Background Notwithstanding the need to produce evidence-based knowledge on medications for pregnant women, they remain underrepresented in clinical research. Sometimes they are excluded because of their supposed vulnerability, but there are no universally accepted criteria for considering pregnant women as vulnerable. Our aim was to explore whether and if so to what extent pregnant women are vulnerable as research subjects. Method We performed a conceptual and empirical analysis of vulnerability applied to pregnant women. Analysis A conceptual analysis supports Hurst's definition (...) of vulnerability. Consequently, we argue that pregnant women are vulnerable if they encounter an identifiably increased likelihood of incurring additional or greater wrong. According to the literature, this increased likelihood could exist of four alleged features for pregnant women's vulnerability: informed consent, susceptibility to coercion, higher exposure to risk due to lack of knowledge, vulnerability of the fetus. Discussion Testing the features against Hurst's definition demonstrates that they all concern the same issue: pregnant women are only vulnerable because a higher exposure to risk due to lack of scientific knowledge comprises an increased wrong. Research Ethics Committees have a responsibility to protect the vulnerable, but a higher exposure to risk due to lack of scientific knowledge is a much broader issue and also needs to be addressed by other stakeholders. Conclusions The only reason why pregnant women are potentially vulnerable is to the extent that they are increasingly exposed to higher risks due to a lack of scientific knowledge. Accordingly, the discussion can advance to the development of practical strategies to promote fair inclusion of pregnant women in clinical research. (shrink)

There is ambiguity with regard to what counts as an acceptable level of risk in clinical research in pregnant women and there is no input from stakeholders relative to such research risks. The aim of our paper was to explore what stakeholders who are actively involved in the conduct of clinical research in pregnant women deem an acceptable level of risk for pregnant women in clinical research. Accordingly, we used the APOSTEL VI study, a low-risk obstetrical randomised controlled trial, as (...) a case-study. We conducted a prospective qualitative study using 35 in-depth semi-structured interviews and one focus group. We interviewed healthcare professionals, Research Ethics Committee members and regulators who are actively involved in the conduct of clinical research in pregnant women, in addition to pregnant women recruited for the APOSTEL VI case-study in the Netherlands. Three themes characterise the way stakeholders view risks in clinical research in pregnant women in general. Additionally, one theme characterises the way healthcare professionals and pregnant women view risks with respect to the case-study specifically. First, ideas on what constitutes an acceptable level of risk in general ranged from a preference for zero risk for the foetus up to minimal risk. Second, the desirability of clinical research in pregnant women in general was questioned altogether. Third, stakeholders proposed to establish an upper limit of risk in potentially beneficial clinical research in pregnant women in order to protect the foetus and the pregnant woman from harm. Fourth and finally, the case-study illustrates that healthcare professionals’ individual perception of risk may influence recruitment. Healthcare professionals, RECs, regulators and pregnant women are all risk adverse in practice, possibly explaining the continuing underrepresentation of pregnant women in clinical research. Determining the acceptable levels of risk on a universal level alone is insufficient, because the individual perception of risk also influences behaviour towards pregnant women in clinical research. Therefore, bioethicists and researchers might be interested in changing the perception of risk, which could be achieved by education and awareness about the actual benefits and harms of inclusion and exclusion of pregnant women. (shrink)

Editor's suggested further reading in BioEssaysA new paradigm in cell therapy for diabetes: Turning pancreatic α‐cells into β‐cells Abstract.

The rational-agent frame of reference for the analysis of corporate strategic decision-making may be expanded to a moral-agent perspective where decision content is seen as comprising both commercial and ethical factors. Relevant factors may then be classified on the basis of the ethical decision principles to which they relate: rational-egoism, self-referential altruism or deontology. This approach is then applied to the problem of decision support for strategic divestment by MNCs.

