Mitochondria can change their shape from discrete isolated organelles to a large continuous reticulum. The cellular advantages underlying these fused networks are still incompletely understood. In this paper, we describe and compare hypotheses regarding the function of mitochondrial networks. We use mathematical and physical tools both to investigate existing hypotheses and to generate new ones, and we suggest experimental and modelling strategies. Among the novel insights we underline from this work are the possibilities that (i) selective mitophagy is not required (...) for quality control because selective fusion is sufficient; (ii) increased connectivity may have non‐linear effects on the diffusion rate of proteins; and (iii) fused networks can act to dampen biochemical fluctuations. We hope to convey to the reader that quantitative approaches can drive advances in the understanding of the physiological advantage of these morphological changes. (shrink)

Heterogeneity in mitochondrial content has been previously suggested as a major contributor to cellular noise, with multiple studies indicating its direct involvement in biomedically important cellular phenomena. A recently published dataset explored the connection between mitochondrial functionality and cell physiology, where a non‐linearity between mitochondrial functionality and cell size was found. Using mathematical models, we suggest that a combination of metabolic scaling and a simple model of cell death may account for these observations. However, our findings also suggest the existence (...) of alternative competing hypotheses, such as a non‐linearity between cell death and cell size. While we find that the proposed non‐linear coupling between mitochondrial functionality and cell size provides a compelling alternative to previous attempts to link mitochondrial heterogeneity and cell physiology, we emphasise the need to account for alternative causal variables, including cell cycle, size, mitochondrial density and death, in future studies of mitochondrial physiology. (shrink)

Ethical decision-making frameworks assist in identifying the issues at stake in a particular setting and thinking through, in a methodical manner, the ethical issues that require consideration as well as the values that need to be considered and promoted. Decisions made about the use, sharing, and re-use of big data are complex and laden with values. This paper sets out an Ethics Framework for Big Data in Health and Research developed by a working group convened by the Science, Health and (...) Policy-relevant Ethics in Singapore Initiative. It presents the aim and rationale for this framework supported by the underlying ethical concerns that relate to all health and research contexts. It also describes a set of substantive and procedural values that can be weighed up in addressing these concerns, and a step-by-step process for identifying, considering, and resolving the ethical issues arising from big data uses in health and research. This Framework is subsequently applied in the papers published in this Special Issue. These papers each address one of six domains where big data is currently employed: openness in big data and data repositories, precision medicine and big data, real-world data to generate evidence about healthcare interventions, AI-assisted decision-making in healthcare, public-private partnerships in healthcare and research, and cross-sectoral big data. (shrink)

Randomized controlled trial trial designs exist on an explanatory-pragmatic spectrum, depending on the degree to which a study aims to address a question of efficacy or effectiveness. As conceptualized by Schwartz and Lellouch in 1967, an explanatory approach to trial design emphasizes hypothesis testing about the mechanisms of action of treatments under ideal conditions, whereas a pragmatic approach emphasizes testing effectiveness of two or more available treatments in real-world conditions. Interest in, and the number of, pragmatic trials has grown substantially (...) in recent years, with increased recognition by funders and stakeholders worldwide of the need for credible evidence to inform clinical decision-making. This increase has been accompanied by the onset of learning healthcare systems, as well as an increasing focus on patient-oriented research. However, pragmatic trials have ethical challenges that have not yet been identified or adequately characterized. The present study aims to explore the views of key stakeholders with respect to ethical issues raised by the design and conduct of pragmatic trials. It is embedded within a large, four-year project that seeks to develop guidance for the ethical design and conduct of pragmatic trials. As a first step, this study will address important gaps in the current empirical literature with respect to identifying a comprehensive range of ethical issues arising from the design and conduct of pragmatic trials. By opening up a broad range of topics for consideration within our parallel ethical analysis, we will extend the current debate, which has largely emphasized issues of consent, to the range of ethical considerations that may flow from specific design choices. Semi-structured interviews with key stakeholders, across multiple jurisdictions, identified based on their known experience and/or expertise with pragmatic trials. We expect that the study outputs will be of interest to a wide range of knowledge users including trialists, ethicists, research ethics committees, journal editors, regulators, healthcare policymakers, research funders and patient groups. All publications will adhere to the Tri-Agency Open Access Policy on Publications. (shrink)

