This paper presents Cusanus’ dialogue of 1462, named after and centred on the concept of non-aliud, and exploits its speculative resources for conceiving the relationship between God and the realm of finite entities. Furthermore, it points to the elements of self-constitution of the absolute and of the latter’s grounding relation towards the contingent. Finally, it is argued that Cusanus’ concept of non-aliud offers a valuable contribution to the present debate about an adequate concept of God.

Founded or unfounded, these objections have not as yet received an adequate answer, i.e., an explanation of the possibility of a philosophy of subjectivity as constituting a reasonable addition to the philosophia perennis, a certain broadening of its perspective, without amounting instead to a simple jettisoning of the thought and gains of centuries. The writings of a Marcel, for example, do not provide such an explanation. Composed wholly within the perspective that is in question, and a little too cavalier in (...) their dismissal of scholastic thought, they cannot really come to grips with that thought, or thereby allay its reasonable suspicions. Even the work of P. de Finance is not wholly satisfactory on this point. As a reviewer of his latest book points out, P. de Finance makes constant and brilliant use of insights gained from the perspective of subjectivity, but he skirts around, without ever really meeting head on, the problems it raises. (shrink)

The difficulty with this point of view and the reason why I characterize it as false do not spring from the mere fact that thought is abstract while experience is concrete. For, on the one hand, the abstract character of thought need not be interpreted negatively, as leaving out the rich variety and profusion of the concrete world in favor of some bare common denominator. Concreteness itself can be seen as a limitation which thought overcomes.ion then becomes an enriching process, (...) a process by which the mind, out of its own superior abundance, illumines and completes the data presented to it, so that from the welter and confusion of particular instances it is able to grasp the universal and valid-for-all, and from the fugitive contingency of the concrete to redeem the abidingly true. In this light, abstractiveness is not a vice but a virtue of thought and, far from weakening the intellectualist position, serves rather to reinforce it. (shrink)

The elaboration of a complete and original system of philosophy in any age demands an intellect of great scope and power. In an age like our own, which has become increasingly hostile to systematic thought, it demands a good deal of courage as well. The Modes of Being of Mr. Weiss proves that he possesses both to a high degree.

BackgroundTo probe the functional role of brain oscillations, transcranial alternating current stimulation has proven to be a useful neuroscientific tool. Because of the excessive tACS-caused artifact at the stimulation frequency in electroencephalography signals, tACS + EEG studies have been mostly limited to compare brain activity between recordings before and after concurrent tACS. Critically, attempts to suppress the artifact in the data cannot assure that the entire artifact is removed while brain activity is preserved. The current study aims to evaluate the (...) feasibility of specific artifact correction techniques to clean tACS-contaminated EEG data.New MethodIn the first experiment, we used a phantom head to have full control over the signal to be analyzed. Driving pre-recorded human brain-oscillation signals through a dipolar current source within the phantom, we simultaneously applied tACS and compared the performance of different artifact-correction techniques: sine subtraction, template subtraction, and signal-space projection. In the second experiment, we combined tACS and EEG on one human subject to demonstrate the best-performing data-correction approach in a proof of principle.ResultsThe tACS artifact was highly attenuated by SSP in the phantom and the human EEG; thus, we were able to recover the amplitude and phase of the oscillatory activity. In the human experiment, event-related desynchronization could be restored after correcting the artifact.Comparison With Existing MethodsThe best results were achieved with SSP, which outperformed sine subtraction and template subtraction.ConclusionOur results demonstrate the feasibility of SSP by applying it to a phantom measurement with pre-recorded signal and one human tACS + EEG dataset. For a full validation of SSP, more data are needed. (shrink)

