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)
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 the past decades, reductionism has dominated both research directions and funding policies in clinical psychology and psychiatry. The intense search for the biological basis of mental disorders, however, has not resulted in conclusive reductionist explanations of psychopathology. Recently, network models have been proposed as an alternative framework for the analysis of mental disorders, in which mental disorders arise from the causal interplay between symptoms. In this target article, we show that this conceptualization can help explain why reductionist approaches in (...) psychiatry and clinical psychology are on the wrong track. First, symptom networks preclude the identification of a common cause of symptomatology with a neurobiological condition; in symptom networks, there is no such common cause. Second, symptom network relations depend on the content of mental states and, as such, feature intentionality. Third, the strength of network relations is highly likely to depend partially on cultural and historical contexts as well as external mechanisms in the environment. Taken together, these properties suggest that, if mental disorders are indeed networks of causally related symptoms, reductionist accounts cannot achieve the level of success associated with reductionist disease models in modern medicine. As an alternative strategy, we propose to interpret network structures in terms of D. C. Dennett's notion ofreal patterns, and suggest that, instead of being reducible to a biological basis, mental disorders feature biological and psychological factors that are deeply intertwined in feedback loops. This suggests that neither psychological nor biological levels can claim causal or explanatory priority, and that a holistic research strategy is necessary for progress in the study of mental disorders. (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)
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)
The Enzymatic control reactions model was presented within the scope of fractional calculus. In order to accommodate the usual initial conditions, the fractional derivative used is in Caputo sense. The methodologies of the three analytical methods were used to derive approximate solution of the fractional nonlinear system of differential equations. Two methods use integral operator and the other one uses just an integral. Numerical results obtained exhibit biological behavior of real world problem.
Society is increasingly utilizing a firm’s social and environmental performance as a primary metric in evaluating legitimacy. As a result there is a growing scholarly need for more precise and socially relevant measures of the social impact of corporations, or corporate social impact, as opposed to broader or more firm-relevant metrics, such as financial or reputational impacts. I propose that a contingent approach, which explicitly examines the methodological fit between research scope and research method, can be a useful framework to (...) aid CSI scholars in navigating the conceptual messiness of measuring CSI. The aim of this article is to contribute a framework that can be used to effectively address questions of CSI measurement by guiding the use of appropriate research methods and design to fit a given research scope. (shrink)
Michael H. Mitias argues that friendship is a central moral value constituting an integral part of the good life and therefore deserving a prominent place in ethical theory. He consequently calls upon ethicists to make immediate and decisive adjustments toward accommodating what he regards as a neglected organic relationship between friendship and morality. This is not a fanciful amendment to our standard conception of morality but a radical proposal grounded in a unifying vision to recapture the right way of doing (...) ethics. While the assessment is compelling, and the plea well-placed, neither has been fully understood in the scholarly reception of Mitias. This paper clarifies both. What sets it apart from other reactions to Mitias is a holistic approach drawing on literary considerations as well as philosophical ones. The combined aim is to demonstrate that Mitias is not seeking simply to restore friendship to its rightful place in normative ethical theory, which is indeed the full extent of his formal mission, but that he is seeking to do so specifically within virtue ethics. This interpretation rests on a broad engagement with Mitias’s publications beyond the recent treatise often taken understandably yet erroneously to be his only work on the subject. (shrink)
Considering the persisting disagreement between the common sense philosophers and the sceptics, it seems that they are faced with a deep epistemic disagreement. Taking stock from Wittgenstein’s On Certainty, one generally thinks that deep epistemic disagreements cannot be rationally resolved. Hinge epistemology, inherited from Wittgenstein, is also considered as an illuminating detour to understand common sense epistemology. But is there really a deep epistemic disagreement between the common sense philosophers and the sceptics? Could it not be considered that they share (...) a common background? If so, is the rational resolution of their disagreement logically possible? What rational means can common sense use to convince someone of the privileged status of an epistemic principle? Relying on Reid’s, Alston’s and Lynch’s arguments, I show that common sense epistemology is a more promising approach than hinge epistemology, because it is driven by an optimism about reason in the solving of deep epistemic disagreements. (shrink)
Large sets of elements interacting locally and producing specific architectures reliably form a category that transcends the usual dividing line between biological and engineered systems. We propose to call them morphogenetically architected complex systems. While taking the emergence of properties seriously, the notion of MACS enables at the same time the design of operational means that allow controlling and even, paradoxically, programming this emergence. To demonstrate our claim, we first show that among all the self-organized systems studied in the field (...) of Artificial Life, the specificity of MACS essentially lies in the close relation between their emergent properties and functional properties. Second, we argue that to be a MACS a system does not need to display more than weak emergent properties. Third, since the notion of weak emergence is based on the possibility of simulation, whether computational or mechanistic via machines, we see MACS as good candidates to help design artificial self-architected systems but also harness and redesign living ones. (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 ...
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 classic model of blood pressure regulation by Guyton et al. set a new standard for quantitative exploration of physiological function and led to important new insights, some of which still remain the focus of debate, such as whether the kidney plays the primary role in the genesis of hypertension. Key to the success of this model was the fact that the authors made the computer code freely available and eventually provided a convivial user interface for exploration of model behavior (...) on early microcomputers. Ikeda et al. developed an offshoot of the Guyton model targeting especially the regulation of body fluids and acid–base balance; their model provides extended renal and respiratory functions and would be a good basis for further extensions. In the interest of providing a simple, useable version of Ikeda et al.’s model and to facilitate further such extensions, we present a practical implementation of the model of Ikeda et al., using the ODE solver Berkeley Madonna. (shrink)
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.
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)
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)
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)
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)
The aim of this article is to show how a tumor can modify energy substrates fluxes in the brain to support its own growth. To address this question we use a modeling approach to explain brain nutrient kinetics. In particular we set up a system of 17 equations for oxygen, lactate, glucose concentrations and cells number in the brain. We prove the existence and uniqueness of nonnegative solutions and give bounds on the solutions. We also provide numerical simulations.
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)
ABSTRACTNew Zealanders were presented with the opportunity to change the national flag and opted to retain the current New Zealand flag, despite arguments that it was unable to reflect national identity adequately. This article unpacks the particular version of national identity constructed in discourse in the infographic, Our Nation. Your Choice. which was released prior to the final referendum that determined the outcome of the Flag Consideration Project. We used Fairclough’s critical discourse analysis to examine the discursive construction of national (...) identity by the Flag Consideration Panel that oversaw the process. The authoritative assertion of national identity on behalf of New Zealanders emphasised inclusiveness and unity by acknowledging cultural diversity. Biculturalism was confined to an old understanding of New Zealand identity while the ideology of multiculturalism, not yet officially implemented, was positioned as common-sense. There was a focus on situating New Zealand in a global context to distance New Zealand from colonisation and connection to Britain. The positive, cohesive conceptualisation of New Zealand suggested that the Flag Consideration Project was, in fact, an exercise in re-positioning New Zealand in the global context, in which the national flag would represent the national brand rather than contribute to national identity. (shrink)