How can new drug lead suggestions beinferred from neurophysiological models? This paperaddresses this question based on a case study ofresearch into Parkinson''s disease at the GroningenUniversity Department of Pharmacy. It is argued thatneurophysiological box-and-arrow models can beunderstood as qualitative differential equationmodels. An inference task is defined to helpunderstand and possibly aid the discovery andexplanation of new drug lead suggestions.

This paper explores structuralism as a way to model theories from scientific practice. As a case study I analyzed a theory about the dynamics of the basal ganglia, a part of the brain that is involved in Parkinson's disease. After introducing the case study I explore how to structurally represent qualitative assumptions about disease, intervention and dynamical systems in general. I further explicate the structure of the basal ganglia theory in detail, how it explains Parkinson's disease and how it implies (...) treatments. I close with a consideration of how a structuralist representation could be useful in practice to explore and develop theories with the aid of a computer. (shrink)

We report on the small-scale (0.5 13 h - 1M, a large-scale bias of ~2.0 and a satellite fraction of 12 ± 2 per cent. Thus, these galaxies occupy haloes with average masses in between those of the higher redshift BOSS CMASS sample and the original SDSS I/II luminous red galaxy sample © 2012 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society © doi:10.1093/mnras/sts314.

BackgroundObtaining informed consent for intravenous thrombolysis in acute ischemic stroke can be challenging, and little is known about if and how the informed consent procedure is performed by neurologists in clinical practice. This study examines the procedure of informed consent for intravenous thrombolysis in acute ischemic stroke in high-volume stroke centers in the Netherlands.MethodsIn four high volume stroke centers, neurology residents and attending neurologists received an online questionnaire concerning informed consent for thrombolysis with tissue-type plasminogen activator (tPA). The respondents were (...) asked to report their usual informed consent practice for tPA treatment and their considerations on whether informed consent should be obtained.ResultsFrom the 203 invited clinicians, 50% (n = 101) completed the questionnaire. One-third of the neurology residents (n = 21) and 21% of the neurologists (n = 8) reported that they always obtain informed consent for tPA treatment. If a patient is not capable of providing informed consent, 30% of the residents (n = 19) reported that they start tPA treatment without informed consent. In these circumstances, 53% of the neurologists (n = 20) reported that the resident under their supervision would start tPA treatment without informed consent. Most neurologists (n = 21; 55%) and neurology residents (n = 45; 72%) obtained informed consent within one minute. None of the respondents used more than five minutes for informed consent. Important themes regarding obtaining informed consent for treatment were patients’ capacity, and medical, ethical and legal considerations.ConclusionThe current practice of informed consent for thrombolysis in acute ischemic stroke varies among neurologists and neurology residents. If informed consent is obtained, most clinicians stated to obtain informed consent within one minute. In the future, a shortened information provision process may be applied, making a shift from informed consent to informed refusal, while still considering the patient’s capacity, stroke severity, and possible treatment delays. (shrink)

Chervenak and McCullough, authors of the most acknowledged ethical framework for maternal–fetal surgery, rely on the ‘ethical–obstetrical’ concept of the fetus as a patient in order to determine what is morally owed to fetuses by both physicians and the women who gestate them in the context of prenatal surgery. In this article, we reconstruct the argumentative structure of their framework and present an internal criticism. First, we analyse the justificatory arguments put forward by the authors regarding the moral status of (...) the fetus qua patient. Second, we discuss the internal coherence and consistency of the moral obligations those authors derive from that concept. We claim that some of the dilemmas their approach is purported to avoid, such as the debate about the independent moral status of the fetus, and the foundation of the moral obligations of pregnant women (towards the fetuses they gestate) are not, all things considered, avoided. Chervenak and McCullough construct the obligations of physicians as obligations towards entities with equal moral status. But, at the same time, they assume that the woman has an independent moral status while the moral status of the fetus is dependent on the decision of the woman to present it to a physician for care. According to the logic of their own argumentation, Chervenak and McCullough implicitly admit a different moral status of the woman and the fetus, which will lead to different ascription of duties of the physician than those they ascribed. (shrink)

