It is well established that microRNAs (miRNAs) induce mRNA degradation by binding to 3′ untranslated regions (UTRs). The functionality of sites in the coding domain sequence (CDS), on the other hand, remains under discussion. Such sites have limited impact on target mRNA abundance and recent work suggests that miRNAs bind in the CDS to inhibit translation. What then could be the regulatory benefits of translation inhibition through CDS targeting compared to mRNA degradation following 3′ UTR binding? We propose that these (...) domain‐dependent effects serve to diversify the functional repertoire of post‐transcriptional gene expression control. Possible regulatory benefits may include tuning the time‐scale and magnitude of post‐transcriptional regulation, regulating protein abundance depending on or independently of the cellular state, and regulation of the protein abundance of alternative splice variants. Finally, we review emerging evidence that these ideas may generalize to RNA‐binding proteins beyond miRNAs and Argonaute proteins. (shrink)

One of the major issues in the debate about the future of health care is how to keep costs under control while meeting growing demands for care. Addressing that, especially on an international scale, is far from easy. How are we to determine what the demands for care will most likely be? Even if it is not possible to estimate the future number of dependent elderly persons with any precision, it is hard to ignore the most probable scenario: a substantial (...) increase in the number of the oldest old. (shrink)

Social fears emerging in adolescence can have negative effects on emotional well-being. Yet the mechanisms by which these risks occur are unknown. One possibility is that associative learning results in fears to previously neutral social stimuli. Such conditioned responses may alter subsequent processing of social stimuli. We used a novel conditioning task to examine how associative processes influence social fear and attention orienting in adolescents. Neutral photographs were paired with socially rewarding or aversive stimuli during conditioning; a dot-probe task then (...) assessed biases in attention orienting. The social conditioning task modified subjective ratings of the neutral stimuli. Moreover, for the neutral stimulus that was paired with the aversive stimulus, the strength of conditioning showed a relationship with subsequent attentional vigilance. The findings elucidate mechanisms by which negative peer experiences during adolescence may affect emotional processing. (shrink)

In the past, biblical scholarship has neglected the hermeneutical contribution that an imaginal engagement with the text may make. The author’s aim in this article was to develop theological imagination as a hermeneutical device. This was done by briefly considering the concurrence in the hermeneutic contributions of three interpreters of biblical texts, with specific regard to their understanding of biblical imagination. These were Walter Brueggemann, Paul Ricoeur and Ignatius of Loyola. Their hermeneutical contributions concur in their understanding of a biblically (...) informed imagination, and it is specifically this aspect of the concurrence of their thought that was explored. An illustration from Proverbs 14:27, which draws on the metaphor and biblical motif of the fountain or source of life, was put forward to demonstrate how the concurrence in the contributions of these biblical interpreters may influence an imaginal engagement with the text.Keywords: Old Testament; Proverbs; Hermeneutics; The fear of the Lord/Yahweh; Walter Brueggemann; Paul Ricoeur; Ignatius of Loyola; Imaginal engagement. (shrink)

A Ricoeurian hermeneutic affords readers of the Old Testament an opportunity to access the biblical text anew as a source and norm for faith. Reese gave a convenient summarising description of Ricoeur’s hermeneutical approach. Ricoeur organised his considerations around four poles, namely distanciation, objectification, projecting of a world, and appropriation. These operate as the structuring considerations of a Ricoeurian hermeneutic and were illustrated with a sample proverb from the collection Proverbs 10:1–15:33.

Should Proverbs be read as prose or poetry? Considering the language craft is of essential significance for a hermeneutical enquiry into the biblical book of Proverbs. Five suppositions to support the presupposition that Proverbs is best read as poetry were considered.

The UK Genethics Club was established in November 2001 in order to provide a national forum of ethics support for the profession of clinical genetics in the UK. The forum brings together health professionals, medical ethicists and lawyers and support is provided through detailed discussion of cases and sharing of good practice. Clinical genetics professionals had previously voiced concerns about making extremely difficult ethical decisions, with profound implications, in something of a vacuum. Professionals saw a lack of guidance in the (...) area and lack of time for discussion of difficult cases as reasons for this. This paper describes the origins of the group and gives (anonymized) examples of some of the types of issues discussed. (shrink)

There is a paucity of experimental data addressing how peers influence adolescent risk-taking. Here, we examined peer effects on risky decision-making in adults and adolescents using a virtual social context that enabled experimental control over the peer “interactions”. 40 adolescents (age 11-18) and 28 adults (age 20-38) completed a risk-taking (Wheel of Fortune) task under 4 conditions: in private; while being observed by (fictitious) peers; and after receiving ‘risky’ or ‘safe’ advice from the peers. For high-risk gambles (but not medium-risk (...) or even gambles), adolescents made more risky decisions under peer observation than adults. Adolescents, but not adults, tended to resist ‘safe’ advice for high-risk gambles. Although both groups tended to follow ‘risky’ advice for high-risk gambles, adults did so more than adolescents. These findings highlight the importance of distinguishing between the effects of peer observation and peer advice on risky decision-making. (shrink)

We thank Parker and Wright for engaging in this roundtable debate in such a spirited way. The ‘Pharmacogenetic [test] to Avoid Loss of Hearing’ (PALOH) Trial is the first time a genetic point of care test has been applied in the acute neonatal setting; therefore, it is not surprising that questions have been raised which require debate, discussion and clarification. Parker and Wright misattribute several assumptions to the roundtable authors, which we would like to clarify here. Since they raise wider (...) questions about the PALOH trial itself, several of the roundtable discussants have made a joint response. (shrink)