Policymakers need to start considering the impact smart connected toys (SCTs) have on children. Equipped with sensors, data processing capacities, and connectivity, SCTs targeting children increasingly penetrate pervasively personal environments. The network of SCTs forms the Internet of Toys (IoToys) and often increases children's engagement and playtime experience. Unfortunately, this young part of the population and, most of the time, their parents are often unaware of SCTs’ far-reaching capacities and limitations. The capabilities and constraints of SCTs create severe side effects (...) at the technical, individual, and societal level. These side effects are often unforeseeable and unexpected. They arise from the technology's use and the interconnected nature of the IoToys, without necessarily involving malevolence from their creators. Although existing regulations and new ethical guidelines for artificial intelligence provide remedies to address some of the side effects, policymakers did not develop these redress mechanisms having children and SCTs in mind. This article provides an analysis of the arising side effects of SCTs and contrasts them with current regulatory redress mechanisms. We thereby highlight misfits and needs for further policymaking efforts. (shrink)

Policymakers need to start considering the impact smart connected toys (SCTs) have on children. Equipped with sensors, data processing capacities, and connectivity, SCTs targeting children increasingly penetrate pervasively personal environments. The network of SCTs forms the Internet of Toys (IoToys) and often increases children's engagement and playtime experience. Unfortunately, this young part of the population and, most of the time, their parents are often unaware of SCTs’ far-reaching capacities and limitations. The capabilities and constraints of SCTs create severe side effects (...) at the technical, individual, and societal level. These side effects are often unforeseeable and unexpected. They arise from the technology's use and the interconnected nature of the IoToys, without necessarily involving malevolence from their creators. Although existing regulations and new ethical guidelines for artificial intelligence provide remedies to address some of the side effects, policymakers did not develop these redress mechanisms having children and SCTs in mind. This article provides an analysis of the arising side effects of SCTs and contrasts them with current regulatory redress mechanisms. We thereby highlight misfits and needs for further policymaking efforts. (shrink)

Qualitative coalitional games (QCGs) were introduced as abstract formal models of goal-oriented cooperative systems. A QCG is a game in which each agent is assumed to have some goal to achieve, and in which agents must typically cooperate with others in order to satisfy their goals. In this paper, we show how it is possible to reason about QCGs using Coalition Logic (CL), a formalism intended to facilitate reasoning about coalitional powers in game-like multiagent systems. We introduce a correspondence relation (...) between QCGs and interpretations for CL, which defines the circumstances under which a CL interpretation correctly characterises a QCG. The complexity of deciding correspondence between QCGs and interpretations for CL is shown to vary from being tractable up to Πp 2-complete, depending on the representation chosen for the QCG and interpretation. We then show how various properties and solution concepts of QCGs can be characterised as CL formula schemes. The ideas are illustrated via a detailed worked example, in which we demonstrate how a model checker can be deployed to investigate whether a particular system has the properties in question. (shrink)

As early as 2002, CIOMS stated that pregnant women should be presumed eligible for participation in research. Despite this position and calls of other well‐recognized organizations, the health needs of pregnant women in research remain grossly under‐researched. Although the presumption of eligibility remains unchanged, the revision of the 2002 CIOMS International ethical guidelines for biomedical research involving human subjects involved a substantive rewrite of the guidance on research with pregnant women and related guidelines, such as those on fair inclusion and (...) vulnerability. However, close reading of the guidelines reveals morally relevant different approaches to fair inclusion of pregnant women and other under‐represented groups, such as children and incompetents. Where CIOMS sets out that children and adolescents must be included unless a good scientific reason justifies their exclusion, no such claim of having to justify exclusion appears in the guideline on pregnant women. Instead, CIOMS claims that research relevant to pregnant women’s health needs must be promoted. This paper analyses how and to what extent the guideline on pregnant women differs from other guidance on fair inclusion in the document. Accordingly, the paper evaluates to what extent the current phrasing may contribute to fair inclusion of pregnant women in research. We will conclude that a system change towards a learning health system is essential to break down the status quo of knowledge generation in the field of medication use during pregnancy and argue that the CIOMS guidelines allow for this system change. (shrink)

