New fetal therapies offer important prospects for improving health. However, having to consider both the fetus and the pregnant woman makes the risk–benefit analysis of fetal therapy trials challenging. Regulatory guidance is limited, and proposed ethical frameworks are overly restrictive or permissive. We propose a new ethical framework for fetal therapy research. First, we argue that considering only biomedical benefits fails to capture all relevant interests. Thus, we endorse expanding the considered benefits to include evidence-based psychosocial effects of fetal therapies. (...) Second, we reject the commonly proposed categorical risk and/or benefit thresholds for assessing fetal therapy research. Instead, we propose that the individual risks for the pregnant woman and the fetus should be justified by the benefits for them and the study’s social value. Studies that meet this overall proportionality criterion but have mildly unfavorable risk–benefit ratios for pregnant women and/or fetuses may be acceptable. (shrink)

This article analyses the challenges for the strategies and practices of transformational development in a changing context. This reflection is based on contributions received during the process of dialogues and regional consultations, realised from August 2012 until March 2014, of the ACT Alliance, an international coalition of churches and faith-based organisations working in the areas of humanitarian response, development and advocacy. The main processes that affect the changing development context are addressed, such as the ongoing globalisation as well as the (...) consequences, mainly regarding the shrinking space for civil society. It discusses the concepts of human development and of transformational development, based on a people-centred development vision, a human rights-based approach and advocacy, which addresses the root causes and effects of poverty, inequality and injustice. Transformational development practices, from Latin America, are presented and analysed. The article concludes that the changing development context also offers opportunities, especially regarding regional and global alliances of FBOs, civil society organisations and of social movements. (shrink)

Agency without Actors? New Approaches to collective Action is rethinking a key issue in social theory and research: the question of agency. The history of sociological thought is deeply intertwined with the discourse of human agency as an effect of social relations. In most recent discussions the role of non-humans gains a substantial impact. Consequently the book asks: Are nonhumans active, do they have agency? And if so: how and in what different ways? The volume offers a critical state-of-the-art debate (...) of internationally and nationally leading scholars within Sociology, Social Anthropology and STS on agency (Latour, Law, Michael, Rammert etc.). It fosters the productive exchange of empirical settings and theoretical views by outlining a wide range of novel accounts that link human and non-human agency. It tries to understand social-technical, political and environmental networks as different forms of agency that produce discrete and identifiable entities like humans, animals, technical artifacts. It also asks how different types of (often conflicting) agency and agents actors are distinguished in practice, how they are maintained and how they interfere with each other. (shrink)

The Planteome project provides a suite of reference and species-specific ontologies for plants and annotations to genes and phenotypes. Ontologies serve as common standards for semantic integration of a large and growing corpus of plant genomics, phenomics and genetics data. The reference ontologies include the Plant Ontology, Plant Trait Ontology, and the Plant Experimental Conditions Ontology developed by the Planteome project, along with the Gene Ontology, Chemical Entities of Biological Interest, Phenotype and Attribute Ontology, and others. The project also provides (...) access to species-specific Crop Ontologies developed by various plant breeding and research communities from around the world. We provide integrated data on plant traits, phenotypes, and gene function and expression from 95 plant taxa, annotated with reference ontology terms. (shrink)

New fetal therapies offer important prospects for improving health. However, having to consider both the fetus and the pregnant woman makes the risk–benefit analysis of fetal therapy trials challenging. Regulatory guidance is limited, and proposed ethical frameworks are overly restrictive or permissive. We propose a new ethical framework for fetal therapy research. First, we argue that considering only biomedical benefits fails to capture all relevant interests. Thus, we endorse expanding the considered benefits to include evidence-based psychosocial effects of fetal therapies. (...) Second, we reject the commonly proposed categorical risk and/or benefit thresholds for assessing fetal therapy research. Instead, we propose that the individual risks for the pregnant woman and the fetus should be justified by the benefits for them and the study’s social value. Studies that meet this overall proportionality criterion but have mildly unfavorable risk–benefit ratios for pregnant women and/or fetuses may be acceptable. (shrink)

