Positive transcription elongation factor b (P‐TEFb), which comprises cyclin‐dependent kinase 9 (CDK9) kinase and cyclin T subunits, is an essential kinase complex in human cells. Phosphorylation of the negative elongation factors by P‐TEFb is required for productive elongation of transcription of protein‐coding genes by RNA polymerase II (pol II). In addition, P‐TEFb‐mediated phosphorylation of the carboxyl‐terminal domain (CTD) of the largest subunit of pol II mediates the recruitment of transcription and RNA processing factors during the transcription cycle. CDK9 also phosphorylates (...) p53, a tumor suppressor that plays a central role in cellular responses to a range of stress factors. Many viral factors affect transcription by recruiting or modulating the activity of CDK9. In this review, we will focus on how the function of CDK9 is regulated by viral gene products. The central role of CDK9 in viral life cycles suggests that drugs targeting the interaction between viral products and P‐TEFb could be effective anti‐viral agents. (shrink)

IntroductionInternational sharing of health data opens the door to the study of the so-called ‘Big Data’, which holds great promise for improving patient-centred care. Failure of recent data sharing initiatives indicates an urgent need to invest in societal trust in researchers and institutions. Key to an informed understanding of such a ‘social license’ is identifying the views patients and the public may hold with regard to data sharing for health research.MethodsWe performed a narrative review of the empirical evidence addressing patients’ (...) and public views and attitudes towards the use of health data for research purposes. The literature databases PubMed, Embase, Scopus and Google Scholar were searched in April 2019 to identify relevant publications. Patients’ and public attitudes were extracted from selected references and thematically categorised.ResultsTwenty-seven papers were included for review, including both qualitative and quantitative studies and systematic reviews. Results suggest widespread—though conditional—support among patients and the public for data sharing for health research. Despite the fact that participants recognise actual or potential benefits of data research, they expressed concerns about breaches of confidentiality and potential abuses of the data. Studies showed agreement on the following conditions: value, privacy, risk minimisation, data security, transparency, control, information, trust, responsibility and accountability.ConclusionsOur results indicate that a social license for data-intensive health research cannot simply be presumed. To strengthen the social license, identified conditions ought to be operationalised in a governance framework that incorporates the diverse patient and public values, needs and interests. (shrink)

Is there a limit to the legitimate demands of morality? In particular, is there a limit to people's responsibility to promote the well-being of others, either directly or via social institutions? Utilitarianism admits no such limit, and is for that reason often said to be an unacceptably demanding moral and political view. In this original new study, Murphy argues that the charge of excessive demands amounts to little more than an affirmation of the status quo. The real problem with (...) utilitarianism is that it makes unfair demands on people who comply with it in our world of nonideal compliance. Murphy shows that this unfairness does not arise on a collective understanding of our responsibility for others' well being. Thus, according to Murphy, while there is no general problem to be raised about the extent of moral demands, there is a pressing need to acknowledge the collective nature of the demands of beneficence. (shrink)

Pragmatic trials aim to directly inform health care decision-making through the collection of so-called ‘real world data’ from observations of comparative treatment effects in clinical practice. In order to ensure the applicability and feasibility of a pragmatic trial, design features may be necessary that deviate from standard research ethics requirements. Examples are traditional requirements to seek written informed consent and to perform extensive data and safety monitoring. Proposals for deviations from standard research ethics practice have resulted in controversy about their (...) ethical acceptability. One of the justifications for altered procedures is the allegedly high social value of pragmatic trials. In order to properly operationalize the concept in the ethical assessment of pragmatic trial designs, specification is warranted. We identified three determinants from common claims about a pragmatic trial's social value: the extent to which the research question has real world relevance, the trial design's ability to generate a real world answer and the probability of direct uptake of the results by decision-makers in practice. Subsequently, we discuss how these determinants should be applied to the practice of pragmatic trials, and to what extent they might be applicable to explanatory trials. (shrink)

