Objectives To evaluate whether the requirement of “minimal risk and burden” for paediatric research without direct benefit to the subjects compromises the ability to obtain data necessary for improving paediatric care. To provide evidence-based reflections on the EU recommendation that allows for a higher level of risk. Design and setting Systematic analysis of the approval/rejection decisions made by the Dutch Central Committee on Research involving Human Subjects (CCMO). Review methods The analysis included 165 proposals for paediatric research without direct benefit (...) that were reviewed by the CCMO between January, 2000, and July, 2007. A separate, in-depth analysis of all drug studies included 18 early phase drug studies and nine other drug studies without direct benefit. Results 11 out of 165 studies were definitively rejected because the CCMO did not regard the risk and/or burden to be minimal. In three of these 11 cases (including two early phase drug studies) the requirement of minimal risk and burden was cited as the only reason for rejection. Four other early phase drug studies also involved risks and/or burdens that were not regarded to be minimal but were nevertheless approved. Conclusions The requirement of minimal risk and burden, aiming to protect research subjects, occasionally leads to rejection of protocols. Early phase drug studies relatively often do not comply with the requirement. Committees may find ways to approve important studies that formally should be rejected, but that is not a desirable solution. The regulatory framework should be revised to make such occasional exceptions to the requirement legitimate and transparent. (shrink)

Informed consent is a key condition for prenatal screening programmes to reach their aim of promoting reproductive autonomy. Reaching this aim is currently being challenged with the introduction of non-invasive prenatal testing (NIPT) in first-trimester prenatal screening programmes: amongst others its procedural ease—it only requires a blood draw and reaches high levels of reliability—might hinder women’s understanding that they should make a personal, informed decision about screening. We offer arguments for a renewed recognition and use of informed consent compared to (...) informed choice, and for a focus on value-consistent choices and personalized informational preferences. We argue for a three-step counselling model in which three decision moments are distinguished and differently addressed: (1) professionals explore women’s values concerning whether and why they wish to know whether their baby has a genetic disorder; (2) women receive layered medical-technical information and are asked to make a decision about screening; (3) during post-test counselling, women are supported in decision-making about the continuation or termination of their pregnancy. This model might also be applicable in other fields of genetic (pre-test) counselling, where techniques for expanding genome analysis and burdensome test-outcomes challenge counselling of patients. (shrink)

In the debate surrounding the introduction of non-invasive prenatal testing in prenatal screening programmes, the concept of routinisation is often used to refer to concerns and potential negative consequences of the test. A literature analysis shows that routinisation has many different meanings, which can be distinguished in three major versions of the concept. Each of these versions comprises several inter-related fears and concerns regarding prenatal screening and particularly regarding NIPT in three areas: informed choice, freedom to choose and consequences for (...) people with a disability. Three of the strongest arguments raised under the flag of routinisation are assessed for their validity: the threat that NIPT poses to informed choice, the potential increase in uptake of first-trimester prenatal screening and its consequences for social pressure to participate in screening or terminate affected pregnancies, and the negative consequences for disabled people. These routinisation arguments lack empirical or normative ground. However, the results of this analysis do not imply that no attention should be paid to possible problems surrounding the introduction of NIPT. At least two problems remain and should be addressed: there should be an ongoing debate about the requirements of informed choice, particularly related to an expanded scope of prenatal screening. Also, reproductive autonomy can only be achieved when expecting parents’ options are variegated, real and valuable, so that they can continue to choose whether or not to screen or to terminate a pregnancy. (shrink)

Studie over de morele toelaatbaarheid van medische experimenten met mensen.

The central idea of this “article” is that certain developments such as extreme simplification, the politicisation of medical ethics, the “normative industry” and “empirethics”, may seriously threaten the (future) practice of medical ethics.

