in shaping how mental health professionals understand the conditions. (...) Here, I characterize the multiplicity of psychiatric praxis that has sought to define the mark of antisociality as a form of “ontological anarchy.” I regard this as an essential feature of the search for biological and other markers of an unstable referent, positing that uncertainties endure – in part – precisely because of attempts to build consensus regarding the ontology of antisociality through biomedical means. Such an account is suggestive of the co-production of biomarkers, mental disorder, and psychiatric institutions. (shrink)

The paper examines the very different insights of theorists into the interpretation of historical meaning of literary reception and Anglo-American theorists of the "new" history of political thought . Among the former, readers create meaning; among the latter, authorial intended meanings are fundamental. Both perspectives are valuable, but one-sided. The differences between them arise from different perspectives on the character of a text. But those perspectives are not as incompatible as has been supposed, especially by reception theorists. By examining the (...) incoherences of literary reception theory when viewed from the perspective of the intentionalists, and by examining the one-sidedness of intentionalist theory in the light of a modified version of the reception perspective, it is shown that an understanding of historical meaning requires both insights. The argument is illustrated by reference to the history of political thought, a history which might more usefully be conceived as the history of political literature. (shrink)

The development of the fifth edition of the American Psychiatric Association9s _Diagnostic and Statistical Manual of Mental Disorders_—the DSM-5—has reenergised and driven further forward critical discourse about the place and role of diagnosis in mental health. The DSM-5 has attracted considerable criticism, not least about its role in processes of medicalisation. This paper suggests the need for a sociology of psychiatric critique. Sociological analysis can help map fields of contention, and cast fresh light on the assumptions and nuances of debate (...) around the DSM-5; it underscores the importance of diagnosis to the governance of social and clinical life, as well as the wider discourses critical commentaries connect with and are activated by. More normatively, a sociology of critique can indicate which interests and values are structuring the dialogues being articulated, and just how diverse clinical opinion regarding the DSM can actually be. This has implications for the considerations of health services and policy decision-makers who might look to such debates for guidance. (shrink)

Theories of affective influences on cognition posit that negative mood may increase cognitive load, causing a decrement in task performance (Seibert & Ellis, [1991]. Irrelevant thoughts, emotional mood states, and cognitive task performance. Memory & Cognition, 19(5), 507–513), or cause a shift to more analytic thinking, which benefits tasks requiring attention to detail (Schwarz & Clore, [1983]. Mood, misattribution, and judgments of well-being: Informative and directive functions of affective states. Journal of Personality and Social Psychology, 45(3), 513–523). We previously reported (...) that individuals who are higher in the trait of emotional reactivity performed better on an inhibitory task with increasing negative mood whereas low-reactive individuals showed the converse pattern (Gabel & McAuley, [2018]. Does mood help or hinder executive functions? Reactivity may be the key. Personality and Individual Differences, 128, 94–99; [2020]. React to act: Negative mood, response inhibition, and the moderating role of emotional reactivity. Motivation and Emotion, 44(6), 862–869). Because high-reactive individuals are more accustomed to negative affect (Nock et al., [2008]. The emotion reactivity scale: Development, evaluation, and relation to self-injurious thoughts and behaviors. Behavior Therapy, 39(2), 107–116), we speculated that negative mood engendered analytic thinking but without a task-incongruent increase in cognitive load – thereby facilitating performance. Here, we induced a heuristic or analytic approach to information processing prior to performance of an inhibitory task and expected different results pending the thinking style induced. In the heuristic condition, increasing negative mood was associated with better performance for high-reactive participants but not their low-reactive counterparts. In the analytic condition, increasing negative mood was associated with better performance irrespective of emotional reactivity. Our results are consistent with the notion that negative mood engenders analytic thinking which may benefit response inhibition provided it does not increase task-incongruent cognitive load. (shrink)