Large-scale linkage of international clinical datasets could lead to unique insights into disease aetiology and facilitate treatment evaluation and drug development. Hereto, multi-stakeholder consortia are currently designing several disease-specific translational research platforms to enable international health data sharing. Despite the recent adoption of the EU General Data Protection Regulation, the procedures for how to govern responsible data sharing in such projects are not at all spelled out yet. In search of a first, basic outline of an ethical governance framework, we (...) set out to explore relevant ethical principles and norms. We performed a systematic review of literature and ethical guidelines for principles and norms pertaining to data sharing for international health research. We observed an abundance of principles and norms with considerable convergence at the aggregate level of four overarching themes: societal benefits and value; distribution of risks, benefits and burdens; respect for individuals and groups; and public trust and engagement. However, at the level of principles and norms we identified substantial variation in the phrasing and level of detail, the number and content of norms considered necessary to protect a principle, and the contextual approaches in which principles and norms are used. While providing some helpful leads for further work on a coherent governance framework for data sharing, the current collection of principles and norms prompts important questions about how to streamline terminology regarding de-identification and how to harmonise the identified principles and norms into a coherent governance framework that promotes data sharing while securing public trust. (shrink)

The ideal introduction for students of semantics, Lexical Meaning fills the gap left by more general semantics textbooks, providing the teacher and the student with insights into word meaning beyond the traditional overviews of lexical relations. The book explores the relationship between word meanings and syntax and semantics more generally. It provides a balanced overview of the main theoretical approaches, along with a lucid explanation of their relative strengths and weaknesses. After covering the main topics in lexical meaning, such as (...) polysemy and sense relations, the textbook surveys the types of meanings represented by different word classes. It explains abstract concepts in clear language, using a wide range of examples, and includes linguistic puzzles in each chapter to encourage the student to practise using the concepts. 'Adopt-a-Word' exercises give students the chance to research a particular word, building a portfolio of specialist work on a single word. (shrink)

Purpose – The purpose of this study is to explore Australian public and stakeholders views towards the regulation of the Internet and its content. The federal government called for submissions addressing their proposal, and this paper analyses these submissions for themes and provides clarity as to the Australian public and stakeholders key concerns in regards to the proposed policy. Design/methodology/approach – The paper uses a qualitative approach to analyse the public consultations to the Australian Federal Government. These documents are coded (...) and analysed to determine negative and positive viewpoints. Findings – The research has shown, based upon the analysis of the consultation, that there was no public support for any of the measures put forward, that the Australian Federal Government in its response has not recognised this public feedback and instead has only utilised some of the qualitative feedback obtained through the public consultation process to try to justify its case to proceed with its proposals. Research limitations/implications – The study is focussed on Australia. Practical implications – The paper analyses a proposed national approach to filtering the content of the Internet and discussed the public reaction to such an approach. Social implications – The paper looks at how different parts of Australian society view Internet filtering in a positive or negative manner. Originality/value – The only study that directly looks at the viewpoint of the Australian public. (shrink)

This book explores how some word meanings are paradigmatically related to each other, for example, as opposites or synonyms, and how they relate to the mental organization of our vocabularies. Traditional approaches claim that such relationships are part of our lexical knowledge (our "dictionary" of mentally stored words) but Lynne Murphy argues that lexical relationships actually constitute our "metalinguistic" knowledge. The book draws on a century of previous research, including word association experiments, child language, and the use of synonyms (...) and antonyms in text. (shrink)