L'empirisme transcendantal élaboré par Gilles Deleuze n'est pas le fruit du hasard : il résulte de lectures critiques et d'un véritable remaniement de concepts, notamment dans ses monographies des années cinquante et soixante. Or on lit généralement les œuvres de maturité de Deleuze sans trop s'attarder sur ces premiers écrits. De même, la question de la subjectivité dans son œuvre est souvent laissée au second plan, et l'on constate dans la littérature secondaire des opinions diamétralement opposées quant au statut du (...) sujet chez Deleuze. Le présent ouvrage reconstruit la notion deleuzienne de subjectivité à partir des premières monographies que le philosophe a consacrées à Hume, Kant, Nietzsche et Bergson. Il confronte les œuvres de ces auteurs aux monographies de Deleuze, et réarticule les concepts de la période de 'Différence et répétition' (singularités, habitudes, champ transcendantal, etc.) autour des questions sur la genèse et le statut de la subjectivité."--Page 4 of cover. (shrink)

The aim of this research was to gain insight into the experiences and perspectives of individual members of a Medical Research Ethics Committee regarding their individual roles and possible tensions within and between these roles. We conducted a qualitative interview study among members of a large MREC, supplemented by a focus group meeting. Respondents distinguish five roles: protector, facilitator, educator, advisor and assessor. Central to the role of protector is securing valid informed consent and a proper risk-benefit analysis. The role (...) of facilitator implies that respondents want to think along with and assist researchers in order to help medical science progress. As educators, the respondents want to raise ethical and methodological awareness of researchers. The role of advisor implies that respondents bring in their own expertise. The role of assessor points to contributing to the overall evaluation of the research proposal. Various tensions were identified within and between roles. Within the role of protector, a tension is experienced between paternalism and autonomy. Between the role of protector and facilitator tensions occur when the value of a study is questioned while risks and burdens for the subjects are negligible. Within the role of assessor, a tension is felt between the implicit nature of judgments and the need for more explicit formulations. Awareness of various roles and responsibilities may prevent one-sided views on MREC work, not only by members themselves, but also by researchers. Tensions within and between the roles require reflection by MREC members. (shrink)

Fitch showed that not every true proposition can be known in due time; in other words, that not every proposition is knowable. Moore showed that certain propositions cannot be consistently believed. A more recent dynamic phrasing of Moore-sentences is that not all propositions are known after their announcement, i.e., not every proposition is successful. Fitch's and Moore's results are related, as they equally apply to standard notions of knowledge and belief (S 5 and KD45, respectively). If we interpret ‘successful’ as (...) ‘known after its announcement’ and ‘knowable’ as ‘known after some announcement’, successful implies knowable. Knowable does not imply successful: there is a proposition ϕ that is not known after its announcement but there is another announcement after which ϕ is known. We show that all propositions are knowable in the more general sense that for each proposition, it can become known or its negation can become known. We can get to know whether it is true: ◊(Kϕ ∨ K¬ϕ). This result comes at a price. We cannot get to know whether the proposition was true. This restricts the philosophical relevance of interpreting ‘knowable’ as ‘known after an announcement’. (shrink)

This paper starts from a nonlinear fermion field equation of motion with a strongly coupled self-interaction. Nonperturbative quark solutions of the equation of motion are constructed in terms of a Reggeized infinite component free spinor field. Such a field carries a family of strongly interacting unstable compounds lying on a Regge locus in the analytically continued quark spin. Such a quark field is naturally confined and also possesses the property of asymptotic freedom. Furthermore, the particular field self-regularizes the interactions and (...) naturally breaks the chiral invariance of the equation of motion. We show why and how the existence of such a strongly coupled solution and its particle-family, wave duality forces a change in the field equation of motion such that it conserves C, P, T, although its individual interaction terms are of V-A and thus C, P nonconserving type. (shrink)

