Degradation of eukaryotic RNAs that contain premature termination codons (PTC) during nonsense‐mediated mRNA decay (NMD) is initiated by RNA decapping or endonucleolytic cleavage driven by conserved factors. Models for NMD mechanisms, including recognition of PTCs or the timing and role of protein phosphorylation for RNA degradation are challenged by new results. For example, the depletion of the SMG5/7 heterodimer, thought to activate RNA degradation by decapping, leads to a phenotype showing a defect of endonucleolytic activity of NMD complexes. (...) This phenotype is not correlated to a decreased binding of the endonuclease SMG6 with the core NMD factor UPF1, suggesting that it is the result of an imbalance between active (e.g., in polysomes) and inactive (e.g., in RNA‐protein condensates) states of NMD complexes. Such imbalance between multiple complexes is not restricted to NMD and should be taken into account when establishing causal links between gene function perturbation and observed phenotypes. (shrink)

The multistep pathway of eukaryotic gene expression involves a series of highly regulated events in the nucleus and cytoplasm. In the nucleus, genes are transcribed into pre‐messenger RNAs which undergo a series of nuclear processing steps. Mature mRNAs are then transported to the cytoplasm, where they are translated into protein and degraded at a rate dictated by transcript‐ and cell‐type‐specific cues. Until recently, these individual nuclear and cytoplasmic events were thought to be primarily regulated by different RNA‐ and DNA‐binding proteins (...) that are localized either only in the nucleus or only the cytoplasm. Here, we describe multifunctional proteins that control both nuclear and cytoplasmic steps of gene expression. One such class of multifunctional proteins (e.g., Bicoid and Y‐box proteins) regulates both transcription and translation whereas another class (e.g., Sex‐lethal) regulates both nuclear RNA processing and translation. Other events controlled by multifunctional proteins include assembly of spliceosome components, spliceosome recycling, RNA editing, cytoplasmic mRNA localization, and cytoplasmic RNA stability. The existence of multifunctional proteins may explain the paradoxical involvement of the nucleus in an RNA surveillance pathway (nonsense‐mediated decay) that detects cytoplasmic signals (premature termination codons). We speculate that shuttling multifunctional proteins serve to efficiently link RNA metabolism in the cytoplasmic and nuclear compartments. BioEssays 23:775–787, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Clinical trials give rise to ethical dilemmas, especially in the acutely ill, but we take issue with two points raised in a recent comment on a specific acute myocardial infarction (AMI) trial. The commentators judged that the trial most likely could, and therefore should, have been terminated much earlier. By analysing the problem statistically we arrive at results that go against their intuitive judgment—they also see it as mandatory to update the patient Information sheet as trial results accrue and trends (...) begin to emerge. In our view, interpreting subtle trends and borderline p-values must rest with data monitoring boards, not patients. Moreover, patients with AMI or in other medical emergencies need very simple instructions. Empirical studies of the consent process confirm that the idea of a genuinely informed consent is problematic in such cases. (shrink)

Background: Due to recent legislations on euthanasia and its current practice in the Netherlands and Belgium, issues of end-of-life medicine have become very vital in many European countries. In 2002, the Ethics Working Group of the German Association for Palliative Medicine (DGP) has conducted a survey among its physician members in order to evaluate their attitudes towards different end-of-life medical practices, such as euthanasia (EUT), physician-assisted suicide (PAS), and terminal sedation (TS). Methods: An anonymous questionnaire was sent to the 411 (...) DGP physicians, consisting of 14 multiple choice questions on positions that might be adopted in different hypothetical scenarios on situations of “intolerable suffering” in end-of-life care. For the sake of clarification, several definitions and legal judgements of different terms used in the German debate on premature termination of life were included. For statistical analysis t-tests and Pearson-correlations were used. Results: The response rate was 61% (n=251). The proportions of the respondents who were opposed to legalizing different forms of premature termination of life were: 90% opposed to EUT, 75% to PAS, 94% to PAS for psychiatric patients. Terminal sedation was accepted by 94% of the members. The main decisional bases drawn on for the answers were personal ethical values, professional experience with palliative care, knowledge of alternative approaches, knowledge of ethical guidelines and of the national legal frame. Conclusions: In sharp contrast to similar surveys conducted in other countries, only a minority of 9.6% of the DGP physicians supported the legalization of EUT. The misuse of medical knowledge for inhumane killing in the Nazi period did not play a relevant role for the respondents’ negative attitude towards EUT. Palliative care needs to be stronger established and promoted within the German health care system in order to improve the quality of end-of-life situations which subsequently is expected to lead to decreasing requests for EUT by terminally ill patients. (shrink)