Philosophical discussion of the topic of intentional agency has often focused on questions about the nature of the events which are intentional actions. This event-oriented approach cannot yield an adequate account of human agency because it cannot accommodate negative acts, or acts of omission. Agents may act intentionally by omitting to act, but many such acts of omission cannot be identified with any event consisting of a bodily movement. This dissertation is an attempt to develop an account of agency which (...) can accommodate acts of omission. In the course of this, generally accepted views about the causal powers of agents, the ontology of action, the relation between an intention and the act which realizes it and the abilities exercised in acting are challenged. In Chapter One it is argued that causation by acts of omission cannot be explicated in terms of event causation and that the abilities which an agent exercises in intentionally omitting must be analyzed as second order abilities. Views according to which acts of omission are in some way constituted by positive actions are surveyed and criticized in Chapter Two. It is claimed that an agent omits to act by forming a negative intention, but this mental act is not identical to the act of omission. Acts of omission are states of affairs which obtain or facts and are not events. In Chapter Three it is shown that certain positive non-basic acts like killings also cannot be identified with any event because no event could have the requisite temporal and causal properties. Two important differences between positive and negative acts are identified in Chapter Four. The relation between a positive intention and behavior which realizes it is a causal one, but negative intentions do not cause the behavior which realizes them. A person may perform a positive action and may be responsible for this even though he lacks the ability to refrain from doing so, but to omit to perform some action and to be responsible for this, a person must have the ability to perform it. (shrink)

This collection, the first of its kind, brings together specially commissioned academic essays to mark fifty years since the death of John Kennedy Toole.

The attitudes of patients' to consent have changed over the years, but there has been little systematic study of the attitudes of anaesthetists and surgeons in this process. We aimed to describe observations made on the attitudes of medical professionals working in the UK to issues surrounding informed consent.

Prefrontal cortex is dysregulated in women with restricting anorexia nervosa . It is not known whether appetitive non-conscious stimuli bias cognitive responses in those with RAN. Thirteen women with RAN and 20 healthy controls completed a dorsolateral PFC working memory task and an anterior cingulate cortex conflict task, while masked subliminal food, aversive and neutral images were presented. During the DLPFC task, accuracy was higher in the RAN compared to the HC group, but superior performance was compromised when subliminal food (...) stimuli were presented: errors positively correlated with self-reported trait anxiety in the RAN group. These effects were not observed in the ACC task. Appetitive activation is intact and anxiogenic in women with RAN, and non-consciously interacts with working memory processes associated with the DLPFC. This interaction mechanism may underlie cognitive inhibition of appetitive processes that are anxiety inducing, in people with AN. (shrink)

As predicted by Duverger’s Law, the UK has two-party competition in each electoral district. However, there can be different patterns of two-party competition in different districts (currently there are five), so that there have usually been more than two effective parties in the Commons. Since 1874 it has always contained parties fighting seats in only one of the non-English parts of the Union. These parties wish to change the Union by strengthening, weakening, or dissolving it. By calculating the Penrose power (...) index for all parties in the House of Commons for all General Elections since 1874, we identify the occasions on which a party that wished to modify the Union was pivotal. We explain various acts (e.g, the Crofters Act 1886; the first three Irish Home Rule Bills; the Parliament Act 1911) and non-acts (e.g. the failure to enact female suffrage before 1914) by reference to the Penrose indices of the non-English parties. The indices also explain how and why policy towards Scotland, Wales and Northern Ireland changed, and did not change, in the 1970s. (shrink)

R. G. Collingwood's philosophical work is marked both by its compelling critique of scientific experience and by an unresolved tension between the claims of philosophy and the claims of history. The three works under consideration here, Speculum Mentis, Essay on Philosophical Method, and Essay on Metaphysics, comprise a systematic expression of the character of human understanding in terms of its open-ended, dialectical character, and a sustained critique of the scientific conception of human knowledge as a denial of that character.

The Varieties of British Political Thought 1500?1800 edited by J. G. A. Pocock with the assistance of Gordon J. Schochet and Lois G. Schwoerer, Cambridge, Cambridge University Press, in association with the Folger Institute, Washington D.C., 1993, pp. 373 + x, ISBN 0 521 443776, £40.00 $59.95.