The inquiry analyses how Fichte rejects the reproach of founding the Wissenschaftslehre from the perspective of the individual I-subject in his lectures about the facts of consciousness, held in Berlin between 1810 and 1813. Instead it becomes clear that according to Fichte, the crucial instance of “I” has to be considered as transindividual. Its individualisation matters only as far as causal effects on material bound reality are concerned, while the individuals join again the absolute life’s unity by speculative thought and (...) moral acting.Der Beitrag untersucht, wie Fichte in seinen Berliner Vorlesungen über die Tatsachen des Bewusstseins der Jahre 1810 bis 1813 den Vorwurf zurückweist, von einem individuellen Ich-Subjekt aus die Wissenschaftslehre zu begründen. Statt dessen wird deutlich, dass die entscheidende Ich-Instanz Fichte zufolge überindividuell verstanden werden muss. Ihre Individualisierung ist nur mit Blick auf das kausale Wirken in der materiellen Wirklichkeit von Bedeutung, während die Individuen im spekulativen Denken und im sittlichen Handeln wieder zur Einheit des absoluten Lebens zurückfinden. (shrink)

The Dutch law states that a physician may perform euthanasia according to a written advance euthanasia directive when a patient is incompetent as long as all legal criteria of due care are met. This may also hold for patients with advanced dementia. We investigated the differing opinions of physicians and members of the general public on the acceptability of euthanasia in patients with advanced dementia.

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)

Most of these eight essays on contemporary figures were given as lectures or speeches between 1990 and 1996. A piece on Ernst Cassirer’s humanistic legacy gives the collection its title, but the other subjects treated are far-ranging: Karl Jaspers on the clash of religious cultures, Georg Henrik von Wright’s noncognitive ethics, Gershom Scholem’s magisterial biography of the kabbalist Sabbatai Sevi, Karl-Otto Apel’s hermeneutics, Johann Baptist Metz on the Jewish element in Christianity, Michael Theunissen on the relation of negative theology to (...) social theory, and a review of the work of script writer and film director Alexander Kluge. Habermas unifies this panoply by his fascination with the transformation of the modern West’s key symbols through their confrontation with other cultures. Prime among these symbols are language and religious doctrines, especially Christian and Jewish. When he examines this general theme in particular cases, Habermas first presents an exposé of a thinker, then raises critical questions, and finally points out insights of enduring significance. One decided advantage of his method is its attention to clarity and organization. Probably because these essays were originally delivered orally, they never leave the reader in doubt as to what topics they will handle and when each is being taken up. (shrink)

In paediatric oncology, research and treatments are often closely combined, which may compromise voluntary informed consent of parents. We identified two key scenarios in which voluntary informed consent for paediatric oncology studies is potentially compromised due to the intertwinement of research and care. The first scenario is inclusion by the treating paediatric oncologist, the second scenario concerns treatments confined to the research context. In this article we examine whether voluntary informed consent of parents for research is compromised in these two (...) scenarios, and if so whether this is also morally problematic. For this, we employ the account of voluntary consent from Nelson and colleagues, who assert that voluntary consent requires substantial freedom from controlling influences. We argue that, in the absence of persuasion or manipulation, inclusion by the treating physician does not compromise voluntariness. However, it may function as a risk factor for controlling influence as it narrows the scope within which parents make decisions. Furthermore, physician appeal to reciprocity is not controlling as it constitutes persuasion. In addition, framing information is a form of informational manipulation and constitutes a controlling influence. In the second scenario, treatments confined to the research context qualify as controlling if the available options are restricted through manipulation of options. Although none of the influences is morally problematic in itself, a combination of influences may create morally problematic instances of involuntary informed consent. Therefore, safeguards should be implemented to establish an optimal environment for parents to provide voluntary informed consent in an integrated research-care context. (shrink)

This is, to the best of my knowledge, the first published attempt at a rigorous logical formalization of a passage in Leibniz's Monadology. The method we followed was suggested by Johannes Czermak.