Can we deploy creative practices to critically address the fatal interlocking of global surveillance technologies, neo-colonial expansionism, environmental degradation and the lethal threat of drone warfare? Throughout the following conversation, Shona Illingworth and Anthony Downey examine these and other questions in relation to the recent publication of Topologies of Air (Sternberg Press and The Power Plant, 2022). Edited by Downey, the book includes discussion and documentation of two major bodies of work by Illingworth, including Topologies of Air (2021) and (...) Lesions in the Landscape (2015), alongside an extended series of essays that analyse the psychological and environmental impact of military, industrial and corporate transformations of airspace and outer space. Employing interdisciplinary research and collaborative processes, Illingworth’s practice, as detailed in the discussion below, uses creative methodologies to visualize and interrogate this proliferating exploitation of airspace. The conversation between Illingworth and Downey also outlines the work of the Airspace Tribunal, an ongoing series of public hearings that brings together diverse disciplines, methodologies, knowledge and lived experiences to propose a new human right that will counter the colonization of the sky and, in time, protect individuals, communities and ecologies from ever-increasing threats from above. (shrink)

Emotional hardcore and other music genres featuring screamed vocals are puzzling for the appreciator. The typical fan attaches appreciative value to musical screams of emotional pain all the while acknowledging it would be inappropriate to hold similar attitudes towards their sonically similar everyday counterpart: actual human screaming. Call this the screamed vocals problem. To solve the problem, I argue we must attend to the anti-sublimating aims that get expressed in the emotional hardcore vocalist’s choice to scream the lyrics. Screamed vocals (...) help us see the value in rejecting (a) restrictive social norms of emotional expressiveness and (b) restrictive artistic norms about how one ought to express or represent pain in art, namely that if one is going to do so they must ensure the pain has been ‘beautified’. In developing this second point I argue that emotional hardcore is well-suited (though not individually so) for putting pressure on longstanding views in the history of aesthetics about the formal relationship between art and human pain. (shrink)

Although many modern philosophers of law describe custom as merely a minor source of law, formal law is actually only one source of the legal customs that govern us. Many laws grow out of custom, and one measure of a law's success is by its creation of an enduring legal custom. Yet custom and customary law have long been neglected topics in unsettled jurisprudential debate. Smaller concerns, such as whether customs can be legitimized by practice or by stipulation, stipulated by (...) an authority or by general consent, or dictated by law or vice versa, lead to broader questions of law and custom as alternative or mutually exclusive modes of social regulation, and whether rational reflection in general ought to replace sub-rational prejudice. Can legal rules function without customary usage, and does custom even matter in society? The Philosophy of Customary Law brings greater theoretical clarity to the often murky topic of custom by showing that custom must be analyzed into two more logically basic concepts: convention and habit. James Bernard Murphy explores the nature and significance of custom and customary law, and how conventions relate to habits in the four classic theories of Aristotle, Francisco Suarez, Jeremy Bentham, and James C. Carter. He establishes that customs are conventional habits and habitual conventions, and allows us to better grasp the many roles that custom plays in a legal system by offering a new foundation of understanding for these concepts. (shrink)

Issues of balancing data accessibility with ethical considerations and governance of a genomics research biobank, Generation Scotland, are explored within the evolving policy landscape of the past ten years. During this time data sharing and open data access have become increasingly important topics in biomedical research. Decisions around data access are influenced by local arrangements for governance and practices such as linkage to health records, and the global through policies for biobanking and the sharing of data with large-scale biomedical research (...) data resources and consortia. We use a literature review of policy relevant documents which apply to the conduct of biobanks in two areas: support for open access and the protection of data subjects and researchers managing a bioresource. We present examples of decision making within a biobank based upon observations of the Generation Scotland Access Committee. We reflect upon how the drive towards open access raises ethical dilemmas for established biorepositories containing data and samples from human subjects. Despite much discussion in science policy literature about standardisation, the contextual aspects of biobanking are often overlooked. Using our engagement with GS we demonstrate the importance of local arrangements in the creation of a responsive ethical approach to biorepository governance. We argue that governance decisions regarding access to the biobank are intertwined with considerations about maintenance and viability at the local level. We show that in addition to the focus upon ever more universal and standardised practices, the local expertise gained in the management of such repositories must be supported. A commitment to open access in genomics research has found almost universal backing in science and health policy circles, but repositories of data and samples from human subjects may have to operate under managed access, to protect privacy, align with participant consent and ensure that the resource can be managed in a sustainable way. Data access committees need to be reflexive and flexible, to cope with changing technology and opportunities and threats from the wider data sharing environment. To understand these interactions also involves nurturing what is particular about the biobank in its local context. (shrink)

