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)

Support from grandparents plays a role in mothers’ perinatal mental health. However, previous research on maternal mental health has mainly focused on influences of partner support or general social support and neglected the roles of grandparents. In this narrative review and meta-analysis, the scientific evidence on the association between grandparental support and maternal perinatal mental health is reviewed. Searches in PubMed, EMBASE, MEDLINE, Scopus, and PsycINFO yielded 11 empirical studies on N = 3381 participants, reporting on 35 effect sizes. A (...) multilevel approach to meta-analysis was applied to test the association between grandparental support and maternal mental health. The results showed a small, statistically significant association (r =.16; 95% CI: 0.09–0.25). A moderator test indicated that the association was stronger for studies reporting on support from the maternal grandmother in particular (r =.23; 95% CI: 0.06–0.29). Our findings suggest that involved grandparents, in particular mother’s own mother, constitute a protective factor for the development of maternal postpartum mental health problems. These findings have clear implications for interventions. Future studies should examine whether stimulating high-quality support from grandparents is a fruitful avenue for enhancing maternal postpartum mental health. (shrink)

ABSTRACTMajor depressive disorder is a prevalent condition with high relapse rates. There is evidence that cognitive reactivity is an important vulnerability factor for the recurrence of depression. Mindfulness-based interventions are designed to reduce relapse rates, with cognitive reactivity as one of the proposed working mechanisms. In a randomised controlled trial we compared the effect of mindfulness-based cognitive therapy with treatment-as-usual on cognitive reactivity in recurrently depressed patients. Depressive symptoms, cognitive reactivity, and mindfulness skills were assessed pre and post treatment. Patients (...) in the MBCT group reported a significantly greater reduction in cognitive reactivity than those in the TAU group. The reduction of cognitive reactivity appeared to mediate the association between MBCT/TAU and decrease of depressive symptoms, using pre and post scores. The current study provides evidence that MBCT reduces cognitive reactivity and preliminar... (shrink)

In 2004 a survey was conducted in the member states of the European Union designed to gain greater insight into the views on control strategies for foot and mouth disease, classical swine fever, and avian influenza with respect to the epidemiological, economic and social-ethical consequences of each of these animal diseases. This article presents the results of the social-ethical survey. A selection of stakeholders from each member state was asked to prioritize issues for the prevention and control of these diseases. (...) A majority of stakeholders chose preventive measures as the preferred issue. An analysis was done to determine whether there were differences in views expressed by stakeholders from member states with a history of recent epidemics and ones without such a history, and whether there were regional differences. There were no differences between member states with or without a history of recent epidemics. There were indeed regional differences between the priority orders from Northern and Southern Europe on the one hand, and from Eastern Europe on the other. (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)

A adoção de um catálogo constitucional de direitos e o fortalecimento do judicial review, trouxeram como consequência a judicialização da política em inúmeras democracias, onde se verifica uma expansão da atuação do Poder Judiciário em detrimento das esferas representativas do Estado. Neste contexto, tem se observado em países do Sul Global, o emprego de novos mecanismos procedimentais em casos que envolvem a violação contínua e generalizada de direitos fundamentais, de alguns grupos menos favorecidos, decorrente de bloqueios políticos e institucionais, denominados (...) de “litígios estruturais”. (shrink)

Sleep has a profound effect on our mood, but insight in the mechanisms underlying this association is still lacking. We tested whether emotion regulation is a mediator in the relationship between fragmented sleep and mood disturbance. The effect of fragmented sleep on the emotion regulation strategies, including cognitive reappraisal, distraction, acceptance and suppression ability, was assessed. We further tested whether the use of these strategies, as well as rumination and self-criticism, mediated the association between fragmented sleep and negative and positive (...) affect. Participants (N = 69) wore an actiwatch and filled in a sleep diary for 12 consecutive nights. They had one control night and one sleep fragmentation night. Emotion regulation ability was assessed with an experimental task. Usage of emotion regulation strategies and negative and positive affect were assessed four times during the day with a survey after the control and sleep fragmentation night. Cognitive reappraisal, distraction, acceptance and suppression ability did not differ between the sleep fragmentation and control condition. However, participants reported higher usage of rumination and distraction after the sleep fragmentation night and rumination significantly mediated the negative association between fragmented sleep and negative affect. (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)