PART 9: GRAVITY'S ETHICSThis isn't a hospital! It's an insane asylum! And it's your fault! Shaking her head lightly, Doctor Van Tintelen leaves the room and softly closes the door. Empathy streaming through her veins, she never gets used to the unpolished grief of a patient she has to tell of inevitable death, never. She thinks, “There should be pipes to drain the tears in every room, or at least rinsing basins for grief. What a job.” The crying is that (...) of the sisters Barrio. Miranda and Monica are twins who always refer to themselves as M&M. Though Monica cries the hardest, it is Miranda who was just told that her breast cancer has spread into her liver. No more treatment available.“Don't cry, Monica, I took the risk purposely. We both knew breast cancer runs in our family. You had the test, I didn't.”“And now you see the result, Miranda, you are going to die. We aren't even fifty yet. Damn.” The irony is that the clock in the room doesn't work, its pointers silent and stiff.“Do you really think you are better off? I've never completely understood why you had the preventive double mastectomy.”“I have never felt less of a woman. You know that.”“I know, but some men felt differently about it.”The remark hurts Monica almost physically, and Miranda apologises immediately. “Sorry, sweetheart, I shouldn't have said that. The sisters embrace for the hundredth time.”“Maybe I was too much of a coward,” Miranda says, resigned, “or too proud of my breasts.” For a second she lifts the big breasts sadly with her hands. Cynically: “After all, they were my trumps in eroland.”“A coward? You? How about me?” Monica seems to calm down somewhat. “I was too afraid of the continual fear …. (shrink)

Part 10: The very old man and the sea of tears‘There is no time to waste, then, is there?' ‘He needs to be treated.’‘But he is 79 years old.’Two doctors in conflict. As happens often. The subject of the conversation is Mr Tyson, admitted to the hospital because of an aneurysm in his abdomen. Sarah Walters said ‘treat’. ‘Nonsense, too old, too risky’ is the opinion of Dr Jones. The squabble continues.Sarah: ‘So what? Does old age exclude you from society? (...) Of course we have to treat him.’‘But the investment will only last for a few years, and think of the risks, he may die from the operation. He should go home and, well, live what there is to live.’She shakes her head, her hair giving her a red aura. ‘I think he ought to have the operation.’‘I think it would be best if he should accept that time is running out, that life is finite, the whole existential rigmarole, et cetera.’‘Quite presumptuous of you to think he has not accepted that. Why? Just because he is old and did not kill himself?’ Sarah is indignant. ‘If he had done just that, we would have lamented about how we do not take care of our elderly, that society doesn't care, and that certainly there is no right to die unless your situation is totally hopeless and you're in a lot of pain. It doesn't make sense; in public health one does everything to increase life expectancy. Countries are proudly comparing themselves on the life expectancy list: mine is longer than yours. We worry because people have these unhealthy lifestyles, they are obese, they smoke, they get no exercise and they live a couch potato life. And then, lo and behold, they do grow old, in fact, and we go: …. (shrink)

The introduction of non-invasive prenatal testing in healthcare systems around the world offers an opportunity to reconsider funding policies for prenatal screening. In some countries with universal access healthcare systems, pregnant women and their partners are asked to pay for NIPT. In this paper, we discuss two important rationales for charging women for NIPT: to prevent increased uptake of NIPT and to promote informed choice. First, given the aim of prenatal screening, high or low uptake rates are not intrinsically desirable (...) or undesirable. Using funding policies to negatively affect uptake, however, is at odds with the aim of screening. Furthermore, copayment disproportionally affects those of lower socioeconomic status, which conflicts with justice requirements and impedes equal access to prenatal screening. Second, we argue that although payment models may influence pregnant women’s choice behaviours and perceptions of the relevance of NIPT, the copayment requirement does not necessarily lead to better-informed choices. On the contrary, external influences on women’s personal choices for or against prenatal screening should ideally be avoided. To improve informed decision-making, healthcare systems should instead invest in adequate non-directive, value-focused pretest counselling. This paper concludes that requiring copayments for NIPT in universal access healthcare systems fails to promote reproductive autonomy and is unfair. (shrink)

The American Journal of Bioethics, Volume 11, Issue 6, Page 29-31, June 2011.

As thousands of healthy research participants are being included in small and large imaging studies, it is essential that dilemmas raised by the detection of incidental findings are adequately handled. Current ethical guidance indicates that pathways for dealing with incidental findings should be in place, but does not specify what such pathways should look like. Building on an interview study of researchers’ practices and perspectives, we identified key considerations for the set-up of pathways for the detection, management and communication of (...) incidental findings in imaging research. We conducted an interview study with a purposive sample of researchers at research facilities across the Netherlands. Based on a qualitative analysis of these interviews and on existing guidelines found in the literature, we developed a prototype ethical framework, which was critically assessed and fine-tuned during a two-day international expert meeting with bioethicists and representatives from large population-based imaging studies from the United Kingdom, Germany, Sweden and Belgium. Practices and policies for the handling of incidental findings vary strongly across the Netherlands, ranging from no review of research scans and limited feedback to research participants, to routine review of scans and the arrangement of clinical follow-up. Respondents felt that researchers do not have a duty to actively look for incidental findings, but they do have a duty to act on findings, when detected. The principle of reciprocity featured prominently in our interviews and expert meeting. We present an ethical framework that may guide researchers and research ethics committees in the design and/or evaluation of appropriate pathways for the handling of incidental findings in imaging studies. The framework consists of seven steps: anticipation of findings, information provision and informed consent, scan acquisition, review of scans, consultation on detected abnormalities, communication of the finding, and further clinical management and follow-up of the research participant. Each of these steps represents a key decision to be made by researchers, which should be justified not only with reference to costs and/or logistical considerations, but also with reference to researchers’ moral obligations and the principle of reciprocity. (shrink)