Finding meaning in our lives is a central tenet to the human experience and a core contributor to mental health. Individuals tend to actively seek the sources of meaning in their lives or consciously enact efforts to create or “craft” meaning in different life domains. These overall “Life Crafting” behaviors refer to the conscious efforts individuals exert to create meaning in their lives through cognitively framing how they view life, seeking social support systems to manage life challenges, and actively seeking (...) challenges to facilitate personal growth. Specifically, these behaviors are actioned to better align life goals, personal needs, values, and capabilities. However, no psychological assessment instrument currently exists to measure overall life crafting. As such, the purpose of this paper was twofold: to conceptualize life crafting and to develop, validate and evaluate a robust measure of overall life crafting. A mixed-method, multi-study research design was employed. First, nine participants were interviewed to determine the methods or techniques used to craft meaningful life experiences. These methods/techniques were used as indicators to create an initial item pool which was then reviewed by a panel of experts to ensure face validity. Second, in Study 1, the factorial structure of the instrument was explored by gathering data from a convenience sample, with the results showing support for a three-factor structure of life crafting, consisting of cognitive crafting, seeking social support, and seeking challenges. Finally, in Study 2, the aim was to confirm the factorial structure of the Life Crafting scale and to determine its level of internal consistency, partial measurement invariance across genders, and criterion validity [meaning in life, mental health, work engagement, and job burnout ]. The results supported a second-order factorial model of Life Crafting, which comprised of three first-order factors. Therefore, the Life Crafting Scale can be used as a valid and reliable instrument to measure- and track the effectiveness of life crafting interventions. (shrink)

In their 2007 paper, Swierstra and Rip identify characteristic tropes and patterns of moral argumentation in the debate about the ethics of new and emerging science and technologies (or “NEST-ethics”). Taking their NEST-ethics structure as a starting point, we considered the debate about tissue engineering (TE), and argue what aspects we think ought to be a part of a rich and high-quality debate of TE. The debate surrounding TE seems to be predominantly a debate among experts. When considering the NEST-ethics (...) arguments that deal directly with technology, we can generally conclude that consequentialist arguments are by far the most prominently featured in discussions of TE. In addition, many papers discuss principles, rights and duties relevant to aspects of TE, both in a positive and in a critical sense. Justice arguments are only sporadically made, some “good life” arguments are used, others less so (such as the explicit articulation of perceived limits, or the technology as a technological fix for a social problem). Missing topics in the discussion, at least from the perspective of NEST-ethics, are second “level” arguments—those referring to techno-moral change connected to tissue engineering. Currently, the discussion about tissue engineering mostly focuses on its so-called “hard impacts”—quantifiable risks and benefits of the technology. Its “soft impacts”—effects that cannot easily be quantified, such as changes to experience, habits and perceptions, should receive more attention. (shrink)

The precautionary principle is often invoked in relation to pregnant women and may be one of the underlying reasons for their continuous underrepresentation in clinical research. The principle is appealing, because potential fetal harm as a result of research participation is considered to be serious and irreversible. In our paper, we explore through conceptual analysis whether and if so how the precautionary principle should apply to pregnant women. We argue that the principle is a decision-making strategy underlying risk-benefit decisions in (...) clinical research, which can be applied to pregnant women. However, the current application is a strong one, leading to the promotion of absolute exclusion or, less often, absolute inclusion of pregnant women. In order to change this paralyzing situation, a shift toward weak precautionary thinking is necessary. Instead of automatic extreme precaution, a balance will be found between harms and potential benefits of including pregnant women in clinical research. (shrink)

