Annamaria Carusi

Bridging experiments, models and simulations: an integrative approach to validation in computational cardiac electrophysiology.

Computational models in physiology often integrate functional and structural information from a large range of spatiotemporal scales from the ionic to the whole organ level. Their sophistication raises both expectations and skepticism concerning how computational methods can improve our understanding of living organisms and also how they can reduce, replace, and refine animal experiments. A fundamental requirement to fulfill these expectations and achieve the full potential of computational physiology is a clear understanding of what models represent and how they can be validated. The present study aims at informing strategies for validation by elucidating the complex interrelations among experiments, models, and simulations in cardiac electrophysiology. We describe the processes, data, and knowledge involved in the construction of whole ventricular multiscale models of cardiac electrophysiology. Our analysis reveals that models, simulations, and experiments are intertwined, in an assemblage that is a system itself, namely the model-simulation-experiment (MSE) system. We argue that validation is part of the whole MSE system and is contingent upon 1) understanding and coping with sources of biovariability; 2) testing and developing robust techniques and tools as a prerequisite to conducting physiological investigations; 3) defining and adopting standards to facilitate the interoperability of experiments, models, and simulations; 4) and understanding physiological validation as an iterative process that contributes to defining the specific aspects of cardiac electrophysiology the MSE system targets, rather than being only an external test, and that this is driven by advances in experimental and computational methods and the combination of both.

Variability in cardiac electrophysiology: Using experimentally-calibrated populations of models to move beyond the single virtual physiological human paradigm.

Physiological variability manifests itself via differences in physiological function between individuals of the same species, and has crucial implications in disease progression and treatment. Despite its importance, physiological variability has traditionally been ignored in experimental and computational investigations due to averaging over samples from multiple individuals. Recently, modelling frameworks have been devised for studying mechanisms underlying physiological variability in cardiac electrophysiology and pro-arrhythmic risk under a variety of conditions and for several animal species as well as human. One such methodology exploits populations of cardiac cell models constrained with experimental data, or experimentally-calibrated populations of models. In this review, we outline the considerations behind constructing an experimentally-calibrated population of models and review the studies that have employed this approach to investigate variability in cardiac electrophysiology in physiological and pathological conditions, as well as under drug action. We also describe the methodology and compare it with alternative approaches for studying variability in cardiac electrophysiology, including cell-specific modelling approaches, sensitivity-analysis based methods, and populations-of-models frameworks that do not consider the experimental calibration step. We conclude with an outlook for the future, predicting the potential of new methodologies for patient-specific modelling extending beyond the single virtual physiological human paradigm.

From Data Archive to Ethical Labyrinth

Researchers in the social sciences are increasingly encouraged or obliged to deposit data in digital archives for greater transparency of research or for secondary use by other researchers. However, digital archives raise many ethical challenges at the institutional, disciplinary and personal level, and researchers can find themselves caught between conflicting requirements. This article considers the ethical challenges of qualitative data in particular showing what specific ethical challenges qualitative researchers face. There is generally a lack of policy or guidelines as to how to deal with digital data, or else there are conflicting requirements set by funding and academic institutions and by the law. In the face of this, researchers themselves need to be aware of the ethical and legal dimensions of their data, so that they are in the best position to enter into negotiations concerning whether and how it is archived. The options for archiving are outlined, and an interdisciplinary approach is recommended.

The Case of the Disappearing Ox: Seeing Through Digital Images to an Analysis of Ancient Texts

There are numerous settings where people examine, scrutinize and discuss the details of images in the course of their work. In most medical domains, scans and x-rays are used in the diagnosis of cases; in most areas of science, methods of visualization have been adopted to assist in the analysis of data; and images of different kinds are critical for many research fields in the social sciences and humanities. It is not surprising that recently technologies have been proposed to assist with the analysis and examination of images. In this paper, we consider requirements for technologies in a rather distinctive domain of research, the classics. Drawing upon an analysis of the detailed ways in which classicists work with digital images, we discuss the requirements for systems to support researchers in this domain, and also provide further considerations on the general development of image processing technologies and visualization techniques.There are numerous settings where people examine, scrutinize and discuss the details of images in the course of their work. In most medical domains, scans and x-rays are used in the diagnosis of cases; in most areas of science, methods of visualization have been adopted to assist in the analysis of data; and images of different kinds are critical for many research fields in the social sciences and humanities. It is not surprising that recently technologies have been proposed to assist with the analysis and examination of images. In this paper, we consider requirements for technologies in a rather distinctive domain of research, the classics. Drawing upon an analysis of the detailed ways in which classicists work with digital images, we discuss the requirements for systems to support researchers in this domain, and also provide further considerations on the general development of image processing technologies and visualization techniques.