Abortion is permitted in many jurisdictions after the age at which an infant is viable on the basis of intensive neonatal care techniques. Does this cause special concerns for those involved in perinatal care and termination of pregnancy services or is the overlap mainly an abstract issue fretted over by ethicists and academics? In order to explore this question, a group of clinicians involved in this area of care were interviewed and their interviews analysed using qualitative measures. The clinicians (...) concerned were exercised by the ethical issues and had various ways of resolving them which tended to reflect a gradualist, multifaceted and, to some extent, particularist approach to ethical decision-making in relation to the edges of human life. The ways in which those strands of ethical thought are instanced in the interview material are reported and discussed. (shrink)

BackgroundThe terminal illness of late-stage Alzheimer’s and related dementias is progressively cruel, burdensome, and can last years if caregivers assist oral feeding and hydrating. Options to avoid prolonged dying are limited since advanced dementia patients cannot qualify for Medical Aid in Dying. Physicians and judges can insist on clear and convincing evidence that the patient wants to die—which many advance directives cannot provide. Proxies/agents’ substituted judgment may not be concordant with patients’ requests. While advance directives can be patients’ last resort (...) to attain a peaceful and timely dying consistent with their lifelong values, success depends on their being effective and acceptable. A single flaw can provide opponents justification to refuse the directive’s requests to cease assisted feeding.AimThis article considers 24 common advance directive flaws in four categories. Process flaws focus on how patients express their end-of-life wishes. Content flaws reflect drafters’ selection of conditions and interventions, and how they are described. Inherent flaws can make advance directives unacceptable to authorities concerned about premature dying. Strategies are needed to compel physicians to write needed orders and to prevent third parties from sabotaging these orders after they are implemented. The article includes excerpts from “dementia-specific” directives or supplements that exemplify each flaw—mostly from the US and Europe. No directive critiqued here included an effective strategy to resolve this long-debated bioethical conflict: the past directive requests “Cease assisted feeding” but the incapacitated patient apparently expresses the desire to “Continue assisted feeding.” Some opponents to the controversial request, cease assisted feeding, use this conflict as a conceptual wedge to practice hard paternalism. This article proposes a protocol to prevent this conflict from emerging. These strategies may prevent authorities from requiring patients to fulfill authorities’ additional clinical criteria as a prerequisite to honor the requests in patients directives.ConclusionThis critique of flaws may serve as a guide to drafting and to selecting effective and acceptable advance directives for dementia. It also poses several bioethical and clinical questions to those in authority: Does your paternalistic refusal to honor patients’ wishes respect their self-determination? Protect vulnerable patients from harm? Force patients to endure prolonged suffering? Violate the principles of bioethics? Violate the very foundation of patient-centered care? (shrink)

Regulation of gene expression by premature termination of transcription, or transcription attenuation, is a common regulatory strategy in bacteria. Various mechanisms of regulating transcription termination have been uncovered, each can be placed in either of two broad categories of termination events. Many mechanisms involve choosing between two alternative hairpin structures in an RNA transcript, with the decision dependent on interactions between ribosome and transcript, tRNA and transcript, or protein and transcript. In other examples, modification of the (...) transcription elongation complex is the crucial event. This article will describe and compare several of these regulatory strategies, and will cite specific examples to illustrate the different mechanisms employed. BioEssays 24:700–707, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

In the United Kingdom women have access to termination of pregnancy for maternal reasons until 24 weeks’ completed gestation, but it is accepted practice for children born at or beyond 25 weeks’ gestation to be treated according to the child’s perceived best interests even if this is not in accordance with parental wishes. The authors present a case drawn from clinical practice which highlights the discomfort that parents may feel about such an abrupt change in their rights over their (...) child, and argue that parents should have greater autonomy over treatment decisions regarding their prematurely born children. (shrink)

Current research in Explainable AI includes post-hoc explanation methods that focus on building transparent explaining agents able to emulate opaque ones. Such agents are naturally required to be accurate and trustworthy. However, what it means for an explaining agent to be accurate and trustworthy is far from being clear. We characterize accuracy and trustworthiness as measures of the distance between the formal properties of a given opaque system and those of its transparent explanantes. To this aim, we extend Probabilistic Computation (...) Tree Logic with operators to specify degrees of accuracy and trustworthiness of explaining agents. We also provide a semantics for this logic, based on a multi-agent structure and relative model-checking algorithms. The paper concludes with a simple example of a possible application. (shrink)

Name der Zeitschrift: Byzantinische Zeitschrift Jahrgang: 111 Heft: 1 Seiten: 157-212.