In paediatric oncology, research and treatments are often closely combined, which may compromise voluntary informed consent of parents. We identified two key scenarios in which voluntary informed consent for paediatric oncology studies is potentially compromised due to the intertwinement of research and care. The first scenario is inclusion by the treating paediatric oncologist, the second scenario concerns treatments confined to the research context. In this article we examine whether voluntary informed consent of parents for research is compromised in these two (...) scenarios, and if so whether this is also morally problematic. For this, we employ the account of voluntary consent from Nelson and colleagues, who assert that voluntary consent requires substantial freedom from controlling influences. We argue that, in the absence of persuasion or manipulation, inclusion by the treating physician does not compromise voluntariness. However, it may function as a risk factor for controlling influence as it narrows the scope within which parents make decisions. Furthermore, physician appeal to reciprocity is not controlling as it constitutes persuasion. In addition, framing information is a form of informational manipulation and constitutes a controlling influence. In the second scenario, treatments confined to the research context qualify as controlling if the available options are restricted through manipulation of options. Although none of the influences is morally problematic in itself, a combination of influences may create morally problematic instances of involuntary informed consent. Therefore, safeguards should be implemented to establish an optimal environment for parents to provide voluntary informed consent in an integrated research-care context. (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)

The rapid expansion of research on Brain-Computer Interfaces is not only due to the promising solutions offered for persons with physical impairments. There is also a heightened need for understanding BCIs due to the challenges regarding ethics presented by new technology, especially in its impact on the relationship between man and machine. Here we endeavor to present a scoping review of current studies in the field to gain insight into the complexity of BCI use. By examining studies related to BCIs (...) that employ social research methods, we seek to demonstrate the multitude of approaches and concerns from various angles in considering the social and human impact of BCI technology. For this scoping review of research on BCIs’ social and ethical implications, we systematically analyzed six databases, encompassing the fields of medicine, psychology, and the social sciences, in order to identify empirical studies on BCIs. The search yielded 73 publications that employ quantitative, qualitative, or mixed methods. Of the 73 publications, 71 studies address the user perspective. Some studies extend to consideration of other BCI stakeholders such as medical technology experts, caregivers, or health care professionals. The majority of the studies employ quantitative methods. Recurring themes across the studies examined were general user opinion towards BCI, central technical or social issues reported, requests/demands made by users of the technology, the potential/future of BCIs, and ethical aspects of BCIs. Our findings indicate that while technical aspects of BCIs such as usability or feasibility are being studied extensively, comparatively little in-depth research has been done on the self-image and self-experience of the BCI user. In general there is also a lack of focus or examination of the caregiver’s perspective. (shrink)

Philosophical arguments often assume that the folk tends towards moral objectivism. Although recent psychological studies have indicated that lay persons’ attitudes to morality are best characterized in terms of non-objectivism-leaning pluralism, it has been maintained that the folk may be committed to moral objectivism _implicitly_. Since the studies conducted so far almost exclusively assessed subjects’ metaethical attitudes via explicit cognitions, the strength of this rebuttal remains unclear. The current study attempts to test the folk’s implicit metaethical commitments. We present results (...) of a newly developed Implicit Association Test (IAT) for metaethical attitudes which indicate that the folk generally tend towards moral non-objectivism on the implicit level as well. We discuss implications of this finding for the philosophical debate. (shrink)

Transgender people have among the highest rates of suicide attempts of any group in society, driven strongly by the perception that they do not belong in the sex of their physical body. Gender reassignment surgery is a procedure that can change the transgender person’s physical body to accord with their gender identity. The procedure raises important ethical and distributive justice concerns, given the controversy of whether it is a cosmetic or medical procedure and the economic costs associated with performing the (...) procedure. This paper argues that there is a strong case for funding GRS as a matter of clinical necessity and justice. This paper will be divided in four key sections: First, the state of transgender health will be outlined, including the role of GRS and common objections to it. Second, a number of common objections to GRS will be analysed at the outset and shown to be unconvincing. Third, a constructive argument will be advanced, arguing that publicly funded GRS is clinically necessary, cost-effective, and demanded by principles of justice. Fourth, the paper will briefly discuss moralistic biases and why we demand a higher burden of justification for funding GRS compared with other analogous procedures. (shrink)

The essays in this book, by a variety of leading Augustine scholars, examine not only Augustine's multifaceted philosophy and its relation to his epoch-making theology, but also his practice as a philosopher, as well as his relation to other philosophers both before and after him. Thus the collection shows that Augustine's philosophy remains an influence and a provocation in a wide variety of settings today.