As early as 2002, CIOMS stated that pregnant women should be presumed eligible for participation in research. Despite this position and calls of other well‐recognized organizations, the health needs of pregnant women in research remain grossly under‐researched. Although the presumption of eligibility remains unchanged, the revision of the 2002 CIOMS International ethical guidelines for biomedical research involving human subjects involved a substantive rewrite of the guidance on research with pregnant women and related guidelines, such as those on fair inclusion and (...) vulnerability. However, close reading of the guidelines reveals morally relevant different approaches to fair inclusion of pregnant women and other under‐represented groups, such as children and incompetents. Where CIOMS sets out that children and adolescents must be included unless a good scientific reason justifies their exclusion, no such claim of having to justify exclusion appears in the guideline on pregnant women. Instead, CIOMS claims that research relevant to pregnant women’s health needs must be promoted. This paper analyses how and to what extent the guideline on pregnant women differs from other guidance on fair inclusion in the document. Accordingly, the paper evaluates to what extent the current phrasing may contribute to fair inclusion of pregnant women in research. We will conclude that a system change towards a learning health system is essential to break down the status quo of knowledge generation in the field of medication use during pregnancy and argue that the CIOMS guidelines allow for this system change. (shrink)

The paper is concerned with the psychological relevance of a logical model for deductive reasoning. We propose a new way to analyze logical reasoning in a deductive version of the Mastermind game implemented within a popular Dutch online educational learning system (Math Garden). Our main goal is to derive predictions about the difficulty of Deductive Mastermind tasks. By means of a logical analysis we derive the number of steps needed for solving these tasks (a proxy for working memory load). Our (...) model is based on the analytic tableaux method, known from proof theory. We associate the difficulty of Deductive Mastermind game-items with the size of the corresponding logical trees obtained by the tableaux method. We derive empirical hypotheses from this model. A large group of students (over 37 thousand children, 5–12 years of age) played the Deductive Mastermind game, which gave empirical difficulty ratings of all 321 game-items. The results show that our logical approach predicts these item ratings well, which supports the psychological relevance of our model. (shrink)

The participation of vulnerable patients in clinical research poses apparent ethical dilemmas. Depending on the nature of the vulnerability, their participation may challenge the ethical principles of autonomy, non-maleficence, or justice. On the other hand, non-participation may preclude the building of a knowledge base that is a prerequisite for defining the optimal clinical management of vulnerable patients. Such clinical uncertainty may also incur substantial economic costs. We present the participation of pre-menopausal women with atrial fibrillation in trials of novel oral (...) anticoagulant drugs as a case study. Due to their non-participation in pivotal trials, it is uncertain whether for them, the risks that are associated with these drugs are outweighed by the advantages compared with conventional treatment. We addressed the question whether research of this new class of drugs in this subgroup would be appropriate from both, an ethical as well an economic perspective. We used the method of specifying norms as a wider framework to resolve the apparent ethical dilemma, while incorporating the question whether research of oral anticoagulants in premenopausal women with atrial fibrillation can be justified on economic grounds. For the latter, the results of a value-of-information analysis were used. Further clinical research on NOACs in premenopausal women with atrial fibrillation can be justified on both, ethical and economic grounds. Addressing apparent ethical dilemmas by invoking a method such as specifying norms can improve the quality of public practical reasoning. As such, the method should also prove valuable to committees that have formally been granted the authority to review trial protocols and proposals for scientific research. (shrink)

In the early eighteenth century Newtonianism became popular in the Netherlands both in academic and non-academic circles. The ‘Book of Nature’ was interpreted with the help of Newton’s natural philosophy and his ideas about a providential deity, thereby greatly enhancing the attractiveness of physico-theology in the eighteenth-century United Provinces. Like other Europeans the Dutch welcomed physico-theology as a strategic means in their battle against irreligion and atheism. Bernard Nieuwentijt, Johan Lulofs, Petrus Camper, and Johannes Florentius Martinet were prominent experts in (...) the field. Combining Newtonian notions with Leibnizian optimism and romanticist trends, physico-theology remained popular in the Netherlands well into the nineteenth century.Author Keywords: Apologetics; Dutch Enlightenment; Physico-theology; Prophetic theology; Argument from design; Empiricism. (shrink)