About one third of patients with epilepsy have seizures refractory to the medical treatment. Electrical stimulation mapping is the gold standard for the identification of “eloquent” areas prior to resection of epileptogenic tissue. However, it is time-consuming and may cause undesired side effects. Broadband gamma activity recorded with extraoperative electrocorticography during cognitive tasks may be an alternative to ESM but until now has not proven of definitive clinical value. Considering their role in cognition, the alpha and beta bands could further (...) improve the identification of eloquent cortex. We compared gamma, alpha and beta activity, and their combinations for the identification of eloquent cortical areas defined by ESM. Ten patients with intractable focal epilepsy participated in a delayed-match-to-sample task, where syllable sounds were compared to visually presented letters. We used a generalized linear model approach to find the optimal weighting of each band for predicting ESM-defined categories and estimated the diagnostic ability by calculating the area under the receiver operating characteristic curve. Gamma activity increased more in eloquent than in non-eloquent areas, whereas alpha and beta power decreased more in eloquent areas. Diagnostic ability of each band was close to 0.7 for all bands but depended on multiple factors including the time period of the cognitive task, the location of the electrodes and the patient’s degree of attention to the stimulus. We show that diagnostic ability can be increased by 3–5% by combining gamma and alpha and by 7.5–11% when gamma and beta were combined. We then show how ECoG power modulation from cognitive testing can be used to map the probability of eloquence in individual patients and how this probability map can be used in clinical settings to optimize ESM planning. We conclude that the combination of gamma and beta power modulation during cognitive testing can contribute to the identification of eloquent areas prior to ESM in patients with refractory focal epilepsy. (shrink)

Mechanistic models are built using knowledge as the primary information source, with well-established biological and physical laws determining the causal relationships within the model. Once the causal structure of the model is determined, parameters must be defined in order to accurately reproduce relevant data. Determining parameters and their values is particularly challenging in the case of models of pathophysiology, for which data for calibration is sparse. Multiple data sources might be required, and data may not be in a uniform or (...) desirable format. We describe a calibration strategy to address the challenges of scarcity and heterogeneity of calibration data. Our strategy focuses on parameters whose initial values cannot be easily derived from the literature, and our goal is to determine the values of these parameters via calibration with constraints set by relevant data. When combined with a covariance matrix adaptation evolution strategy, this step-by-step approach can be applied to a wide range of biological models. We describe a stepwise, integrative and iterative approach to multiscale mechanistic model calibration, and provide an example of calibrating a pathophysiological lung adenocarcinoma model. Using the approach described here we illustrate the successful calibration of a complex knowledge-based mechanistic model using only the limited heterogeneous datasets publicly available in the literature. (shrink)

Social interactions of autistic and non-autistic persons are intriguing. In all sorts of situations people with autism are part of the daily life of those around them. Such interactions exist despite the lack of familiar ways of attuning to one another. In Autistic Company, the anthropologist and philosopher Ruud Hendriks—himself trained as a care worker for young people with autism—investigates what alternative means are sometimes found by autistic and non-autistic people to establish a shared existence. Unprecedented in scholarly work (...) on autism, the book also reflects on how to talk about these unusual ways of getting on together. Drawing on methods from both the arts and the social sciences, this study covers very diverse sources, ranging from literary works to factual writing on autism in science and advisory literature, and from autobiographical accounts to ethnographic observations in a home for autistic people. “Putting familiar concepts to a test, Autistic Company wrenches and fiddles with the very distinctions that constitute our sense of self. By doing so, Hendriks succeeds in getting closer both to autistic and non-autistic extremes, showing how thin the division between us and them really is.” -L.W. Nauta in Krisis. (shrink)

It is well-known that Plato’s Republic introduces a tripartition of the incarnate human soul; yet quite how to interpret his ‘parts’ 1 is debated. On a strong reading, they are psychological subjects – much as we take ourselves to be, but homunculi, not homines. On a weak reading, they are something less paradoxical: aspects of ourselves, identified by characteristic mental states, dispositional and occurrent, that tend to come into conflict. Christopher Bobonich supports the strong reading in his Plato’s Utopia Recast: (...) His Later Ethics and Politics. In his The Brute Within: Appetitive Desire in Plato and Aristotle, Hendrik Lorenz agrees with Bobonich that the parts of the soul are ‘the subjects or bearers of psychological states’. Any ascription to my Mental Conflict of the opposed, weak view needs qualification: my Plato is highly ambivalent.2 But my intention here is less to defend an earlier self – though I predict failing to escape it – than to reconsider tripartition in the Republic in the light of Bobonich’s virtuosity and Lorenz’s lucidity. They persuade me of the inexhaustibility of the text, notably within Book 4 from 436 to 439. About these pages we may indeed disagree: they find them decisive in favour of their view, as I don’t. When Socrates remarks, ‘Let us have our understanding still more precise, lest as we proceed we become involved in dispute’, he was not anticipating the dissensions of interpreters. (shrink)