This interview study investigates the short- and long-term implications of incidental findings detected through brain imaging on research participants’ lives and their surroundings. For this study, nine participants of the Rotterdam Scan Study with an incidental finding were approached and interviewed. When examining research participants’ narratives on the impact of the disclosure of incidental findings, the authors identified five sets of tensions with regard to motivations for and expectations of research participation, preferences regarding disclosure, short- and long-term impacts and impacts (...) on self and others. The paper shows: that the impact of incidental findings may be greater than participants at first let on; incidental findings can have significant effects on participants’ social environment; and participants may not feel prepared for disclosure even if incidental findings have been discussed during the informed consent process. The authors call for investigators to be aware of research participants’ experiences and these short- and long-term impacts when designing suitable courses of action for the detection and management of incidental findings in research settings. (shrink)

Part 12: The fall of the house of ethics‘Sometimes a cliché is the best way to make ones point’From: Whatever works.For some seconds Gordon is blinded by the lights the television crews direct at him. More than 20 cameras focus on him, and one journalist yells “there he is!” Even Gordon is not used to that much attention, but vanity is a speedy advisor. Within seconds he has clad himself in the aura of important person, and knowledgeable ethicist, even if (...) he has no idea what that many journalists expect from him at precisely this moment. Particularly when he has little time, preparing for the world conference on bioethics in Singapore. Then a wave of disappointment hits the gathered gossip-mongering press. The floodlights are turned off, microphones are lowered, the buzzing quiets down.“Guys, this is not Testosterone Tony.”This Tony, the athlete who participated in the Olympic Games in Beijing, at that moment leaves the hospital by a back door, far away from the paparazzi. The armoured car of his sponsor Nanosock disappears from sight softly humming and brings him to a private clinic where he will be pampered and detoxified. His career in sports is over, but his reputation can certainly sell sports socks with nanofibres against sweaty feet. The only price he has to pay is to admit he has sweaty feet, not true, but a small price to pay considering the alternatives. In front of the hospital the disappointed and somewhat offended Gordon tries to save his ego and asks the journalists:“Maybe I can be of help? Do you want an ethical analysis of Testosterone Tony and enhancing evolution? My name is Gordon Mc….” Nobody listens, nobody reacts.A day later. Nurses Jake and Gwen return from the medication round. Jake looks at the unlit room in the Nuttree …. (shrink)

Given the plethora of weight loss interventions, Devine and Barnhill rightly propose to also investigate unintended consequences. I agree. Some questions need to be raised: unintended consequences is a messy concept. How to distinguish between surprises and pseudo-unintended consequences? How to make sure that such research is not a box-ticking formality? And will results be implemented?

It is usually assumed that Apuleius gave one of his characters the name ‘Thrasyllus’ because of its etymological connection with θρασ. Indeed it is singularly appropriate and Apuleius himself draws attention to the fact: Thrasyllus, praeceps alioquin et de ipso nomine temerarius… . However, it does not follow that a name with such an etymological significance can have no other connotations: in this note I suggest that there is a further frame of reference behind ‘Thrasyllus’ and that Apuleius may have (...) expected his readers to realize this. (shrink)

It is usually assumed that Apuleius gave one of his characters the name ‘Thrasyllus’ because of its etymological connection with θρασ. Indeed it is singularly appropriate and Apuleius himself draws attention to the fact:Thrasyllus, praeceps alioquin et de ipso nomine temerarius…. However, it does not follow that a name with such an etymological significance can have no other connotations: in this note I suggest that there is a further frame of reference behind ‘Thrasyllus’ and that Apuleius may have expected his (...) readers to realize this. (shrink)