This article focuses on maternal-fetal surgery (MFS) and on the concept of clinical equipoise that is a widely accepted requirement for conducting randomized controlled trials (RCT). There are at least three reasons why equipoise is unsuitable for MFS. First, the concept is based on a misconception about the nature of clinical research and the status of research subjects. Second, given that it is not clear who the research subject/s in MFS is/are, if clinical equipoise is to be used as a (...) criterion to test the ethical appropriateness of RCT, its meaning should be unambiguous. Third, because of the multidisciplinary character of MFS, it is not clear who should be in equipoise. As a result, we lack an adequate criterion for the ethical review of MFS protocols. In our account, which is based on Chervenak and McCullough's seminal work in the field of obstetric ethics, equipoise is abandoned. and RCT involving MFS can be ethically initiated when a multidisciplinary ethics review board (ERB), having an evidence-based assessment of the risks involved, is convinced that the value of answering the research hypothesis, for the sake of the health interests of future pregnant women carrying fetuses with certain congenital birth defects, justifies the actual risks research participants might suffer within a set limit of low/manageable. (shrink)

Patient-reported outcomes are frequently used for medical decision making, at the levels of both individual patient care and healthcare policy. Evidence increasingly shows that PROs may be influenced by patients’ response shifts and dispositions. We identify how response shifts and dispositions may influence medical decisions on both the levels of individual patient care and health policy. We provide examples of these influences and analyse the consequences from the perspectives of ethical principles and theories of just distribution. If influences of response (...) shift and disposition on PROs and consequently medical decision making are not considered, patients may not receive optimal treatment and health insurance packages may include treatments that are not the most effective or cost-effective. We call on healthcare practitioners, researchers, policy makers, health insurers, and other stakeholders to critically reflect on why and how such patient reports are used. (shrink)

This study examines the central contention of instrumental stakeholder theory— namely, that firms that breed trust-based, cooperative ties with their stakeholders will have a competitive advantage over firms that do not. Acase study of the introduction ofgenetically modified food products in the Netherlands provided the basis for the empirical analysis. The results support the instrumental stakeholder management thesis, showing that stakeholder integration, through the development ofmutually enforcing relationships with external parties, may result in both organizational learning and societal legitimacy.

Within current debates about the future impact of Artificial Intelligence on human society, roughly three different perspectives can be recognised: the technology-centric perspective, claiming that AI will soon outperform humankind in all areas, and that the primary threat for humankind is superintelligence; the human-centric perspective, claiming that humans will always remain superior to AI when it comes to social and societal aspects, and that the main threat of AI is that humankind’s social nature is overlooked in technological designs; and the (...) collective intelligence-centric perspective, claiming that true intelligence lies in the collective of intelligent agents, both human and artificial, and that the main threat for humankind is that technological designs create problems at the collective, systemic level that are hard to oversee and control. The current paper offers the following contributions: a clear description for each of the three perspectives, along with their history and background; an analysis and interpretation of current applications of AI in human society according to each of the three perspectives, thereby disentangling miscommunication in the debate concerning threats of AI; and a new integrated and comprehensive research design framework that addresses all aspects of the above three perspectives, and includes principles that support developers to reflect and anticipate upon potential effects of AI in society. (shrink)

Our ability to select relevant information from the environment is limited by the resolution of attention – i.e., the minimum size of the region that can be selected. Neural mechanisms that underlie this limit and its development are not yet understood. Functional MRI was performed during an object tracking task in 7- and 11-year-old children, and in young adults. Object tracking activated canonical fronto-parietal attention systems and motion-sensitive area MT in children as young as 7 years. Object tracking performance improved (...) with age, together with stronger recruitment of parietal attention areas and a shift from low-level to higher-level visual areas. Increasing the required resolution of spatial attention – which was implemented by varying the distance between target and distractors in the object tracking task – led to activation increases in fronto-insular cortex, medial frontal cortex including anterior cingulate cortex (ACC) and supplementary motor area, superior colliculi, and thalamus. This core circuitry for attentional precision was recruited by all age groups, but ACC showed an age-related activation reduction. Our results suggest that age-related improvements in selective visual attention and in the resolution of attention are characterized by an increased use of more functionally specialized brain regions during the course of development. (shrink)

This paper explores structuralism as a way to model theories from scientific practice. As a case study I analyzed a theory about the dynamics of the basal ganglia, a part of the brain that is involved in Parkinson's disease. After introducing the case study I explore how to structurally represent qualitative assumptions about disease, intervention and dynamical systems in general. I further explicate the structure of the basal ganglia theory in detail, how it explains Parkinson's disease and how it implies (...) treatments. I close with a consideration of how a structuralist representation could be useful in practice to explore and develop theories with the aid of a computer. (shrink)