The first IVF baby was born in the 1970s. Less than 20 years later, we had cloning and GM food, and information and communication technologies had transformed everyday life. In 2000, the human genome was sequenced. More recently, there has been much discussion of the economic and social benefits of nanotechnology, and synthetic biology has also been generating controversy. This important volume is a timely contribution to increasing calls for regulation - or better regulation - of these and other new (...) technologies. Drawing on an international team of legal scholars, it reviews and develops the role of human rights in the regulation of new technologies. Three controversies at the intersection between human rights and new technology are given particular attention. First, how the expansive application of human rights could contribute to the creation of a brave new world of choice, where human dignity is fundamentally compromised; second, how new technologies, and our regulatory responses to them, could be a threat to human rights; and, third, how human rights could be used to create better regulation of these technologies. (shrink)

This article outlines an approach for implementing business ethics. A company should both organize for ethical business policies and execute them. The organizational dimension refers to structural components including codes of ethics, conferences and training programs and an ethical audit. The corporate culture must support these structural elements with top management playing a central role in implementing ethics. The execution of ethical business policies includes implementation responsibilities and tasks. These responsibilities are leadership in ethics, delegation, communication and motivation of the (...) company's ethical position to employees. Execution tasks are delineated for the marketing function. Although many company examples are provided, a program in place at McDonnell Douglas is highlighted as a model of ethics implementation. (shrink)

This book delivers a definitive contribution to the understanding of Habermas's oeuvre as it applies to education. The authors examine Habermas's contribution to pedagogy, learning and classroom interaction; the relation between education, civil society and the state; forms of democracy, reason and critical thinking; and performativity, audit cultures and accountability.

This volume identifies, discusses and addresses the wide array of ethical issues that have emerged for engineers due to the rise of a global economy. To date, there has been no systematic treatment of the particular challenges globalization poses for engineering ethics standards and education. This volume concentrates on precisely this challenge. Scholars and practitioners from diverse national and professional backgrounds discuss the ethical issues emerging from the inherent symbiotic relationship between the engineering profession and globalization. Through their discussions a (...) deeper and more complete understanding of the precise ways in which globalization impacts the formulation and justification of ethical standards in engineering as well as the curriculum and pedagogy of engineering ethics education emerges. (shrink)

A challenging critique of narrative theologies, including the works of George Lindbeck, Robert Jenson, and Herbert McCabe. Francesca Aran Murphy argues that the use of the concept of story or narrative in theology is circular and self-referential, and that the widespread notion that the role of the theologian is to 'tell God's story' has not helped theology to advance the reality of its doctrines. Murphy contends that the scriptural revelation on which Christian theology depends is not a story (...) or a plot but a dramatic encounter between mysterious, free, and unpredictable persons. She offers her own alternative approach, making use of cinema and film theory, and engaging in particular in a dialogue with the work of Hans Urs von Balthasar. (shrink)

The Collective Imagination explores the social foundations of the human imagination. A comprehensive audit of the creativity claims of the post-modern age - that finds them badly wanting and looks to the future - this book will appeal to sociologists and philosophers concerned with cultural theory, cultural and media studies and aesthetics.