© 2016 Regents of the University of California.The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 3,062 new measurements from 721 papers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as supersymmetric particles, heavy bosons, axions, dark photons, etc. All the particle properties and search limits are listed in Summary Tables. We also give numerous (...) tables, figures, formulae, and reviews of topics such as Higgs Boson Physics, Supersymmetry, Grand Unified Theories, Neutrino Mixing, Dark Energy, Dark Matter, Cosmology, Particle Detectors, Colliders, Probability and Statistics. Among the 117 reviews are many that are new or heavily revised, including those on Pentaquarks and Inflation. The complete Review is published online in a journal and on the website of the Particle Data Group. The printed PDG Book contains the Summary Tables and all review articles but no longer includes the detailed tables from the Particle Listings. A Booklet with the Summary Tables and abbreviated versions of some of the review articles is also available. (shrink)

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) uses the conceptualization of psychopathology to make psychiatric diagnoses operational. The use of explicit operational criteria appears to be based on an implicit neo-positivist epistemology. Operationalism involves an excessive focus on quantitative descriptions of behavior manifestations, contesting that psychopathology is understood as a deviation from the normal or the average in a given population. Consequently, the normal and the psychopathological become homogeneous. Our analysis investigates if this neo-positivist epistemology narrows (...) psychopathology conceptualization and endanger integration with the hybrid biopsychosocial model of psychiatry. Based on Georges Canguilhem’s theorization of a qualitative approach to the individual organism who is in a state of morbidity, we show that the (psychiatric) pathology also contains differences in quality. Moreover, that humans are norm-producing organisms that actively respond to changes in their internal and external environment. In this regard, the operationalization of mental disorders could include the normativity in humans, i.e., the ability to produce norms. We argue this will mitigate the one-sided psychopathology conceptualization and strengthen the relationship between psychiatric nosology and psychiatry’s hybrid biopsychosocial model. (shrink)

The majority of Dutch physicians feel pressure when dealing with a request for euthanasia or physician-assisted suicide. This study aimed to explore the content of this pressure as experienced by general practitioners. We conducted semistructured in-depth interviews with 15 Dutch GPs, focusing on actual cases. The interviews were transcribed and analysed with use of the framework method. Six categories of pressure GPs experienced in dealing with EAS requests were revealed: emotional blackmail, control and direction by others, doubts about fulfilling the (...) criteria, counterpressure by patient’s relatives, time pressure around referred patients and organisational pressure. We conclude that the pressure can be attributable to the patient–physician relationship and/or the relationship between the physician and the patient’s relative, the inherent complexity of the decision itself and the circumstances under which the decision has to be made. To prevent physicians to cross their personal boundaries in dealing with EAS request all these different sources of pressure will have to be taken into account. (shrink)

Building on the long-standing tradition of challenging oppression and questioning whose interests are being served in the field of language education, we report on a study that involved a group of U.S.-based graduate students who collaborated with a ninth-grade English teacher in Nepal. The study comes out of a larger project that sought to internationalize the curriculum of a graduate educational linguistics course at a U.S. university. At the heart of this internationalizing curriculum endeavour was a commitment to expose graduate (...) students in the U.S. to the issues of language teaching outside of the U.S. This was done through co-designing of a unit of lessons, with six graduate students meeting virtually with their teacher partner, Ditya, in Nepal over the course of a semester. The graduate students and Ditya constitute our research participants. The graduate student participants learned about the need to develop pedagogical materials that were relevant to the local context in Nepali classroom, and not attempt to transplant a Western-centric curriculum onto the Nepali classroom. In keeping with recent calls to decolonize higher education, we illustrate how critical theory in general and decolonizing pedagogy in particular can be infused into a U.S. graduate curriculum by drawing on the rich, indigenous knowledge and resources of a teacher collaborator from the Global South. We do this by reporting how this critical, decolonizing goal was realized through collaborative professionalism, which is characterized by the sharing of knowledge, skills, and experience to improve student achievement, reflection, dialogue and collective responsibility. (shrink)

Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between (...) studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice. (shrink)

Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between (...) studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice. (shrink)