Jeffery et al. accurately identify the importance of developing an understanding of spatial reference frames in a three-dimensional world. We examine human spatial cognition via a unique paradigm that investigates the role of saliency and adjusting reference frames. This includes work with adults, typically developing children, and children who develop non-typically (e.g., those with autism).

In the article art forms of utopian ideas embodiment in the novels of the Scottish writer I. Banks are considered. Utopian narratives are found both in the science-fiction cycle devoted to the civilization of Culture and in the novel "Business". Art modeling of the fundamental strategies of the society development characteristic for the New time, reveals their internal inconsistencies. Preindustrial, patriarchal living forms are offered instead. Novels by I. Banks visually demonstrate the feature of modern public consciousness and the absence (...) of ideal future representations. In the article fantastic and realistic I. Banks’ novels are compared from the point of this utopian ideal. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:IntroductionPiers H.G. StephensThis special issue of Ethics and the Environment is dedicated to the philosophical contributions of our founding editor, Victoria Davion, who launched the journal in 1996 and edited it until shortly before her death in November 2017. Vicky was a pioneering figure in ecofeminist philosophy, as well as being both the first woman to become a full professor and the first to be chair of the Philosophy (...) Department here at the University of Georgia. Naturally we have endeavored to give her a suitable tribute in this issue, which we hope you will appreciate.In addition to these achievements, Vicky developed and practiced a pedagogy that consistently complemented her philosophical perspective, and in the issue's opening piece, Cecilia Herles reflects personally on the enduring legacy and influence of Vicky Davion's teaching work, and the rich heritage that has flowed out of it for her students, encouraging egalitarian dialogue, interdisciplinarity, and a practicality that extended beyond the University and into the wider community. It is surely appropriate to begin our special issue with such an appreciation of the ways that Vicky touched and lifted up so many lives.These reflections are built upon in Chaone Mallory's essay, which takes Davion's key essay "Is Ecofeminism Feminist?" as its touchstone, examining that essay's vital influence on scholarship and activism as well as its key role in defining contemporary ecofeminism itself. Drawing upon Davion's arguments, Mallory tracks a series of vital questions for the development of the field. She demonstrates how Davion's early critical insights have helped sort the wheat from the chaff in dealing with concerns such as spirituality, irrationality, essentialism, and sexism within environmentalism, concerns that made ecofeminism questionable in some feminists' eyes, and she concludes with a positive exposition as to why "all feminisms, whether named this or not, should in some sense, be eco."From here we move to Ronnie Hawkins' extensive and detailed application of Davion's work to the neurobiological, cultural, and axiological roots of our contemporary ecological situation, in which Hawkins invokes [End Page 1] and applies the insights of Davion's 2002 essay "Anthropocentrism, Artificial Intelligence, and Moral Network Theory: An Ecofeminist Perspective." Drawing upon Davion's inventive use of Val Plumwood's account of dualisms, Hawkins stresses Davion's pioneering work in avoiding the reason/nature dualistic fracture, and uses this work to critique the predominant current discourses of AI and neuroscience, in the process further expounding Davion's critiques of anthropocentrism and logocentrism. Cashing out the wider implications of Davion's perspective for our models of the mind, Hawkins connects these to Iain McGilchrist's recent work on the neuropsychology of perception and morality, arguing that this new account of the interaction of the two cerebral hemispheres and their role in generating an orientation to the world for cognition and valuing is consistent with Davion's insights, and can both help explain the environmental failings of modern Western culture and give support for non-instrumentalizing and nonanthropocentric alternatives.Finally, Trish Glazebrook and Emmanuela Opoku offer an extended ecofeminist examination of the roles, significance, dangers, and current status of environmental protectors in contemporary global environmental politics. In a paper dedicated to Davion that addresses many of her concerns with the interlocking character of forms of oppression, they systematically investigate and elucidate the importance of environmental protectors, the struggles that they engage in, the increasing threats of violence that they face, and their significance in the fight against climate change, ultimately arguing that the UN should extend explicit protection to land and environmental defenders under its human rights umbrella.We think these contributions are a fitting tribute to our founding editor, and offer you this special issue with the wish that her legacy will endure. [End Page 2]Copyright © 2018 The Trustees of Indiana University... (shrink)