The high predictive accuracy of contemporary machine learning-based AI systems has led some scholars to argue that, in certain cases, we should grant them epistemic expertise and authority over humans. This approach suggests that humans would have the epistemic obligation of relying on the predictions of a highly accurate AI system. Contrary to this view, in this work we claim that it is not possible to endow AI systems with a genuine account of epistemic expertise. In fact, relying on accounts (...) of expertise and authority from virtue epistemology, we show that epistemic expertise requires a relation with understanding that AI systems do not satisfy and intellectual abilities that these systems do not manifest. However, recent developments of large language models make us argue that in the future AI systems may endowed with a form of epistemic authority. Further, following the Distributed Cognition theory and adapting an account by Croce on the virtues of collective epistemic agents to the case of human-AI interactions we show that, if an AI system is successfully appropriated by a human agent, a hybrid epistemic agent emerges, which can become both an epistemic expert and an authority. Consequently, we claim that the aforementioned hybrid agent is the appropriate object of a discourse around trust in AI and the epistemic obligations that stem from its epistemic superiority. (shrink)

Human-centered explainable AI (HCXAI) advocates for the integration of social aspects into AI explanations. Central to the HCXAI discourse is the Social Transparency (ST) framework, which aims to make the socio-organizational context of AI systems accessible to their users. In this work, we suggest extending the ST framework to address the risks of social misattributions in Large Language Models (LLMs), particularly in sensitive areas like mental health. In fact LLMs, which are remarkably capable of simulating roles and personas, may lead (...) to mismatches between designers' intentions and users' perceptions of social attributes, risking to promote emotional manipulation and dangerous behaviors, cases of epistemic injustice, and unwarranted trust. To address these issues, we propose enhancing the ST framework with a fifth 'W-question' to clarify the specific social attributions assigned to LLMs by its designers and users. This addition aims to bridge the gap between LLM capabilities and user perceptions, promoting the ethically responsible development and use of LLM-based technology. (shrink)

Recent animal research suggests that it may soon be possible to support the human fetus in an artificial uterine environment for part of a pregnancy. A technique of extending gestation in this way (“ectogestation”) could be offered to parents of extremely premature infants (EPIs) to improve outcomes for their child. The use of artificial uteruses for ectogestation could generate ethical questions because of the technology’s potential impact on the point of “viability”—loosely defined as the stage of pregnancy beyond which (...) the fetus may survive external to the womb. Several medical decisions during the perinatal period are based on the gestation at which infants are considered viable, for example decisions about newborn resuscitation and abortion, and ectogestation has the potential to impact on these. Despite these possible implications, there is little existing evidence or analysis of how this technology would affect medical practice. In this paper, we combine empirical data with ethical analysis. We report a survey of 91 practicing Australian obstetricians and neonatologists; we aimed to assess their conceptual understanding of “viability,” and what ethical consequences they envisage arising from improved survival of EPIs. We also assess what the ethical implications of extending gestation should be for newborn and obstetric care. We analyze the concept of viability and argue that while ectogestation might have implications for the permissibility of neonatal life‐prolonging treatment at extremely early gestation, it should not necessarily have implications for abortion policy. We compare our ethical findings with the results of the survey. (shrink)