El texto que presentamos recoge las principales conclusiones que han derivado de los estudios sobre la Colección de documentos árabes del Archivo Histórico Provincial de Granada. Compuesta principalmente por documentos de carácter jurídico, el análisis del contenido de cada uno de ellos en relación con la materialidad del soporte y las tintas así como la coincidencia en el diseño y planificación de la página revelan el uso de idénticos protocolos de ejecución. Esta investigación nos está permitiendo, además, establecer coincidencias relevantes (...) relacionadas con los procesos de elaboración del papel entre los últimos años de permanencia de los árabes en la Península Ibérica y los primeros tras la incorporación del territorio a la Corona de Castilla y, sobre todo, con el modo de ejecutar el documento de archivo en sus formas externa e interna. (shrink)

Dans cette contribution, nous présentons la base CLAPI développée au laboratoire ICAR dans le contexte de l’évolution des bases de données de langues parlées en France au cours des trente dernières années. Nous détaillons les deux composantes de CLAPI, l’archive de corpus de langue parlée en interaction audio et vidéo enregistrés dans des situations sociales naturelles variées, et la plateforme d’outils.L’usage et l’apport de CLAPI sont illustrés par deux études. L’une décrit comment la base peut être utilisée pour des travaux (...) de linguistique interactionnelle intégrant la multimodalité (« oh là là ») ; l’autre concerne une recherche combinant données et métadonnées (« trop »). L’article est aussi l’occasion d’un bilan plus général. La mise en perspective montre en effet qu’après la période des questions est venue celle des dilemmes. La période des questions, choix et décisions à toutes sortes de niveaux a accompagné la mise en place des bases de données. L’expérience permet maintenant de mesurer leurs indéniables apports en termes non seulement de quantité de données disponibles (et traitables grâce aux outils), mais aussi de qualité (comme conséquence des exigences de standardisation liées au partage des données). La période des dilemmes nous conduit à nous interroger sur les meilleurs choix à opérer aujourd’hui dans les relations entre la poursuite des recherches sur des corpus variés (et parfois sensibles) et les exigences des bases de données ouvertes. (shrink)

El texto que presentamos recoge las principales conclusiones que han derivado de los estudios sobre la Colección de documentos árabes del Archivo Histórico Provincial de Granada. Compuesta principalmente por documentos de carácter jurídico, el análisis del contenido de cada uno de ellos en relación con la materialidad del soporte y las tintas así como la coincidencia en el diseño y planificación de la página revelan el uso de idénticos protocolos de ejecución. Esta investigación nos está permitiendo, además, establecer coincidencias relevantes (...) relacionadas con los procesos de elaboración del papel entre los últimos años de permanencia de los árabes en la Península Ibérica y los primeros tras la incorporación del territorio a la Corona de Castilla y, sobre todo, con el modo de ejecutar el documento de archivo en sus formas externa e interna. (shrink)

Several themes can be identified in the commentaries. The first is that the climbing fibers may have more than one function; the second is that the climbing fibers provide sensory rather than motor signals. We accept the possibility that climbing fibers may have more than one function consequence(s)’ in the title. Until we know more about the function of the inhibitory input to the inferior olive from the cerebellar nuclei, which are motor structures, we have to keep open the possibility (...) that the climbing fiber signals can be a combination of sensory and motor signals. (shrink)

Here are the 18 guidance points contained in the UNAIDS document on Ethical Considerations in HIV Preventive Vaccine Research, reproduced by kind permission of the Joint United Nations Programme on HIV/AIDS.

On the ethics of extending human life: healthy people have a right to carry on livingHumanity has long demonstrated a paradoxical ambivalence concerning the extension of a healthy human lifespan. Modest health extension has been universally sought, whereas extreme health extension has been regarded as a snare and delusion—a dream beyond all others at first blush, but actually something we are better off without. The prevailing pace of biotechnological progress is bringing ever closer the day when humanity will be able (...) to act on the latter view by rejecting a clear and present opportunity for much longer healthy lives. Indeed, some biogerontologists contend that that day has already arrived, to the extent that our hesitation in embarking on a vigorous “war on ageing” is already delaying the point at which a cure for ageing will be developed. Here I consider whether our present caution concerning the wisdom of truly curing ageing is likely to survive the increased scrutiny that it will receive in coming years as a result of these technical advances. I conclude that it will not, because of its irreconcilability with values that are more deeply held by the large majority of humanity than any values that argue against the quest for a cure. I further conclude that all the major current reasons given for not curing ageing are mere crutches to help us cope with the immutability of ageing that we have been brought up to accept. Our failure to set aside such irrationality is already shortening potential longevity—quite probably of those already alive today—to a staggering degree. Once we realise this, our determination to consign human ageing to history will be second …. (shrink)