The revised edition contains a new chapter which provides an elegant description of the semantics. The various classes of lambda calculus models are described in a uniform manner. Some didactical improvements have been made to this edition. An example of a simple model is given and then the general theory (of categorical models) is developed. Indications are given of those parts of the book which can be used to form a coherent course.

Conflicts in Interpretation applies novel methods of constraint interaction, derived from connectionist theories and implemented in linguistics within the framework of Optimality Theory, to core semantic and pragmatic issues such as polysemy, negation, (in) definiteness, focus, anaphora, and rhetorical structure. It explores the hypothesis that a natural language grammar is a set of potentially conflicting constraints on forms and meanings. Moreover, it hypothesizes that competent language users not only optimize from an input form to the optimal output meaning for this (...) form, or vice versa, but also consider the opposite direction of optimization, thus taking into account the speaker as a hearer and taking into account the hearer as a speaker. The book aims to show that such a bidirectional constraint-based grammar sheds new light on the relation between form and meaning, within a sentence as well as across sentence boundaries, within a single language as well as across languages, and within competent adult language users as well as during language development. An important dimension of the book is the structured investigation of issues at the interface of semantics with syntax and pragmatics, such as the effects of distinguishing between speaker's perspective and hearer's perspective in comprehension and production, stable and instable patterns of form and meaning across languages, and the development of a coherent pattern of form and meaning in children. Conflicts in Interpretation will be of interest to any researcher or advanced student in linguistics, cognitive science, language typology, or psycholinguistics who is interested in the capacity of our human mind to map meaning onto form, and form onto meaning. (shrink)

The pivotal problem of comorbidity research lies in the psychometric foundation it rests on, that is, latent variable theory, in which a mental disorder is viewed as a latent variable that causes a constellation of symptoms. From this perspective, comorbidity is a (bi)directional relationship between multiple latent variables. We argue that such a latent variable perspective encounters serious problems in the study of comorbidity, and offer a radically different conceptualization in terms of a network approach, where comorbidity is hypothesized to (...) arise from direct relations between symptoms of multiple disorders. We propose a method to visualize comorbidity networks and, based on an empirical network for major depression and generalized anxiety, we argue that this approach generates realistic hypotheses about pathways to comorbidity, overlapping symptoms, and diagnostic boundaries, that are not naturally accommodated by latent variable models: Some pathways to comorbidity through the symptom space are more likely than others; those pathways generally have the same direction (i.e., from symptoms of one disorder to symptoms of the other); overlapping symptoms play an important role in comorbidity; and boundaries between diagnostic categories are necessarily fuzzy. (shrink)

Things and Their Place in Theories Our talk of external things, our very notion of things, is just a conceptual apparatus that helps us to foresee and ...

The building of a global model of carcinogenesis is one of modern biology’s greatest challenges. The traditional somatic mutation theory is now supplemented by a new approach, called the Tissue Organization Field Theory. According to TOFT, the original source of cancer is loss of tissue organization rather than genetic mutations. In this paper, we study the argumentative strategy used by the advocates of TOFT to impose their view. In particular, we criticize their claim of incompatibility used to justify the necessity (...) to definitively reject SMT. First, we note that since it is difficult to build a non-ambiguous experimental demonstration of the superiority of TOFT, its partisans add epistemological and metaphysical arguments to the debate. This argumentative strategy allows them to defend the necessity of a paradigm shift, with TOFT superseding SMT. To do so, they introduce a notion of incompatibility, which they actually use as the Kuhnian notion of incommensurability. To justify this so-called incompatibility between the two theories of cancer, they move the debate to a metaphysical ground by assimilating the controversy to a fundamental opposition between reductionism and organicism. We show here that this argumentative strategy is specious, because it does not demonstrate clearly that TOFT is an organicist theory. Since it shares with SMT its vocabulary, its ontology and its methodology, it appears that a claim of incompatibility based on this metaphysical plan is not fully justified in the present state of the debate. We conclude that it is more cogent to argue that the two theories are compatible, both biologically and metaphysically. We propose to consider that TOFT and SMT describe two distinct and compatible causal pathways to carcinogenesis. This view is coherent with the existence of integrative approaches, and suggests that they have a higher epistemic value than the two theories taken separately. (shrink)