What does it mean to ‘drop out’ of therapy? Many definitions of ‘dropout’ have been proposed, but the most widely accepted is the client ending treatment without agreement of their therapist. However, this is in some ways an external criterion that does not take into account the client’s experience of therapy, or reasons for ending it prematurely. This study aimed to identify whether there were more meaningful categories of dropout than the existing dropout definition, and to test whether this refined (...) categorisation of dropout was associated with clinical outcomes. This mixed-methods study used a subset of data from the IMPACT trial, which investigated psychological therapies for adolescent depression. Adolescents were randomly allocated to a treatment arm (Brief Psychosocial Intervention; Cognitive-Behavioural Therapy; Short-Term Psychoanalytic Psychotherapy). The sample for this study comprised 99 adolescents, aged 11-17 years. 32 were classified as having dropped out of treatment and participated in post-therapy qualitative interviews about their experiences of therapy. For 26 dropout cases, the therapist was also interviewed. 67 cases classified as having completed treatment were included to compare their outcomes to dropout cases. Interview data for dropout cases were analysed using ideal type analysis. Three types of dropout were constructed: ‘dissatisfied’ dropout, ‘got-what-they-needed’ dropout, and ‘troubled’ dropout. ‘Dissatisfied’ dropouts reported stopping therapy because they did not find it helpful. ‘Got-what-they-needed’ dropouts reported stopping therapy because they felt they had benefitted from therapy. ‘Troubled’ dropouts reported stopping therapy because of a lack of stability in their lives. The findings indicate the importance of including the perspective of clients in definitions of drop out, as otherwise there is a risk that the heterogeneity of 'dropout' cases may mask more meaningful distinctions. Clinicians should be aware of the range of issues experienced by adolescents in treatment that lead to disengagement. Our typology of dropout may provide a framework for clinical decision-making in managing different types of disengagement from treatment. (shrink)

Nonsense‐mediated RNA decay (NMD) represents an established quality control checkpoint for gene expression that protects cells from consequences of gene mutations and errors during RNA biogenesis that lead to premature termination during translation. Characterization of NMD‐sensitive transcriptomes has revealed, however, that NMD targets not only aberrant transcripts but also a broad array of mRNA isoforms expressed from many endogenous genes. NMD is thus emerging as a master regulator that drives both fine and coarse adjustments in steady‐state RNA levels (...) in the cell. Importantly, while NMD activity is subject to autoregulation as a means to maintain homeostasis, modulation of the pathway by external cues provides a means to reprogram gene expression and drive important biological processes. Finally, the unanticipated observation that transcripts predicted to lack protein‐coding capacity are also sensitive to this translation‐dependent surveillance mechanism implicates NMD in regulating RNA function in new and diverse ways. (shrink)

The α‐actinins are an ancient family of actin‐binding proteins that play structural and regulatory roles in cytoskeletal organisation and muscle contraction. α‐actinin‐3 is the most‐highly specialised of the four mammalian α‐actinins, with its expression restricted largely to fast glycolytic fibres in skeletal muscle. Intriguingly, a significant proportion (∼18%) of the human population is totally deficient in α‐actinin‐3 due to homozygosity for a premature stop codon polymorphism (R577X) in the ACTN3 gene. Recent work in our laboratory has revealed a (...) strong association between R577X genotype and performance in a variety of athletic endeavours. We are currently exploring the function and evolutionary history of the ACTN3 gene and other α‐actinin family members. The α‐actinin family provides a fascinating case study in molecular evolution, illustrating phenomena such as functional redundancy in duplicate genes, the evolution of protein function, and the action of natural selection during recent human evolution. BioEssays 26:786–795, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

ABSTRACTHow accurate are insights compared to analytical solutions? In four experiments, we investigated how participants' solving strategies influenced their solution accuracies across different types of problems, including one that was linguistic, one that was visual and two that were mixed visual-linguistic. In each experiment, participants' self-judged insight solutions were, on average, more accurate than their analytic ones. We hypothesised that insight solutions have superior accuracy because they emerge into consciousness in an all-or-nothing fashion when the unconscious solving process is complete, (...) whereas analytic solutions can be guesses based on conscious, prematurely terminated, processing. This hypothesis is supported by the finding that participants' analytic solutions included relatively more incorrect responses than timeouts compared to their insight responses. (shrink)

Unlike the nontheological articles, this one must, for the sake of its coherence in this volume, define its basic discipline before its specific feminism can be articulated. Theology, “god‐word,” a term coined by the pagan Plato, became the language game of Christian intellectuals within a century of the death of Jesus of Nazareth. This Jewish life, its premature termination, and the virtually unprecedented spread of the spiritual movement he had initiated managed to attract philosophical minds such as Clement (...) of Alexandria and later, Augustine of Hippo, in the meantime converting the emperor as well. So the philosophical logos of the cultural elite established itself as the discourse of the Christian movement – hence theo‐logos. Indeed, the author of the fourth gospel had already identified Jesus himself as the incarnation of the cosmic logos, the principle of meaningful order for Stoicism, the Word of God for the Jews. This translation of Hebrew metaphor into Hellenistic philosophy prefigured the institutionalization of a set of rationalized symbols as the creeds (in Greek, symboloi) of Christendom. That institutionalization sought at once to organize Christian spirituality around belief, that is, around discursive propositions to which one assents or not; and to homogenize a tumultuous, subversive, and multifarious movement around the political expediency of unifying both Church and Empire. (shrink)

