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)

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)

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)

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)

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)

BackgroundWith advances in sequencing technologies, increasing numbers of people are being informed about a genetic disease identified in their family. In current practice, probands are asked to inform at-risk relatives about the diagnosis. However, previous research has shown that relatives are sometimes not informed due to barriers such as family conflicts. Research on family communication in genetic diseases aims to explore the difficulties encountered in informing relatives and to identify ways to support probands in this.Main bodyResearch on family communication may (...) also reveal that participants did not inform their relatives about the risk of a serious genetic condition, even when preventive and treatment options are available. Researchers may then face a dilemma: Do they need to warn at-risk relatives about the finding? Or do they keep silent due to prior confidentiality agreements with study participants?ConclusionsWe believe that the absolute confidence promised to research participants outweighs the interests of their relatives, even though it can be claimed that relatives at risk of a genetic disease do, in principle, have a right to know information collected about their health. Not respecting confidentiality agreements could cause distrust between researchers and research participants and possibly harm the relationship between probands and relatives. Relatives' health interests can still be taken into account without jeopardizing participant trust, by considering alternative scenarios, including sharing general study findings on the barriers participants experience with their healthcare professionals and by offering participants psychosocial support for family communication. (shrink)