In this paper, we first classify different types of second opinions and evaluate the ethical and epistemological implications of providing those in a clinical context. Second, we discuss the issue of how artificial intelligent could replace the human cognitive labour of providing such second opinion and find that several AI reach the levels of accuracy and efficiency needed to clarify their use an urgent ethical issue. Third, we outline the normative conditions of how AI may be used as second opinion (...) in clinical processes, weighing the benefits of its efficiency against concerns of responsibility attribution. Fourth, we provide a ‘rule of disagreement’ that fulfils these conditions while retaining some of the benefits of expanding the use of AI-based decision support systems in clinical contexts. This is because the rule of disagreement proposes to use AI as much as possible, but retain the ability to use human second opinions to resolve disagreements between AI and physician-in-charge. Fifth, we discuss some counterarguments. (shrink)

This paper is devoted to computer modelling of the development and regeneration of multicellular biological structures. Some species are able to regenerate parts of their body after amputation damage, but the global rules governing cooperative cell behaviour during morphogenesis are not known. Here, we consider a simplified model organism, which consists of tissues formed around special cells that can be interpreted as stem cells. We assume that stem cells communicate with each other by a set of signals, and that the (...) values of these signals depend on the distance between cells. Thus the signal distribution characterizes location of stem cells. If the signal distribution is changed, then the difference between the initial and the current signal distribution affects the behaviour of stem cells—e.g. as a result of an amputation of a part of tissue the signal distribution changes which stimulates stem cells to migrate to new locations, appropriate for regeneration of the proper pattern. Moreover, as stem cells divide and form tissues around them, they control the form and the size of regenerating tissues. This two-level organization of the model organism, with global regulation of stem cells and local regulation of tissues, allows its reproducible development and regeneration. (shrink)

Systems biology is today such a widespread discipline that it becomes difficult to propose a clear definition of what it really is. For some, it remains restricted to the genomic field. For many, it designates the integrated approach or the corpus of computational methods employed to handle the vast amount of biological or medical data and investigate the complexity of the living. Although defining systems biology might be difficult, on the other hand its purpose is clear: systems biology, with its (...) emerging subfields systems medicine and systems pharmacology, clearly aims at making sense of complex observations/experimental and clinical datasets to improve our understanding of diseases and their treatments without putting aside the context in which they appear and develop. In this short review, we aim to specifically focus on these new subfields with the new theoretical tools and approaches that were developed in the context of cancer. Systems pharmacology and medicine now give hope for major improvements in cancer therapy, making personalized medicine closer to reality. As we will see, the current challenge is to be able to improve the clinical practice according to the paradigm shift of systems sciences. (shrink)

The field of synthetic biology is looking forward engineering framework for safely designing reliable de-novo biological functions. In this undertaking, Computer-Aided-Design environments should play a central role for facilitating the design. Although, CAD environment is widely used to engineer artificial systems the application in synthetic biology is still in its infancy. In this article we address the problem of the design of a high level language which at the core of CAD environment. More specifically the Gubs language is a specification (...) language used to describe the observations of the expected behaviour. The compiler appropriately selects components such that the observation of the synthetic biological function resulting to their assembly complies to the programmed behaviour. (shrink)