When first published twenty years ago, The Logic of Medicine presented a new way of thinking about clinical medicine as a scholarly discipline as well as a profession. Since then, advances in research and technology have revolutionized both the practice and theory of medicine. In this new, extensively rewritten edition, Dr. Murphy includes changes to show how these different areas of scholarship may affect details of "the logic of medicine" without compromising its fundamental coherence. New to this edition are (...) discussions of the challenge of the flood of new empirical data, new ideas in genetics, molecular biology, homeostasis, pathogenesis, cancer, aging, and Alzheimer's disease. Murphy also comments on such new theoretical topics as dynamic systems, chaos, and fractals and their impact on the burgeoning fields of philosophy and practice of medicine. Written with medical students in mind, the book includes a glossary, many new examples, and problems for solutions with comments on each. An entirely new chapter deals with modeling. Clinicians and researchers will also find the principles thought-provoking and illuminating. (shrink)

This article draws on the free‐text commentaries from trans‐Tasman studies that used the MISSCARE questionnaire to explore the reasons why nurses miss care. In this paper, we examine the idea that nurses perpetuate a self‐effacing approach to care, at the expense of patient care and professional accountability, using what they describe as the art of nursing to frame their claims of both nursing care and missed nursing care. We use historical dialogue alongside a paradigmatic analysis to examine why nurses allow (...) themselves to continue working within settings that put their professional/personal selves aside in an attempt to deliver care within constraints that make completing care an impossible task. The findings suggest an ambivalence and conflict confront nurses attempting to provide care within the New Public Management environment. This can be seen in the tensions that draw a line between care as an art, and care as a financial target, juxtaposed with the inherent clash of values arising from the way nursing care is conceptualised within two contradictory paradigms. (shrink)

Habermas: a closet Kantian -- Kant -- Vattimo: a closet Kantian -- Gadamer and Lyotard on aesthetic judgment (I): some problems -- Gadamer and Lyotard on aesthetic judgment (II): the story of where they go wrong.

Objections to the principle of double effect usually concern its first and second conditions (that the act not be evil in itself, and that the evil effect may not be intended). The difficulties often arise from a rejection of the idea that acts have a moral nature independent of context, and a tendency to interpret intention as purely psychological. This article argues that the “act itself” should be understood as the act-type and suggests that examples of evil act-types are not (...) hard to find. It argues that the notion of intention is involved in both conditions, but in different ways. It proposes that these different ways can be interestingly illuminated by Anscombe’s distinction between acting intentionally and acting with an intention. (shrink)

The rhetoric of moral, spiritual and political decline represents a recurrent rhetorical form, one that has appeared throughout history in a variety of contexts. This article takes a closer look at one episode in the history of decline rhetoric -- the fourth-century anti-Christian critiques regarding Roman imperial decline, and Augustine's responses to them in his City of God -- in order to explore the phenomenon of decline rhetoric more deeply. Augustine's response to those who blamed Christianity for the empire's decline (...) took place on both the empirical and the interpretive levels. First, he drew on the Roman historians Sallust and Livy to argue that moral decline, if it took place at all, predated Christianity. Second, his theory of the two cities took issue with the notion of decline as a fundamental misunderstanding of historical change. The article closes by drawing out some implications of this particular study for approaching decline rhetoric in political life more generally, concluding with a consideration of the controversial remarks of Pat Robertson and Jerry Falwell, who viewed the 11 September attacks as divine punishment for American moral decline. (shrink)

This book provides a rich collection of readings that challenge traditional understandings of knowledge and the view of mind that underpins them.

_Stranger Cities_ explores the nature of Australia’s distinctive urban civilization with its portal ontology, axial metaphysics, ambidextrous style of thinking, architectonic spirit, and happy phlegmatic outlook. This classic ethos is offset by various choleric and melancholic strands of Australian romanticism.

