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)

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)

BackgroundThere 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.MethodsWe 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.ResultsThree 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.ConclusionsHealthcare 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)

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)

Supercommentary, with commentaries on Praśastapādabhāṣya, a work on Kaṇāda's Vaiśeṣikasūtra, treatise on the Vaiśeṣika school in Hindu philosophy.

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)

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)

Deontic Logic goes back to Ernst Mally’s 1926 work, Grundgesetze des Sollens: Elemente der Logik des Willens [Mally. E.: 1926, Grundgesetze des Sollens: Elemente der Logik des Willens, Leuschner & Lubensky, Graz], where he presented axioms for the notion ‘p ought to be the case’. Some difficulties were found in Mally’s axioms, and the field has much developed. Logic of Knowledge goes back to Hintikka’s work Knowledge and Belief [Hintikka, J.: 1962, Knowledge and Belief: An Introduction to the Logic of (...) the Two Notions, Cornell University Press] in which he proposed formal logics of knowledge and belief. This field has also developed quite a great deal and is now the subject of the TARK conferences. However, there has been relatively little work combining the two notions of knowledge (belief) with the notion of obligation. (See, however, [Lomuscio, A. and Sergot, M.: 2003, Studia Logica 75 63–92; Moore, R. C.: 1990, In J. F. Allen, J. Hendler and A. Tate (eds.), Readings in Planning, Morgan Kaufmann Publishers, San Mateo, CA]) In this paper we point out that an agent’s obligations are often dependent on what the agent knows, and indeed one cannot reasonably be expected to respond to a problem if one is not aware of its existence. For instance, a doctor cannot be expected to treat a patient unless she is aware of the fact that he is sick, and this creates a secondary obligation on the patient or someone else to inform the doctor of his situation. In other words, many obligations are situation dependent, and only apply in the presence of the relevant information. Thus a case for combining Deontic Logic with the Logic of Knowledge is clear. We introduce the notion of knowledge based obligation and offer an S5, history based Kripke semantics to express this notion, as this semantics enables us to represent how information is transmitted among agents and how knowledge changes over time as a result of communications. We consider both the case of an absolute obligation (although dependent on information) as well as the (defeasible) notion of an obligation which may be over-ridden by more relevant information. For instance a physician who is about to inject a patient with drug d may find out that the patient is allergic to d and that she should use d′ instead. Dealing with the second kind of case requires a resort to non-monotonic reasoning and the notion of justified belief which is stronger than plain belief, but weaker than absolute knowledge in that it can be over-ridden. This notion of justified belief also creates a derived notion of default obligation where an agent has, as far as the agent knows, an obligation to do some action a. A dramatic application of this notion is our analysis of the Kitty Genovese case where, in 1964, a young woman was stabbed to death while 38 neighbours watched from their windows but did nothing. The reason was not indifference, but none of the neighbours had even a default obligation to act, even though, as a group, they did have an obligation to take some action to protect Kitty. (shrink)

We show that the spectrum of a sentence ϕ in Counting Monadic Second Order Logic (CMSOL) using one binary relation symbol and finitely many unary relation symbols, is ultimately periodic, provided all the models of ϕ are of clique width at most k, for some fixed k. We prove a similar statement for arbitrary finite relational vocabularies τ and a variant of clique width for τ-structures. This includes the cases where the models of ϕ are of tree width at most (...) k. For the case of bounded tree-width, the ultimate periodicity is even proved for Guarded Second Order Logic GSOL. We also generalize this result to many-sorted spectra, which can be viewed as an analogue of Parikh's Theorem on context-free languages, and its analogues for context-free graph grammars due to Habel and Courcelle. Our work was inspired by Gurevich and Shelah (2003), who showed ultimate periodicity of the spectrum for sentences of Monadic Second Order Logic where only finitely many unary predicates and one unary function are allowed. This restriction implies that the models are all of tree width at most 2, and hence it follows from our result. (shrink)

Engineering is a practice that must function in an environment of incomplete and uncertain knowledge. This environment has become even more difficult in an increasingly complex world. Engineering ethics has to be framed and taught in a way that addresses these realities. This paper proposes a combination of the philosophy of pragmatism and the ethic of care as a possible framework for the practice of engineering ethics that can provide flexibility and openness to address engineering ethics problems more realistically within (...) the ethos and culture of engineering. Embedding values into practice, pragmatism and care provide a broad, reflective, and corrective framework for engineering ethics that can accommodate the realities in which engineering operates. It is shown that these two approaches are more consonant with design methodologies and have a natural fit with design thinking, so they mesh well with what engineers do and with the complexities of their work today. As humans more and more try to alter the socio-techno-natural world, e.g., the earth’s climate, the combination of pragmatism and care will allow enhanced ethical behavior. Alterations to complex adaptive systems will produce highly uncertain results that require engineers to have a mindset that allows them to act with humility in the face of significant uncertainty and potential catastrophic failures. (shrink)

ABSTRACT Peter Hägel's Billionaires in World Politics undoubtedly fills a gap in the literature of international relations and global governance. My comment seeks to highlight that Hägel's (2020. Billionaires in World Politics. 1st ed. Oxford Scholarship Online. Oxford: Oxford University Press) work allows us to advance our understanding of how these private actors can be understood as legitimate authorities and how they can contribute to the legitimacy of the international order. I divide my commentary into three points: the first concerns (...) the approach to billionaires from their individual agency (the individual approach), the second relates to the separation between the state and the global levels (the division approach), and the third presents questions on political legitimacy that arise from his case studies (the legitimacy question). (shrink)