We formulate the following hypothesis: Life's origin may have occurred during the lower Archaean at a time when the environmental temperature was higher than it is at present. Preliminary consequences of this hypothesis are studied from the point of view of molecular evolution. We restrict our attention to implications regarding the genetic code. We conclude that alternative assignment of termination codons may be understood in terms of: (a) the elevated temperatures to which the progenote may initially have been exposed; (...) and (b) the subsequent response of its genome to the opportunity provided by the eventual loss of hyperthermal genetic expression during a thermal transition (TT) period, which was triggered off by the evolution of the dynamic Earth. (shrink)

Clinical Study Agreements can have profound effects both on the protection of human subjects and on the independence of investigators to conduct research with scientific integrity. Sponsors, institutions, and even investigators may fail to give adequate attention to these issues in the negotiation of CSAs. Despite the key role of CSAs in structuring ethically important aspects of research, they remain largely unregulated and unreviewed for adherence to ethical norms. Academic institutions routinely enter into research contracts that fail to meet adequate (...) ethical standards. This is a failing that can have serious consequences.Accordingly, it is necessary that some independent body have the authority both to review research contracts for compliance with norms of subject protection and ethical integrity, and to reject studies that fail to meet ethical standards. Such review should take place prior to the start of research, not later. Because of its expertise and authority, the institutional ethics review board is the appropriate body to undertake such review. Much recent commentary has focused on contractual restrictions on the investigator’s freedom to publish research findings. The Olivieri experience, and that of other investigators, has brought freedom of publication issues into sharp focus. Clinical study agreements also raise a number of other ethical issues relating to human subjects and research integrity, however, including disclosures relating to patient safety, data analysis and reporting, budget, confidentiality, and premature termination of the study. This paper describes the ethical issues at stake in structuring such agreements and suggests ethical standards to guide institutional ethics review. (shrink)

The expression of protein‐encoding genes is a complex process culminating in the production of mature mRNA and its translation by the ribosomes. The production of a mature mRNA involves an intricate series of processing steps. The majority of eukaryotic protein‐encoding genes contain intron sequences that disrupt the protein‐encoding frame, and hence have to be removed from immature mRNA prior to translation into protein. The mechanism involved in the selection of correct splice sites is incompletely understood. A considerable body of evidence (...) suggests that the splicing machinery has suboptimal efficiency and fidelity leading to substantial processing inaccuracy. Here we discuss a recently published article1 that extends observations that cells rely on nonsense‐mediated mRNA decay (NMD) to compensate for such suboptimal processing accuracy. Intriguingly these authors provide evidence for a strong selective pressure in favour of premature termination of mRNA translation in the event of intron retention. The analysis presented implies a positive role of NMD in transcript diversification through alternative splicing and suggest that this ancient surveillance mechanism may have co‐evolved with intron acquisition born from the need for quality control of splicing patterns. BioEssays 30:926–928, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

The article analyses the regulation for premature termination of the Parliament in Latvia. The introductory part of the article provides a short characteristic of the Constitution of Latvia - the Satversme adopted in 1922, and outlines the basic principles of legal regulation of the Parliament, i.e. the Saeima. Further chapters of the article analyse historic development of the premature termination of the Parliament. On 15 February, 1922, when the Satversme was adopted, only one mechanism for the (...) premature termination of the Parliament was established there: dissolution of the Saeima. However, relatively recently, in 2009, after a prolonged public discussion another mechanism for the premature termination of the activity of the Saeima was established, which was the recall.1 Both models of the termination of the activities of the Parliament are analysed in the article by specifying the principal differences between them. Along with the analysis of the provisions of the Constitution and theory, the practice of dissolution of the Saeima is characterised as well, because in 2011 the Parliament (the Saeima) was dissolved in a constitutional way for the first and so far the only time in the history of Latvia and extraordinary elections were held. (shrink)