BackgroundAdverse childhood experiences can cause serious mental problems in adolescents and therefore may expected to be associated with higher use of psychosocial care, potentially varying by type of specific ACE. The aim of our study is to explore the association of the number of ACE and types of specific ACE with entering and using psychosocial care.MethodsWe used data from the Slovak Care4Youth cohort study, comprising 509 adolescents from 10 to 16 years old. We used logistic regression models adjusted for age, (...) gender, and family affluence to explore the associations of number and type of specific ACE with the use of psychosocial care.ResultsHaving three or more ACE as well as experiencing some specific ACE increased the likelihood of using psychosocial care. Regarding experience with the death of somebody else you love, we found a decreased likelihood of the use of psychosocial care.ConclusionExperiencing ACE above a certain threshold and parent-related ACE increase the likelihood of adolescent care use. (shrink)

Progressive supranuclear palsy is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP and 3,247 controls followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the (...) stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved. (shrink)

Background Genuine uncertainty on superiority of one intervention over the other is called equipoise. Physician-investigators in randomized controlled trials need equipoise at least in studies with more than minimal risks. Ideally, this equipoise is also present in patient-participants. In pediatrics, data on equipoise are lacking. We hypothesize that 1) lack of equipoise at enrolment among parents may reduce recruitment; 2) lack of equipoise during participation may reduce retention in patients assigned to a less favoured treatment-strategy. Methods We compared preferences of (...) parents/patients at enrolment, documented by a questionnaire, with preferences developed during follow-up by an interview-study to investigate equipoise of child-participants and parents in the BeSt-for-Kids-study. This trial in new-onset Juvenile Idiopathic Arthritis-patients consists of three strategies. One strategy comprises initial treatment with a biological disease-modifying-antirheumatic-drug, currently not standard-of-care. Semi-structured interviews were conducted with 23 parents and 7 patients, median 11 months after enrolment. Results Initially most parents and children were not in equipoise. Parents/patients who refused participation, regularly declined due to specific preferences. Many participating families preferred the biological-first-strategy. They participated to have a chance for this initial treatment, and would even consider stopping trial-participation when not randomized for it. Their conviction of superiority of the biological-first strategy was based on knowledge from internet and close relations. According to four parents, the physician-investigator preferred the biological-first-strategy, but the majority stated that she had no preferred strategy. In phase 2, preferences tended to change to the treatment actually received. Conclusions Lack of equipoise during enrolment did not reduce study recruitment, mainly due to the fact that preferred treatment was only available within the study. Still, when developing a trial it is important to evaluate whether the physicians’ research question is in line with preferences of the patient-group. By exploring so-called ‘informed patient-group’-equipoise, successful recruitment may be enhanced and bias avoided. In our study, lack of equipoise during trial-participation did not reduce retention in those assigned to a less favoured option. We observed a change for preference towards treatment actually received, possibly explained by comparable outcomes in all three arms. (shrink)

The current study investigates whether self-talk phrases can influence behavior in Ultimatum Games. In our three self-talk treatments, participants were instructed to tell themselves (i) to keep their own interests in mind, (ii) to also think of the other person, or (iii) to take some time to contemplate their decision. We investigate how such so-called experimenter-determined strategic self-talk phrases affect behavior and emotions in comparison to a control treatment without instructed self-talk. The results demonstrate that other-focused self-talk can nudge proposers (...) towards fair behavior, as offers were higher in this group than in the other conditions. For responders, self-talk tended to increase acceptance rates of unfair offers as compared to the condition without self-talk. This effect is significant for both other-focused and contemplation-inducing self-talk but not for self-focused self-talk. In the self-focused condition, responders were most dissatisfied with unfair offers. These findings suggest that use of self-talk can increase acceptance rates in responders, and that focusing on personal interests can undermine this effect as it negatively impacts the responders’ emotional experience. In sum, our study shows that strategic self-talk interventions can be used to affect behavior in bargaining situations. (shrink)