Universities introduce intermediate assessment because it is understood to have positive effects on student behaviour and achievement. Yet, how intermediate assessment is perceived might be conditional for its success. The current study investigates both teachers’ and students’ perceptions of intermediate assessment. Teachers and students were interviewed and Student Evaluations of Teaching were examined. Results indicate that both teachers and students had generally positive perceptions of intermediate assessment. However, the two groups provided different reasons for their positive perceptions. Teachers and students (...) agreed that intermediate assessment helps students to keep up with their study work. Moreover, teachers mentioned that they could assess various knowledge and skills with intermediate assessment, whereas students preferred intermediate assessments to test the same knowledge and skills as the final exam. This finding suggests that teachers and students in our study had different goals... (shrink)

We propose a new relevance sensitive model for representing and revising belief structures, which relies on a notion of partial language splitting and tolerates some amount of inconsistency while retaining classical logic. The model preserves an agent's ability to answer queries in a coherent way using Belnap's four-valued logic. Axioms analogous to the AGM axioms hold for this new model. The distinction between implicit and explicit beliefs is represented and psychologically plausible, computationally tractable procedures for query answering and belief..

One interpretation of the conditional If P then Q is as saying that the probability of Q given P is high. This is an interpretation suggested by Adams (1966) and pursued more recently by Edgington (1995). Of course, this probabilistic conditional is nonmonotonic, that is, if the probability of Q given P is high, and R implies P, it need not follow that the probability of Q given R is high. If we were confident of concluding Q from the fact (...) that we knew P, and we have stronger information R, we can no longer be confident of Q. We show nonetheless that usually we would still be justified in concluding Q from R. In other words, probabilistic conditionals are mostly monotonic. (shrink)

Journal of Philosophical Logic 34, 97-119, 2005.

Subset Spaces were introduced by L. Moss and R. Parikh in [8]. These spaces model the reasoning about knowledge of changing states.In [2] a kind of subset space called intersection space was considered and the question about the existence of a set of axioms that is complete for the logic of intersection spaces was addressed. In [9] the first author introduced the class of directed spaces and proved that any set of axioms for directed frames also characterizes intersection spaces.We (...) give here a complete axiomatization for directed spaces. We also show that it is not possible to reduce this set of axioms to a finite set. (shrink)

ABSTRACTEngland and Australia have abandoned self-regulation of the legal profession, yet Canadian law societies continue to function on this basis. This article argues that the self-regulatory mod...

We investigate the semantics of messages, and argue that the meaning ofa message is naturally and usefully given in terms of how it affects theknowledge of the agents involved in the communication. We note thatthis semantics depends on the protocol used by the agents, and thus not only the message itself, but also the protocol appears as a parameter in the meaning. Understanding this dependence allows us to give formal explanations of a wide variety of notions including language dependence, implicature, (...) and the amount of information in a message. (shrink)

The standard theory for belief revision provides an elegant and powerful framework for reasoning about how a rational agent should change its beliefs when confronted with new information. However, the agents considered are extremely idealized. Some recent models attempt to tackle the problem of plausible belief revision by adding structure to the belief bases and using nonstandard inference operations. One of the key ideas is that not all of an agent's beliefs are relevant for an operation of belief change.In this (...) paper we incorporate the insights pertaining to local change and relevance sensitivity with the use of approximate inference relations. These approximate inference relations offer us partial solutions at any stage of the revision process. The quality of the approximations improves as we allow for more and more resources to be used. We are provided with upper and lower bounds to what would be obtained with the use of classical inference. (shrink)

In Language and Equilibrium, Prashant Parikh offers a new account of meaning for natural language. He argues that equilibrium, or balance among multiple interacting forces, is a key attribute of language and meaning and shows how to derive the meaning of an utterance from first principles by modeling it as a system of interdependent games.His account results in a novel view of semantics and pragmatics and describes how both may be integrated with syntax. It considers many aspects of meaning--including (...) literal meaning and implicature--and advances a detailed theory of definite descriptions as an application of the framework.Language and Equilibrium is intended for a wide readership in the cognitive sciences, including philosophers, linguists, and artificial intelligence researchers as well as neuroscientists, psychologists, and economists interested in language and communication. (shrink)

Recent studies indicate that mammalian chromosomes contain discretecis‐acting loci that control replication timing, mitotic condensation, and stability of entire chromosomes. Disruption of the large non‐coding RNA gene ASAR6 results in late replication, an under‐condensed appearance during mitosis, and structural instability of human chromosome 6. Similarly, disruption of the mouse Xist gene in adult somatic cells results in a late replication and instability phenotype on the X chromosome. ASAR6 shares many characteristics with Xist, including random mono‐allelic expression and asynchronous replication timing. (...) Additional “chromosome engineering” studies indicate that certain chromosome rearrangements affecting many different chromosomes display this abnormal replication and instability phenotype. These observations suggest that all mammalian chromosomes contain “inactivation/stability centers” that control proper replication, condensation, and stability of individual chromosomes. Therefore, mammalian chromosomes contain four types ofcis‐acting elements, origins, telomeres, centromeres, and “inactivation/stability centers”, all functioning to ensure proper replication, condensation, segregation, and stability of individual chromosomes. (shrink)