During the last two decades there has been an enormous development in treatment possibilities in the field of neonatology, particularly for (extremely) premature infants. Although there are cross-cultural differences in treatment strategy, an overview of the literature suggests that every country is confronted with moral dilemmas in this area. These concern decisions to initiate or withhold treatment directly at birth and, later on, decisions to withdraw treatment with the possible consequence that the child will die. Given that the neonate (...) cannot express his or her own will, who will decide? And on the basis of what information, values and norms? We explored some of these issues in daily practice by interviewing a small sample of health care practitioners in a Dutch university Neonatal Intensive Care Unit (NICU). It turned out that experiencing moral dilemmas is part of their daily functioning. Nurses underline the suffering of the newborn, whereas physicians stress uncertainty in treatment outcome. To make the best of it, nurses focus on their caring task, whereas physicians hope that future follow-up research will lead to more predictable outcomes. As for their own offspring, part of these professionals would hesitate to bring their own extremely premature newborn to a NICU. For the most oppressing dilemma reported – terminating an already initiated treatment – we propose the concept of ‘evidence shift’ to clarify the ambiguous position of uncertainty in decision making. (shrink)

: Recent controversial decisions to terminate several large clinical trials have called attention to the need for developing a sound ethical framework to determine when trials should be stopped in light of emerging efficacy data. Currently, the fundamental rationale for stopping trials early is based on the principle that equipoise has been disturbed. We present an analysis of the ethical and practical problems with the "equipoise disturbed" position and describe an alternative ethical framework based on the principle of nonexploitation. This (...) framework acknowledges the need for balancing the dual ethical obligations of clinical research, the protection of human subjects and the generation of new medical knowledge. Based on this framework, we put forward a proposal to make early stopping guidelines more stringent under specified conditions. The temporary withholding of apparent benefits in certain circumstances is justified by achieving a fair contract with the research participants, one that protects them from undue harm and exploitation while reducing the many uncertainties surrounding new investigational treatments that arise when trials are stopped prematurely. (shrink)

Civil society organizations (CSOs) have significantly impacted on the politics of health research and the field of bioethics. In the globalHIVepidemic,CSOs have served a pivotal stakeholder role. The dire need for development of new prevention technologies has raised critical challenges for the ethical engagement of community stakeholders inHIVresearch. This study explored the perspectives ofCSOrepresentatives involved inHIVprevention trials (HPTs) on the impact of premature trial closures on stakeholder engagement. Fourteen respondents fromSouthAfrican and internationalCSOs representing activist and advocacy groups, community mobilisation (...) initiatives, and human and legal rights groups were purposively sampled based on involvement inHPTs. Interviews were conducted fromFebruary‐May 2010. Descriptive analysis was undertaken across interviews and key themes were developed inductively.CSOrepresentatives largely described positive outcomes of recent microbicide andHIVvaccine trial terminations, particularly inSouthAfrica, which they attributed to improvements in stakeholder engagement. Ongoing challenges to community engagement included the need for principled justifications for selective stakeholder engagement at strategic time‐points, as well as the need for legitimate alternatives toCABs as mechanisms for engagement. Key issues forCSOs in relation to research were also raised. (shrink)

During an illness requiring brief use of life-sustaining therapy, patients and surrogates sometimes feel that LST must be withdrawn before it becomes unnecessary to avoid later being stuck living in a debilitated condition that the patient considers worse than death. This fear depends on the belief that the patient can legitimately refuse only artificial LST, so that if such therapies are no longer required, he or she will have missed the ‘opportunity to die.’ This fear of being stuck with life (...) can lead to premature decisions to terminate LST and is unfounded because adequate ethical and moral justification exists for refusal of not just artificial LST, but also for refusal of natural LST, including oral hydration and nutrition. (shrink)