Van den Berg, I.P., Extended use of IST, Annals of Pure and Applied Logic 58 73–92. Internal Set Theory is an axiomatic approach to nonstandard analysis, consisting of three axiom schemes, Transfer , Idealization , and Standardization . We show that the range of application of these axiom schemes may be enlarged with respect to the original formulation. Not only more kinds of formulas are allowed, but also different settings. Many examples illustrate these extensions. Most concern formal aspects of nonstandard (...) asymptotics. (shrink)

Recent publications on digital health technologies highlight the importance of ‘responsible’ use. References to the concept of responsibility are, however, frequently made without providing clear definitions of responsibility, thus leaving room for ambiguities. Addressing these uncertainties is critical since they might lead to misunderstandings, impacting the quality and safety of healthcare delivery. Therefore, this study investigates how responsibility is interpreted in the context of using digital health technologies, including artificial intelligence (AI), telemonitoring, wearables and mobile apps. We conducted a scoping (...) review with a systematic search in PubMed, Web of Science, Embase, CINAHL and Philosopher’s Index. A total of 34 articles were included and categorized using a theoretical framework of responsibility aspects, and revealed two main findings. First, we found that digital health technologies can expand and shift existing ‘role responsibilities’ among caregivers, patients and technology. Second, moral responsibility is often equated with liability or accountability, without clear justification. Articles describe new ways in which physicians can be held accountable, particularly in the context of AI, and discuss the emergence of a ‘responsibility gap’ where no-one can be fully responsible for AI-generated outcomes. The literature also shows that m-Health technologies can increase patients’ accountability for their own health. However, there was limited discussion in the reviewed literature on whether these attributions of accountability are appropriate. We conclude with implications for practice and suggestions for expanding the theoretical framework of moral responsibility, recommending further study on responsibility of collectives and artificial entities, and on the role of virtue in digital health. (shrink)

Much clinical and ethnographic evidence suggests that humans, like many other organisms, are selected to avoid close inbreeding because of the fitness costs of inbreeding depression. The proximate mechanism of human inbreeding avoidance seems to be precultural, and to involve the interaction of genetic predispositions and environmental conditions. As first suggested by E. Westermarck, and supported by evidence from Israeli kibbutzim, Chinese sim-pua marriage, and much convergent ethnographic and clinical evidence, humans negatively imprint on intimate associates during a critical period (...) of early childhood.There is also much evidence that, like other social animals, humans do not seek to maximize outbreeding, but rather to maintain an optimal balance between outbreeding and inbreeding.Closeinbreeding reduces fitness through inbreeding depression, butsomeinbreeding brings the benefits of nepotism. For simple, stateless, horticultural societies, the optimal balance seems to be achieved by a combination of precultural inbreeding avoidance of relatives with anr≤·25 and cultural rules of preferential marriage with kin withr≥·25. Adjustment of the coefficient of inbreeding to other ecological settings seems to be largely cultural. An interactive model of “culture in nature” is presented, in which culture is seen as coevolving with genes to produce the maxiniization of individual inclusive fitness. (shrink)

Meta-theories, base-theories and theories of practice in Pratical Theology The problem of meta-theories and base-theories, their interaction and the influence of each on the scientific process, have widely been debated in practical theology. In South Africa two meta-theories namely the system- theory together with the theory that social science is busy with the study of actions, are having the greater deal of attention. The purpose of this article is to point out the fact that an early and absolute choice of (...) particular meta-theories, restricts the work of practical theology because it will influence your base-theories, and can weaken the theological content of practical theology. An attempt is made to offer a model by which the interaction between, meta-theories, base-theories and theories of practice can he understood and which can also help the theologian, busy with practical theology, to steer clear of problems and understand the meta- influences in his own scientific work. (shrink)

The article gives a review of inedited sources dealing with the Belgian contribution to European integration in the years 1945-1955. Such sources are kept in the Algemeen Rijksarchief, in the Parliament, various ministerial departments, the Navorsings- en Studiecentrum voor de Geschiedenis van de Tweede Wereldoorlog, study centres of the major political parties, a number of non-governmental organizations as well as the private archives of a number of politicians.

The nonstandard stroboscopy method links discrete-time ordinary difference equations of first-order and continuous-time, ordinary differential equations of first order. We extend this method to the second order, and also to an elementary, yet general class of partial difference/differential equations, both of first and second order. We thus obtain straightforward discretizations and continuizations, even avoiding change of variables. In fact, we create intermediary objects: partial difference equations with S-continuous solutions, which have both discrete and continuous properties.