Lee McIntyre Hakikat-Sonrası (Post-Truth, 2018) adlı kitabında, hakikat-sonrası (post-truth) kavramını pazarlama ve televizyon dünyalarındaki tarihsel kökenlerine ve davranışsal psikolojideki kaynaklara dayanarak düşünsel bir kökene bağlar. McIntyre, bu kavramın yalnızca epistemolojik bir sorun olduğunu öne sürer. Bu makalede; ilk olarak hakikat-sonrası kavramı ile hakikatin bağdaşım kuramı arasında benzerlikler belirtilerek ortaya çıkan ortak epistemolojik sorunlar incelenecektir. Daha sonra, kişiselleştirme teknolojileri ve bunların istenmeyen sonuçları olan yankı odası, filtreleme baloncuğu ve siber-balkanlaştırma ile Althusser’in devletin ideolojik aygıtları arasında bir koşutluk kurularak (...) class='Hi'>McIntyre’ın yaklaşımı sorunsallaştırılacaktır. Dahası, söz konusu teknolojiler bireyleri birer üretici-tüketiciye (prosumer) dönüştürdüğü için hakikat-sonrası kavramının hem teorik hem de pratik felsefenin alanına girmesiyle aslında ideoloji kavramına karşılık gelen bir yeniyapımdan (neologism) fazlası olmadığı ileri sürülecektir. (shrink)

In this article, we try to argue, against McIntyre’s proposal in How to talk to a science denier, that there is a relevant difference between various forms of science denialism. Specifically, we contend that there is a significant distinction to be made between those forms of denialism which deny the existence of an expert consensus (the model of which is the strategy of the tobacco companies in the 1950s) and those which deny the probatory value of such expert consensus (...) (on the basis, e.g., of conspiracy theories involving scientists). While McIntyre and others advocate for the value of communicating consensus as an effective and perfectly rational strategy against those forms of denialism which deceivingly deny the existence of scientific agreement, we argue that this approach becomes question-begging against those which deny its probatory value. Accordingly, then, we object to McIntyre’s characterization that “all science denial is basically the same” and suggest a more nuanced understanding of the phenomenon. (shrink)

Against theses of Bernard Williams and Bas C. van Fraassen, it is argued that there are no facts about moral dilemmas, characterizable independently of any moral theory. It is further argued that any adequate theory which denies that there are genuine moral dilemmas must provide a convincing account of how and why moral agents take themselves to be in dilemmatic situations. The ability of rationalist theories, which deny that genuine moral dilemmas occur, to provide such account is examined. Aquinas's contribution (...) receives particular attention. (shrink)

Heidegger is now widely recognized as one of the most influential and controversial philosophers of the twentieth century, yet much of his later philosophy remains shrouded in confusion and controversy. Restoring Heidegger's understanding of metaphysics as 'ontotheology' to its rightful place at the center of his later thought, this book demonstrates the depth and significance of his controversial critique of technology, his appalling misadventure with Nazism, his prescient critique of the university, and his important philosophical suggestions for the future of (...) higher education. It will be required reading for those seeking to understand the relationship between Heidegger's philosophy and National Socialism, as well as the continuing relevance of his work. (shrink)

Heidegger, Art, and Postmodernity offers a radical new interpretation of Heidegger's later philosophy, developing his argument that art can help lead humanity beyond the nihilistic ontotheology of the modern age. Providing pathbreaking readings of Heidegger's 'The Origin of the Work of Art' and his notoriously difficult Contributions to Philosophy, this book explains precisely what postmodernity meant for Heidegger, the greatest philosophical critic of modernity, and what it could still mean for us today. Exploring these issues, Iain D. Thomson examines (...) several postmodern works of art, including music, literature, painting and even comic books, from a post-Heideggerian perspective. Clearly written and accessible, this book will help readers gain a deeper understanding of Heidegger and his relation to postmodern theory, popular culture and art. (shrink)

The digitisation of academic journals has created the technical possibility that research can be made available to any interested party free of charge. This possibility has been undermined by the proprietary control that commercial publishers exercise over the majority of this material. The control of commercial publishers over publicly-funded research has been criticised by charitable bodies, politicians and academics themselves. While the existing critical literature on academic publishers has considerable value, it fails to link questions of control within the journal-industry (...) to the wider restructuring of economic and social relations that has taken place over the last three decades. This article seeks to complement this literature by highlighting how broader profitability pressures and the subsequent attempts by state-managers to expand the social space for capitalist accumulation have structured the development of the journal-industry. (shrink)