In this article, an ethical analysis of an educational programme on renal replacement therapy options for patients and their social network is presented. The two main spearheads of this approach are: (1) offering an educational programme on all renal replacement therapy options ahead of treatment requirement and (2) a home-based approach involving the family and friends of the patient. Arguments are offered for the ethical justification of this approach by considering the viewpoint of the various stakeholders involved. Finally, reflecting on (...) these ethical considerations, essential conditions for carrying out such a programme are outlined. The goal is to develop an ethically justified and responsible educational programme. (shrink)

Dutch investigators continue to play a key role in animal behavior studies today . The present collection of current Dutch writings on animal consciousness ...

In spite of his post-World War II works on international law, which seems more purely juridical, Hans Kelsen continues to put forward in his vast body of work an implicit – and sometimes even explicit – juridical objectivism and pacifism. Especially before and during the second World War he makes – by means of many moral-political writings – an effort for a more effective assurance of international peace. The fact that Kelsen regards the law as the pre-eminent means to achieve (...) the end of peace, is – in view of the tradition running from Hobbes to Kant – still not very innovating. But the primary and central role he assigns to the judiciary in order to guarantee international peace is on the other hand really original. To bring out Kelsen’s juridical objectivism and pacifism, I restrict myself in this article to his plea before and during the second World War for the judicial primacy in the international legal order. In that plea, which is spread over many writings and founded by several arguments, I distinguish however three main convincing arguments – namely an evolutionary, a technical and a moral-political argument – for the establishment of an international court with compulsory jurisdiction as the ‘guardian of international peace’. The fact that Kelsen’s original plea is still relevant to our times, is already evident from the post-World War II UN-system of peace-enforcement, which still functions little satisfactorily and of which the existing plans of reform go no further than strengthening the position of the Security Council, the current hardly effective ‘maintainer of world peace’. (shrink)

— We prescnt here a comparative study on the decay of chlorophyll a fluorescence yield in thylakoid membranes and photosystem 11 ‐enriched samples, measured with multifrequency cross‐correlation phase fluorometry. These measurements confirm the general conclusions of Van Mieghem ef al., obtained with a flash method, on the effects of reduction of the primary quinone acceptor on ChI a fluorescence yield of PSI. Different states of the reaction centers of PSII were produced by: pretreatment with sodium dithionite and mcthyl viologen followed (...) by laser illumination: the doubly reduced QA centers: with laser illumination or pretreatment with diuron: QA‐ centers; and the addition of micromolar concentration of dichlorobenzoquinonc : oxidized QA centers. The data were analyzed with Lorentzian distribution as well as with multiexponential fluorescence decay functions. The analysis with Lorcntzian distribution function showed that upon formation of QA. the major lifetime distribution peak shifted to longer lifetimes: from 0.25 ns to 1.66 ns and from 0.24 ns to 1.31 ns. However, when QAHZ was formed, the lifetime distribution peaks shifted back to shorter lifetimes both in thylakoids and PSIl membranes. Multiexponential analysis showed three lifetime components: fast, middle and slow. When QA was formed in PS11 centers, the amplitude of the fast Component decreased, but both thc amplitude and the lifetime of the middle component increased severalfold. However, when QA was doubly reduccd, the amplitude of the fast component increased and the amplitude of the middle component decreased: in addition, the lifetime of the slow component increased. All of the above results are consistent with the conclusions that PS11 charge separation is decreased when QA is formed and increased when doubly reduced QA is formed. Copyright © 1993, Wiley Blackwell. All rights reserved. (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)