This book questions the generally accepted view that mechanics’ institutes made little contribution to adult working-class education from their foundation in the 1820s to 1890. The book traces the historical development of several mechanics’ institutes across Britain, establishing that many supported both male and female working-class membership before state intervention at the end of the nineteenth century resulted in the development of further education for all. Chapters of the book draw on historical accounts in supporting the claim that the movement, (...) until now seen as of little national significance, was a success, and particularly for the working classes for whom they were established. (shrink)

In the United States, the National Institute of Mental Health is seeking to encourage researchers to move away from diagnostic tools like the Diagnostic and Statistical Manual of Mental Disorders. A key mechanism for this is the “Research Domain Criteria” initiative, closely associated with former NIMH Director Thomas Insel. This article examines how key figures in US psychiatry construct the purpose, nature, and implications of the ambiguous RDoC project; that is, how its novelty is constituted through discourse. In this paper, (...) I explore and analyze these actors’ accounts of what is new, important, or desirable about RDoC, demonstrating how they are constituted through institutional context and personal affects. In my interviews with mental health opinion leaders, RDoC is presented as overly reliant on neurobiological epistemologies, distant from clinical imaginaries and imperatives, and introduced in a top-down manner inconsistent with the professional norms of scientific research. Ultimately, the article aims to add empirical depth to current understandings about the epistemological and ontological politics of contemporary psychiatry and to contribute to science and technology studies debates about “the new” in technoscience. Accordingly, I use discussions about RDoC as a case study in the sociology of novelty. (shrink)

In this book the author argues that human musical understanding is rooted in the traditions of culture and that experience of music depends crucially on what the individual brings to it.

Originally published in 1987. This book analyses what Englishmen understood by the term contract in political discussions during the late seventeenth and early eighteenth centuries. It provides evidence for reconsidering conventional accounts of the relationships between political ideas, groups and practices of the period. But also suggests cause for examining the general history of modern European contract theory. It considers contract as a term appearing in a spectrum of works from philosophical treatise to sermons and polemical pamphlets. Looking at the (...) various vocabularies relating to contractualist ideas, the author suggests that standard histories of social contract theory and particular histories of English political thought during this unstable period have misrepresented the meaning of the term contract as a key term in political argument. He shows that there were in fact three different categories of contract theory but allows that the various kinds of contractualism did share certain broad features. This study of a crucial age in the history of appeals to contract in political argument will be of interest to political philosophers and historians. features. This study of a crucial age in the history of appeals to contract in political argument will be of interest to political philosophers and historians. (shrink)

Medicine, as Byron Good argues, reconstitutes thehuman body of our daily experience as a medical body,unfamiliar outside medicine. This reconstitution can be seen intwo ways: as a salutary reminder of the extent to which thereality even of the human body is constructed; and as anarena for what Stephen Toulmin distinguishes as theintersection of natural science and history, in which many ofphilosophy''s traditional questionsare given concrete and urgent form.This paper begins by examining a number of dualities between themedical body and the (...) body familiar in daily experience. Toulmin''s epistemological analysis of clinical medicine ascombining both universal and existential knowledge is thenconsidered. Their expression, in terms of attention,respectively, to natural science and to personal history, isexplored through the epistemological contrasts between themedical body and the familiar body, noting the traditionalphilosophical questions which they in turn illustrate. (shrink)

Many bioethics questions are resistant to journalistic exploration on account of their inherently philosophical dimensions. Such dimensions are ill-suited to what we may term the internal goods (in MacIntyre's sense) of the newspapers and mass media generally, which constrain newspaper coverage to an abbreviated form of narrative that, whilst not in itself objectionable, is nonetheless inimical to the conduct of philosophical reflection. The internal goods of academic bioethics, by contrast, include attention to philosophical questions inherent in bioethical issues and value-enquiry. (...) The danger for bioethics is that its agenda for reflective enquiry will, if dictated by this abbreviated narrative, be distorted in terms of both range and priorities, to the inevitable neglect of questions having a philosophical dimension to them. This danger can be avoided by a constructive partnership between the media and academic bioethics. The success of this partnership relies on four suggested provisos, for the meeting of which both journalists and academics bear responsibility. (shrink)