Research teams have used extra-uterine systems to support premature fetal lambs and to bring them to maturation in a way not previously possible. The researchers have called attention to possible implications of these systems for sustaining premature human fetuses in a similar way. Some commentators have pointed out that perfecting these systems for human fetuses might alter a standard expectation in abortion practices: that the termination of a pregnancy also entails the death of the fetus. With Biobags, (...) it might be possible, some argue, that no woman has the right to expect that outcome if the technology is able to sustain fetal lifeafteran abortion. In order to protect the expectation that the termination of a pregnancy always entails the death of the fetus, Elizabeth Romanis has argued that fetuses sustained in Biobags have a status different than otherwise ‘born’ children. In support of that view, she argues that these ‘gestatelings’ are incapable of independent life. This argument involves a misunderstanding of the gestational support involved, as well as a misapprehension of neonatology practice. Here, we argue that any human fetus sustained in a Biobag would be as ‘independent’ as any other premature infant, and just as ‘born’. Neonatologists would seem to have certain presumptive moral responsibilities toward any human fetus gestating in a Biobag. It remains a separate question whether the perfection and widespread application of Biobags for premature human beings would or should alter the expectation that ending a pregnancy also entails fetal death. (shrink)

Research teams have used extra-uterine systems to support premature fetal lambs and to bring them to maturation in a way not previously possible. The researchers have called attention to possible implications of these systems for sustaining premature human fetuses in a similar way. Some commentators have pointed out that perfecting these systems for human fetuses might alter a standard expectation in abortion practices: that the termination of a pregnancy also entails the death of the fetus. With Biobags, (...) it might be possible, some argue, that no woman has the right to expect that outcome if the technology is able to sustain fetal life _after_ an abortion. In order to protect the expectation that the termination of a pregnancy always entails the death of the fetus, Elizabeth Romanis has argued that fetuses sustained in Biobags have a status different than otherwise ‘born’ children. In support of that view, she argues that these ‘gestatelings’ are incapable of independent life. This argument involves a misunderstanding of the gestational support involved, as well as a misapprehension of neonatology practice. Here, we argue that any human fetus sustained in a Biobag would be as ‘independent’ as any other premature infant, and just as ‘born’. Neonatologists would seem to have certain presumptive moral responsibilities toward any human fetus gestating in a Biobag. It remains a separate question whether the perfection and widespread application of Biobags for premature human beings would or should alter the expectation that ending a pregnancy also entails fetal death. (shrink)

A number of developments in the medical field have changed the debate about the ethics of abortion. These developments include: advances in fetal physiology, the increase in neonatal intensive care and the survival rates of premature infants. This paper discusses the idea of selective termination and the effects that these decisions have on disabled people of today. It presents a critique of the counselling services that are provided for the parents of a disabled fetus and discusses how this (...) is viewed from a social perspective. The article ends with an argument that the mother deserves to be autonomous in the decision of abortion. The easiest and most fair way to develop her autonomy is to consider the relationship between a professional and a mother as an expert–expert relationship. Here both parties are considered experts in diagnostic information, treatment options, possibilities, and their history, family roots, philosophy and way of life, respectively. (shrink)

During the last two decades there has been an enormous development in treatment possibilities in the field of neonatology, particularly for (extremely) premature infants. Although there are cross-cultural differences in treatment strategy, an overview of the literature suggests that every country is confronted with moral dilemmas in this area. These concern decisions to initiate or withhold treatment directly at birth and, later on, decisions to withdraw treatment with the possible consequence that the child will die. Given that the neonate (...) cannot express his or her own will, who will decide? And on the basis of what information, values and norms? We explored some of these issues in daily practice by interviewing a small sample of health care practitioners in a Dutch university Neonatal Intensive Care Unit (NICU). It turned out that experiencing moral dilemmas is part of their daily functioning. Nurses underline the suffering of the newborn, whereas physicians stress uncertainty in treatment outcome. To make the best of it, nurses focus on their caring task, whereas physicians hope that future follow-up research will lead to more predictable outcomes. As for their own offspring, part of these professionals would hesitate to bring their own extremely premature newborn to a NICU. For the most oppressing dilemma reported – terminating an already initiated treatment – we propose the concept of ‘evidence shift’ to clarify the ambiguous position of uncertainty in decision making. (shrink)

Two incompatible policies exist for guiding medical decisions for extremely premature, sick, or terminally ill infants, the Best Interests Standard and the newer, 20-year old "Baby Doe" Rules. The background, including why there were two sets of Baby Doe Rules, and their differences with the Best Interests Standard, are illustrated. Two defenses of the Baby Doe Rules are considered and rejected. The first, held by Reagan, Koop, and others, is a "right-to-life" defense. The second, held by some leaders of (...) the American Academy of Pediatrics, is that the Baby Doe Rules are benign and misunderstood. The Baby Doe Rules should be rejected since they can thwart compassionate and individualized decision-making, undercut duties to minimize unnecessary suffering, and single out one group for treatment adults would not want for themselves. In these ways, they are inferior to the older Best Interests Standard. A "negative" analysis of the Best Interests Standard is articulated and defended for decision-making for all incompetent individuals. (shrink)