This research investigated the impact measures (such as lockdowns) used to combat the spread of the coronavirus disease of 2019 (COVID-19) have on the church’s mission. When people face travel and assembly restrictions, the church as a community of witnesses testifying and participating in Christ’s work risks is being neutralised, and its presence weakened. What then does mission as ‘being with’ look like in these situations? Is faithful presence something one can turn on and off at will depending on the (...) situation? If faithful presence was no more, what then was the impact of such absence on the church’s mission? These questions underscore the relevance of this research which sought to ascertain the impact the COVID-19 pandemic lockdown had on the church’s mission. The crucial area this research sought to explore are the lessons from the COVID-19 lockdown that will help the church prepare for future pandemics which scientists say are inevitable. The research made use of a qualitative interview method to discover the meaning of ‘being with’ in the context of the COVID-19 lockdown. The results revealed six attributes of a missional church. Based on these attributes, the research recommends a seven-step process to prepare the church for possible future pandemics.Contribution: This research has provided the church with an opportunity to shift from being ‘inward-looking’ to a church that is community focused, a church that prepares, trains and equips its adherents for the work of ministry in their own communities such that the work of ministry continues with or without gatherings. (shrink)

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)

ABSTRACTThis report on end‐of‐life decision‐making in Canada was produced by an international expert panel and commissioned by the Royal Society of Canada. It consists of five chapters.Chapter 1 reviews what is known about end‐of‐life care and opinions about assisted dying in Canada.Chapter 2 reviews the legal status quo in Canada with regard to various forms of assisted death.Chapter 3 reviews ethical issues pertaining to assisted death. The analysis is grounded in core values central to Canada's constitutional order.Chapter 4 reviews the (...) experiences had in a number of jurisdictions that have decriminalized or recently reviewed assisted dying in some shape or form.Chapter 5 provides recommendations with regard to the provision of palliative care in Canada, as well as recommendations for reform with respect to the various forms of assisted death covered in this document. (shrink)

Schelling’s masterpiece investigating evil and freedom.

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)

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)

The main premise of the Royal Dutch Medical Association's (RDMA) guideline on palliative sedation is that palliative sedation, contrary to euthanasia, is normal medical practice. Although we do not deny the ethical distinctions between euthanasia and palliative sedation, we will critically analyse the guideline's argumentation strategy with which euthanasia is demarcated from palliative sedation. First, we will analyse the guideline's main premise, which entails that palliative sedation is normal medical treatment. After this, we will critically discuss three crucial propositions of (...) the guideline that are used to support this premise: (1) the patient's life expectancy should not exceed 2 weeks; (2) the aim of the physician should be to relieve suffering and (3) expert consultation is optional. We will conclude that, if inherent problematic aspects of palliative sedation are taken seriously, palliative sedation is less normal than it is now depicted in the guideline. (shrink)

Society’s relationship with modern animal farming is an ambivalent one: on the one hand there is rising criticism about modern animal farming; on the other hand people appreciate certain aspects of it, such as increased food safety and low food prices. This ambivalence reflects the two faces of modernity: the negative (exploitation of nature and loss of traditions) and the positive (progress, convenience, and efficiency). This article draws on a national survey carried out in the Netherlands that aimed at gaining (...) a deeper understanding about the acceptance of modern dairy farming in Dutch society. People take two dimensions into account when evaluating different aspects of modern dairy farming: (1) the way living beings are used for production and (2) the way a dairy farm functions as a business. In both these dimensions people appeared to adopt cautious opinions: most people preferred relatively traditional and natural farms and were concerned about the use of nature and treatment of animals in modern production—although this did not imply an outright rejection of modern animal farming. The study also looked for (and sought to explain) differences of opinion between social groups. Besides socio-demographic factors such as age and gender, farming experience and value-orientation (such as socially minded and professional) appeared to be important variables. The values and convictions within modern society can help to explain why some people are greatly concerned about animal welfare while some show less concern. This diversity also helps to explain why general information campaigns are quite ineffective in allaying concerns about modern animal farming. (shrink)