The project 'Facing Forward' started with a collaboration between five institutions: the Stedelijk Museum Amsterdam, the Amsterdam School for Cultural Analysis at the University of Amsterdam, De Appel arts centre, W139, the Stedelijk Museum Bureau Amsterdam and the art magazine Metroplis M. Having previously organized the lecture series and publications 'Right About Now: Art & Theory in the 1990s' (2005/2006) and 'Now is the Time: Art & Theory in the 21st Century' (2008/2009), the organizing committee decided to take the final (...) step in this timeline and turn its attention to the far horizon. Informed by a shared interest in the role that history, speculation, and utopianism play in the field of contemporary art and design (as well as the larger context of global, socio-economic and political developments), a selection of seven themes emerged from the conversations of the initial organizers. These would eventually shape the seven lecture and discussions events - collected in this volume of essays - publicized under the banner Art & Theory From a Future Perspective. A great number of internationally renowned speakers were invited to reflect on the proposed themes during often sold-out events, which were presented at the Oude Lutherse Kerk in Amsterdam in 2011/2012. Yet, however compelling our desire as organizers to go beyond the framework of contemporary events and the current interest, well-nigh obsession, with history, it is obviously an illusion to think that we can escape the past by means of a turn towards the future."--Page 8. (shrink)

Inleidend overzicht van de wetenschapsfilosofische basisproblemen van de rechtswetenschap.

Descartes' works were not allowed to be read at Leiden University, even his name could not be pronounced. Read the compelling story about how his pupil Johannes de Raey has had the opportunity to preach Descartes fully in philosophy, but also in medicine, in a hostile anti-Cartesian climate during 20 years (1647-1668). This book is not only meant for philosophers and medical historians, but for all who want to take a look at the extensive menu of Cartesian cuisine. The 17th-century (...) philosopher René Descartes turned established science upside down by doubting all certainties. His critical mind rejected statements that could not be proven by the Ratio. The Ratio was the metaphor for the roots, the physics for the trunk and the medicine for the branches and leaves of the Cartesian tree. This premise was directly opposed to the established aristotelian theory in which observation formed the basis of knowledge. De Raey, who once called Descartes his best student, synthesized a hybrid model of the old Aristotelian and the new Cartesian concept. From 1658 to 1662 he gave private lessons in medicine at Leiden University and tried to use his model as a basis for explaining human physiology. Until now, nothing was known about the content of these lectures. The author recently found a dispute. It is a new dish on the Cartesian menu. (shrink)

Although Darwinian concepts have largely been banned from the social sciences of the last century, they have recently seen a revival in several disciplines such as sociology, anthropology, or economics. Most of the current proponents of evolutionary theorizing in the social sciences avoid references to the older literature on social evolution. On that background, this article presents a contribution to Darwinist thinking in early American sociology that has mainly been overlooked in the literature. As the leading figure of the Human (...) Ecology Approach, which was established during the 1920s and 1930s, Robert Ezra Park drew heavily on evolutionary concepts to explain human evolution. A systematic presentation of these concepts in the light of the modern discussion on sociocultural evolution is given, followed by a conclusion about what can be learned from Park today. (shrink)

Hendrik Lorenz presents a comprehensive study of Plato's and Aristotle's conceptions of non-rational desire. They see this as something that humans share with animals, and which aims primarily at the pleasures of food, drink, and sex. Lorenz explores the cognitive resources that both philosophers make available for the explanation of such desires, and what they take rationality to add to the motivational structure of human beings. In doing so, he finds conceptions of the mind that are coherent and deeply integrated (...) with both philosophers' views about such topics as the relation between body and soul, or the nature of the virtues. (shrink)

This paper explores the role and resolution of disagreements between physicians and their diagnostic AI-based decision support systems. With an ever-growing number of applications for these independently operating diagnostic tools, it becomes less and less clear what a physician ought to do in case their diagnosis is in faultless conflict with the results of the DSS. The consequences of such uncertainty can ultimately lead to effects detrimental to the intended purpose of such machines, e.g. by shifting the burden of proof (...) towards a physician. Thus, we require normative clarity for integrating these machines without affecting established, trusted, and relied upon workflows. In reconstructing different causes of conflicts between physicians and their AI-based tools—inspired by the approach of “meaningful human control” over autonomous systems and the challenges to resolve them—we will delineate normative conditions for “meaningful disagreements”. These incorporate the potential of DSS to take on more tasks and outline how the moral responsibility of a physician can be preserved in an increasingly automated clinical work environment. (shrink)

This paper wants to shed light on the way the philosophical school of Stoicsm in Greco-Roman antiquity has dealt with the relationship of men and nature by pointing out to some of the key texts in which these issues are mentioned. Although the modern concept of sustainability or environmental protection did not really exist in antiquity, the Stoa was convinced that individual decisions had a direct impact on this world. Following the concept of environmental humanities, the ancient texts and authors (...) are collected as historical ideas of the multifaceted interactions between nature and men that can be fruitfully mirrored with the arguments of the current Anthropocene discourse and its focus on (post)industrialism. By doing so we might come across helpful approaches deeply rooted in our cultural heritage that we could possibly adopt and find practical answers for our age in terms of individual behaviour as well as management decisions to face the ecological and social challenges ahead. (shrink)

This book arose out of a conference organised by the Fay Gale Centre for Research on Gender at The University of Adelaide honouring Carol Bacchi's work and is intended to make that work accessible to a range of audiences. - from the ...