In recent months, Covid‐19 has devastated African American communities across the nation, and a Minneapolis police officer murdered George Floyd. The agents of death may be novel, but the phenomena of long‐standing epidemics of premature black death and of police violence are not. This essay argues that racial health and health care disparities, rooted as they are in systemic injustice, ought to carry far more weight in clinical ethics than they generally do. In particular, this essay examines palliative and (...) end‐of‐life care for African Americans, highlighting the ways in which American medicine, like American society, has breached trust. In the experience of many African American patients struggling against terminal illness, health care providers have denied them a say in their own medical decision‐making. In the midst of the Covid‐19 pandemic, African Americans have once again been denied a say with regard to the rationing of scarce medical resources such as ventilators, in that dominant and ostensibly race‐neutral algorithms sacrifice black lives. Is there such thing as a “good” or “dignified” death when African Americans are dying not merely of Covid‐19 but of structural racism? (shrink)

Civil society organizations (CSOs) have significantly impacted on the politics of health research and the field of bioethics. In the global HIV epidemic, CSOs have served a pivotal stakeholder role. The dire need for development of new prevention technologies has raised critical challenges for the ethical engagement of community stakeholders in HIV research. This study explored the perspectives of CSO representatives involved in HIV prevention trials (HPTs) on the impact of premature trial closures on stakeholder engagement. Fourteen respondents from (...) South African and international CSOs representing activist and advocacy groups, community mobilisation initiatives, and human and legal rights groups were purposively sampled based on involvement in HPTs. Interviews were conducted from February-May 2010. Descriptive analysis was undertaken across interviews and key themes were developed inductively. CSO representatives largely described positive outcomes of recent microbicide and HIV vaccine trial terminations, particularly in South Africa, which they attributed to improvements in stakeholder engagement. Ongoing challenges to community engagement included the need for principled justifications for selective stakeholder engagement at strategic time-points, as well as the need for legitimate alternatives to CABs as mechanisms for engagement. Key issues for CSOs in relation to research were also raised. (shrink)

During an illness requiring brief use of life-sustaining therapy, patients and surrogates sometimes feel that LST must be withdrawn before it becomes unnecessary to avoid later being stuck living in a debilitated condition that the patient considers worse than death. This fear depends on the belief that the patient can legitimately refuse only artificial LST, so that if such therapies are no longer required, he or she will have missed the ‘opportunity to die.’ This fear of being stuck with life (...) can lead to premature decisions to terminate LST and is unfounded because adequate ethical and moral justification exists for refusal of not just artificial LST, but also for refusal of natural LST, including oral hydration and nutrition. (shrink)

With breathtalung speed, traditional criminal prohibitions against assisted suicide have been declared unconstitutional in twelve states, including California and New York. This poses great promise and great peril. The promise is that competent terminally ill patients, as a compassionate measure of last resort, will have the option of putting an end to their suffering by physician-assisted suicide. More sigmficant, legally permitting this controversial option may be a catalyst for doctors, health care institutions, and society to improve the care of the (...) dying. PAS should be limited only to those relatively few competent patients who continue to suffer intolerably despite unrestrained efforts to palliate and who face a continued existence that they regard as worse than death. When dying patients know they will not be abandoned to miserable and pointless suffering if palliative care fails, they will be fortified to cope better with the process of dying.The immediate peril is that PAS will become a quick fix, available on demand to any patient diagnosed as terminally ill, thus bypassing palliative care and producing premature deaths. (shrink)

Ong, Caroline In February 2014, the Belgian parliament passed an amendment to the Belgian Act on Euthanasia of May 28th, 2002 removing the age limit of those requesting euthanasia provided that they have discerning capabilities and their parents approve. After mentioning briefly the arguments against legalising euthanasia, this article questions the ethical validity of removing the age limit, as well as the presumption that ending lives prematurely allows people to die with dignity. Caring for people who are vulnerable in their (...) suffering is the proper goal of the healing professions, not terminating lives. (shrink)