Human-based approaches to pharmacology and cardiology: an interdisciplinary and intersectorial workshop

Both biomedical research and clinical practice rely on complex datasets for the physiological and genetic characterization of human hearts in health and disease. Given the complexity and variety of approaches and recordings, there is now growing recognition of the need to embed computational methods in cardiovascular medicine and science for analysis, integration and prediction. This paper describes a Workshop on Computational Cardiovascular Science that created an international, interdisciplinary and inter-sectorial forum to define the next steps for a human-based approach to disease supported by computational methodologies. The main ideas highlighted were (i) a shift towards human-based methodologies, spurred by advances in new in silico, in vivo, in vitro, and ex vivo techniques and the increasing acknowledgement of the limitations of animal models. (ii) Computational approaches complement, expand, bridge, and integrate in vitro, in vivo, and ex vivo experimental and clinical data and methods, and as such they are an integral part of human-based methodologies in pharmacology and medicine. (iii) The effective implementation of multi- and interdisciplinary approaches, teams, and training combining and integrating computational methods with experimental and clinical approaches across academia, industry, and healthcare settings is a priority. (iv) The human-based cross-disciplinary approach requires experts in specific methodologies and domains, who also have the capacity to communicate and collaborate across disciplines and cross-sector environments. (v) This new translational domain for human-based cardiology and pharmacology requires new partnerships supported financially and institutionally across sectors. Institutional, organizational, and social barriers must be identified, understood and overcome in each specific setting.

Retaining volunteers in volunteer computing projects

Volunteer computing projects (VCPs) have been set up by groups of scientists to recruit members of the public who are asked to donate spare capacity on their personal computers to the processing of scientific data or computationally intensive models. VCPs serve two purposes: to acquire significant computing capacity and to educate the public about science. A particular challenge for these scientists is the retention of volunteers as there is a very high drop-out rate. This paper develops recommendations for scientists and software engineers setting up or running VCPs regarding which strategies to pursue in order to improve volunteer retention rates. These recommendations are based on a qualitative study of volunteers in a VCP (climateprediction.net). A typology of volunteers has been developed, and three particularly important classes of volunteers are presented in this paper: for each type of volunteer, the particular benefits they offer to a project are described, and their motivations for continued participation in a VCP are identified and linked to particular strategies. In this way, those setting up a VCP can identify which types of volunteers they should be particularly keen to retain, and can then find recommendations to increase the retention rates of their target volunteers.

The postcolonial other as a problem for political action

Summary This article is an attempt to broach the issue of heterogeneity, recasting it as a problem for theories of postcolonialism, and for the poststructuralist theories on which they are based. Heterogeneity results in a dilemma for the theorising of reconstitutive political action: If the colonised person is seen as radically heterogeneous, s/he is inevitably either passive and incapable of acting for liberation, or the discourses which allow for resistance or emancipatory action are subject to the same critique as the discourses of imperialist domination. Where heterogeneity is conceived as a problem, but theoretically retained and affirmed, the theory becomes incoherent. This is a result of the terms in which heterogeneity has been cast in these theories. Ultimately the problem of heterogeneity as it emerges in theories of postcolonialism threatens to undermine the political dimension of these theories, and of poststructuralism.

Textual Practitioners: A Comparison of Hypertext Theory and Phenomenology of Reading.

The article is an exploration of online reading from the perspective of theories of reading and interpretation based on literary theory and the phenomenology of reading literary text. One of its aims is to show that such theories can make a contribution to our understanding of reading and to our design of online reading spaces. The precursor of this stance is the form of hypertext theory originally proposed by George Landow, which predicted radical changes in reading practices with an impact not only on literature but on education in general. The prediction has been slow to be verified and has been criticized by empirical and psychological studies. In this article, hypertext theory is compared to the phenomenology of reading linear literary text, with particular attention paid to the role played by the notion of a text, work or ‘whole’ which is constructed or produced during the course of reading. I show that the active and engaged reading predicted by hypertext theory is available in reading linear literary text, and to a higher degree than in reading hypertext, and consider ways in which the kinds of reading process which occur in reading literature can be generalized to reading for other higher education purposes. Finally, I speculate as to the range of online technologies that could be used to encourage these reading processes, and propose an alternative online reading space.

Scientific visualisations and aesthetic grounds for trust

The collaborative ‹Big Science’ approach prevalent in physics during the mid- and late-20th century is becoming more common in the life sciences. Often computationally mediated, these collaborations challenge researchers’ trust practices. Focusing on the visualisations that are often at the heart of this form of scientific practice, the paper proposes that the aesthetic aspects of these visualisations are themselves a way of securing trust. Kant’s account of aesthetic judgements in the Third Critique is drawn upon in order to show that the image-building capability of imagination, and the sensus communis, both of which are integral parts of aesthetic experience, play an important role in building and sustaining community in these forms of science. Kant’s theory shows that the aesthetic appeal of scientific visualisations is not isolated from two other dimensions of the visualisations: the cognitive-epistemic, aesthetic-stylistic and interpersonal dimensions, and that in virtue of these inter-relationships, visualisations contribute to building up the intersubjectively shared framework of agreement which is basic for trust.

THE ETHICAL WORK THAT REGULATIONS WILL NOT DO

Ethical concerns in e-social science are often raised with respect to privacy, confidentiality, anonymity and the ethical and legal requirements that govern research. In this article, the authors focus on ethical aspects of e-research that are not directly related to ethical regulatory framework or requirements. These frameworks are often couched in terms of benefits or harms that can be incurred by participants in the research. The authors shift the focus to the sources of value in terms of which benefits or harms are understood in real social situations. A central claim of this paper is that the technologies that are used for research are not value neutral, but serve to reinforce some values at the expense of others. The authors discuss databases, modelling and simulation, network analysis as examples of technologies which affect the articulation of values. A view of e-social science as a techno-scientific constellation of researchers, technologies and society, in which values are always already embedded, is put forward as a basis for a view of ethics as reflexive and active engagement, conducted with awareness. Methodological pluralism and proactive openness are also proposed as responses to this view of the ethical dimensions of e-social science.