In this article we present a new kind of computing device that uses biochemical reactions networks as building blocks to implement logic gates. The architecture of a computing machine relies on these generic and composable building blocks, computation units, that can be used in multiple instances to perform complex boolean functions. Standard logical operations are implemented by biochemical networks, encapsulated and insulated within synthetic vesicles called protocells. These protocells are capable of exchanging energy and information with each other through transmembrane (...) electron transfer. In the paradigm of computation we propose, protoputing, a machine can solve only one problem and therefore has to be built specifically. Thus, the programming phase in the standard computing paradigm is represented in our approach by the set of assembly instructions that directs the wiring of the protocells that constitute the machine itself. To demonstrate the computing power of protocellular machines, we apply it to solve a NP-complete problem, known to be very demanding in computing power, the 3-SAT problem. We show how to program the assembly of a machine that can verify the satisfiability of a given boolean formula. Then we show how to use the massive parallelism of these machines to verify in less than 20 min all the valuations of the input variables and output a fluorescent signal when the formula is satisfiable or no signal at all otherwise. (shrink)

This article examines women who have been antinuclear activists at the Three Mile Island nuclear power plant for two decades. Qualitative interviews focus on their perceived transformations over time that are based on gender and everyday experiences. They perceive gender as both a barrier and a facilitator to activism, even after 20 years. Women describe their technological education as one strategy to overcome the barrier of gender. On the other hand, they consider the gendered role of motherhood as a primary (...) catalyst for action. In addition, they discuss individual everyday experiences focused on the health concerns for family members that influenced their political activity. Over time, women linked personal transformations with increased political understanding and involvement. (shrink)

RÉSUMÉLe mot «migrants» n'existait pas dans la langue des Hellènes; ils étaient plus familiers avec le vocable de l'exil et de l'asile. D'ailleurs, l'exil ne saurait se penser sans son corollaire, l'asile, comme le citoyen antique sans le barbare et la démocratie sans la tyrannie. À travers une métaphore située au carrefour de la fiction historique, de la philosophie politique et de la psychanalyse, cet article propose une réflexion sur l'exil comme condition fondamentale du sujet. L'exil est d'origine, car la (...) langue de l'enfance, la langue dite maternelle est d'abord une langue étrangère. L'exil intime porte la marque d'une universalité qui fonde l'expérience subjective.ABSTRACTThe word ‘migrants’ did not exist in the language of the Hellenes; they were more familiar with the terms ‘exile’ and ‘political asylum.’ Indeed, exile cannot be thought of without its corollary, political asylum, as the Ancient citizen cannot be thought of without the barbarian, and democracy without tyranny. Through a metaphor located at the crossroads of historical fiction, political philosophy and psychoanalysis, this article offers a reflection on exile as a fundamental condition of the subject. Exile is originary because the language of childhood, the so-called mother tongue, is originally a foreign language. Intimate exile bears the mark of a universality that founds subjective experience. (shrink)

Brieven van de Nederlandse filosoof (1898-1955) uit de periode 1917-1927 aan een vriend.

Lindquist et al. present a strong case for a constructionist account of emotion. First, we elaborate on the ramifications that a constructionist account of emotions might have for psychiatric disorders with emotional disturbances as core elements. Second, we reflect on similarities between Lindquist et al.'s model and recent attempts at formulating psychiatric disorders as networks of causally related symptoms.

The majority of commentators agree on one thing: Our network approach might be the prime candidate for offering a new perspective on the origins of mental disorders. In our response, we elaborate on refinements (e.g., cognitive and genetic levels) and extensions (e.g., to Axis II disorders) of the network model, as well as discuss ways to test its validity.

Inleiding tot de Duitse filosoof (1724-1804).