An increasing number of older patients have to decide on a treatment plan for advanced chronic kidney disease, involving dialysis or conservative care. Shared decision-making is recommended as the model for decision-making in such preference-sensitive decisions. The aim of SDM is to come to decisions that are consistent with the patient’s values and preferences and made by the patient and healthcare professional working together. In clinical practice, however, SDM appears to be not yet routine and needs further implementation. A shift (...) from a biomedical to a person-centered conception might help to make the process more shared. Shared should, therefore, be interpreted as two persons bringing two perspectives to the table, that both need to be explored during the decision-making process. Starting from the patient’s perspective will enable to determine the mutual goals of care first and, subsequently, determine the best way for achieving those goals. To perform such SDM, the healthcare professional needs to become a skilled companion, being part of the patient’s relational context, and start asking the right questions about what matters to the patient as person. In this article, we describe the need for a person-centered conception of SDM for the setting of older patients with advanced CKD. (shrink)

This book traces the historical roots of the cognitive sciences and examines pre-modern conceptualizations of the mind as presented and discussed in the tradition of commentaries on Aristotle's De anima from 1200 until 1650. It explores medieval and Renai.

Background In the EU, clinical assessors, rapporteurs and the Committee for Medicinal Products for Human Use are obliged to assess the ethical aspects of a clinical development program and include major ethical flaws in the marketing authorization deliberation processes. To this date, we know very little about the manner that these regulators put this obligation into action. In this paper, we intend to look into the manner and the extent that ethical issues discovered during inspection have reached the deliberation processes. (...) Methods To gather data, we used the Dutch Medicines Evaluation Board database and first searched for the inspections, and their accompanying site inspection reports and integrated inspection reports, related to central marketing authorization applications of drugs submitted to the European Medicines Agency from 2011 to 2015. We then extracted inspection findings that were purely of ethical nature, i.e., those that did not affect the benefit/risk balance of the study. Only findings graded at least major by the inspectorate were included. Lastly, to identify how many of the ethically relevant findings reach the application deliberation processes, we extracted the relevant joint response assessment reports and reviewed the sections that discussed inspection findings. Results From 2011 to 2015, there were 390 processed applications, of which 65 had inspection reports and integrated inspection reports accessible via the database of the Dutch Medicines Evaluation Board. Of the 65, we found ERFs in 37. The majority of the ERFs were graded as major and half of the time it was informed-consent related. A third of these findings were related to research ethics committee processes and requirements. Of the 37 inspections with ERFs, 30 were endorsed in the integrated inspection reports as generally GCP compliant. Day 150 joint response assessment reports and Day 180 list of outstanding issues were reviewed for all 37 inspections, and none of the ERFs were carried over in any of the assessment reports or list of outstanding issues. Conclusion None of the ethically relevant findings, all of which were graded as major or critical in integrated inspection reports, were explicitly carried over to the joint assessment reports. This calls for more transparency in EMA application deliberations on how ERFs are considered, if at all, in the decision-making processes. (shrink)

We introduce prime products as a generalization of ultraproducts for positive logic. Prime products are shown to satisfy a version of Łoś’s Theorem restricted to positive formulas, as well as the following variant of the Keisler Isomorphism Theorem: under the generalized continuum hypothesis, two models have the same positive theory if and only if they have isomorphic prime powers of ultrapowers.