This chapter offers a general outline of Schopenhauer’s peculiarly named concept of the 'acquired character’ and explains its basic function in his ethical thought. For Schopenhauer, a person of acquired character is someone who knows the ways of acting (Handlungsweise) that are most expressive of their individuality and who allows that self-knowledge to structure their practical and emotional life. In keeping with certain elements of his psychological determinism, acquired character is not the acquisition of a ‘new’ character; rather, it is (...) the acquisition of self-knowledge of one’s essentially fixed empirical character. It is part of the argument of this chapter that by introducing the acquired character into his reflections on human action and agency Schopenhauer weaves a certain view of individual flourishing (eudaimonia) into his ethics. There are two central ingredients of Schopenhauer’s conception of eudaimonia, and both are linked to the acquired character. The first is self-knowledge; the second is a sense of personal autonomy that follows in the wake of the first. The chapter ends with a brief attempt to connect Schopenhauer’s concept of acquired character to contemporary debates in ethics concerning autonomy, practical identity, and what some call the ‘normative significance of self’. (shrink)

This paper is about the nature of God’s pre-creation knowledge of possible creatures. I distinguish three theories: non-qualitative singularism, qualitative singularism, and qualitative generalism, which differ in terms of whether the relevant knowledge is qualitative or non-qualitative, and whether God has singular or merely general knowledge of creatures. My main aim is to argue that qualitative singularism does not depend on a version of the Principle of Identity of Indiscernibles to the effect that, necessarily, qualitatively indiscernible individuals are identical. It (...) follows that qualitative singularism does not depend on the view that possible creatures categorically have qualitative individual essences. (shrink)

Granting that there could be true subjunctive conditionals of libertarian freedom (SCLs), I argue (roughly) that there could be such conditionals only in connection with individual "possible creatures" (in contrast to types). This implies that Molinism depends on the view that, prior to creation, God grasps possible creatures in their individuality. In making my case, I explore the notions of counterfactual implication (that relationship between antecedent and consequent of an SCL which consists in its truth) and counterfactual relevance (that feature (...) of an antecedent in virtue of which it counterfactually implies something or other). (shrink)

Quentin Smith has argued that quantum-cosmological theory is incompatible with theism. The two claims that Smith argues render theism inconsistent with Hawking’s theory are that of the initial creation of the universe by God and His continued conservation of it. His primary argument is that divine decision and Hawking’s wave function entail contradictory probabilities that the universe begin to exist and continue to evolve in a certain way. I attempt to refute the argument by providing a schema that accommodates probabilities (...) conditioned on divine decision as well as those conditioned on the wave function with respect to these two issues. (shrink)

An apparently quite specific question that was addressed by both Confucius and Socrates has attracted much attention in Sino-Hellenistic comparative philosophy. Their respective responses to the question of how a son should respond if his father commits a crime are found in Confucius' Analects 13:18 and in Plato's Euthyphro. This essay assesses three comparative analyses of these responses with particular reference to their underlying assertions of commonality, that is, the assumptions or presuppositions of commonality that serve to justify the comparative (...) exercise in the first instance. The authors suggest that two of the analyses assert commonality between their two responses from a Confucian standpoint, while the third constructs commonality from a Socratic standpoint. The authors argue that the response of Confucius focuses specifically on the issue of xiao (filial piety) in the concrete situation presented to him, whereas Socrates uses the issue to investigate the different question known as the "Euthyphro dilemma." Some brief conclusions are drawn regarding comparative philosophical analysis in general and about comparing the responses of Confucius and Socrates in these passages in particular. (shrink)

An apparently quite specific question that was addressed by both Confucius and Socrates has attracted much attention in Sino-Hellenistic comparative philosophy. Their respective responses to the question of how a son should respond if his father commits a crime are found in Confucius' Analects 13:18 and in Plato's Euthyphro. This essay assesses three comparative analyses of these responses with particular reference to their underlying assertions of commonality, that is, the assumptions or presuppositions of commonality that serve to justify the comparative (...) exercise in the first instance. The authors suggest that two of the analyses assert commonality between their two responses from a Confucian standpoint, while the third constructs commonality from a Socratic standpoint. The authors argue that the response of Confucius focuses specifically on the issue of xiao in the concrete situation presented to him, whereas Socrates uses the issue to investigate the different question known as the "Euthyphro dilemma." Some brief conclusions are drawn regarding comparative philosophical analysis in general and about comparing the responses of Confucius and Socrates in these passages in particular. (shrink)