Our ability to generate genomic data is currently well ahead of our ability to understand what they mean, raising challenges about how best to engage with them. This article considers ethical aspects of work with such data, focussing on research contexts that are intertwined with clinical care. We discuss the identifying nature of genomic data, the medical information intrinsic within them, and their linking of people within a biological family. We go on to consider what this means for consent, the (...) importance of thoughtful sharing of genomic data, the challenge of constructing meaningful findings, and the legacy of unequal representation in genomic datasets. We argue that the ongoing success of genomic data research relies on public trust in the enterprise: to justify this trust, we need to ensure robust stewarding, and wide engagement about the ethical issues inherent in such practices. (shrink)

Considerations of the notion of preparedness have come to the fore in the recent pandemic, highlighting a need to be better prepared to deal with sudden, unexpected and unwanted events. However, the concept of preparedness is also important in relation to planned for and desired interventions resulting from healthcare innovations. We describe ethical preparedness as a necessary component for the successful delivery of novel healthcare innovations, and use recent advances in genomic healthcare as an example. We suggest that practitioners and (...) organisations charged with delivering innovative and ambitious healthcare programmes can only succeed if they are able to exhibit the attribute of ethical preparedness. (shrink)

This study investigates the persuasiveness of different types of expert evidence. Following Wagemans, two types of experts were distinguished that can be used in expert evidence: experiential experts and professional experts. In a between-subjects experiment, these different types of experts were included in a news report on a political issue. Results indicate that the perceived expertise and persuasiveness of professional experts was higher than that of experiential experts. Perceived expertise completely mediated the effects of the different types of expert evidence (...) on persuasion. These results point towards a recommendation of using professional expert evidence over experiential expert evidence in reporting on political issues. (shrink)

Sight is undoubtedly the most crucial sense, and accidents resulting in its loss are a significant tragedy for individuals. The scientific community embarked on a journey of scientific innovation i...

In this round table response, we discuss some of the problems inherent in insisting on specific consent for an activity that needs to happen rapidly as part of a package of care. The Human Tissue Authority (the UK regulator for human tissue and organs) consider that specific consent is mandatory to assess which antibiotics are appropriate on the neonatal unit, but this insistence may actually limit the autonomy which consent aims to promote. While genetic testing to determine which child will (...) react adversely to particular antibiotics has been available clinically for several years, the research proposed here is to assess whether improving the speed of testing allows decisions to be made before treatment starts. Insisting on specific consent before this activity can take place is likely to delay appropriate care in some cases. On admission to the neonatal unit, the unwell infant is routinely subjected to a range of investigations and treatments. A person with parental responsibility will usually be asked to provide consent to undertake treatments for children who do not have capacity to give consent themselves.1 For the acutely unwell child, consent will usually be sought for a package of care: the urgent nature of neonatal medicine often requires clinicians to make many decisions without explicit consent. Doctors must always act in a child’s best interests: their decisions need to protect the health and well-being of a child and hold the child’s welfare paramount in accordance with the Children Act (1989) and General Medical Council (GMC) guidelines.1 2 Thus, for example, ventilation might be initiated, sedation provided, antibiotics commenced or diagnostic investigations requested without separate consent conversations or …. (shrink)

Gyngell and colleagues consider that the recent Nuffield Council report does not go far enough: heritable genome editing is not just justifiable in a few rare cases; instead, there is a moral imperative to undertake it. We agree that there is a moral argument for this, but in the real world it is mitigated by the fact that it is not usually possible to ensure a better life. We suggest that a moral imperative for HGE can currently only be concluded (...) if one first buys into an overly deterministic view of a genome sequence, and the role of variation within in it, in the aetiology of the disease: most diseases cannot simply be attributed to specific genetic variants that we could edit away. Multiple, poorly understood genetic and environmental factors interact to influence the expression of diseases with a genetic component, even well understood ‘monogenic’ disorders. Population-level genome analyses are now demonstrating that many genetic ’mutations' are much less predictive than previously thought 1. Furthermore, HGE might introduce new risks just as it reduces old ones; or remove protections not yet clearly delineated. (shrink)

This article extends the definition of sensationalism to print media by arguing that language intensifiers may be an aspect of sensationalism. In addition, this paper investigates if an indirect effect can be established by which sensationalistic message features influence news reception through the perception of sensationalism. Two between-subjects experiments show that sensationalistic message features like intensifiers increase perceived language intensity. In experiment 1, intensifiers had a negative effect on news article appreciation, which was not influenced by PLI. Experiment 2 revealed (...) positive indirect effects of intensifiers through PLI on newsworthiness and news article appreciation. (shrink)

Previous studies have shown that identification and self-referencing can both function as mechanisms of narrative persuasion. However, it is not yet clear whether they are compatible and can work together in bringing about persuasive effects of narratives, or not. Therefore, this study examines both identification and self-referencing and studies their relation and effects. A 2x2 between-subjects experiment was conducted among 185 student participants, with the factors ‘perspective’ (1st vs. 3rd person) to influence identification and ‘similarity’ (young student protagonist vs. older (...) working protagonist) to influence self-referencing. Results showed that identification mediated indirect effects of perspective on story-consistent belief and self-referencing mediated indirect effects of similarity on story-consistent belief. Moreover, identification and self-referencing serially mediated indirect effects on story-consistent belief. These results indicate that identification and self-referencing are compatible processes which can work together as mechanisms of narrative persuasion. (shrink)

Centralised, compliance-focused approaches to research ethics have been normalised in practice. In this paper, we argue that the dominance of such systems has been driven by neoliberal approaches to governance, where the focus on controlling and individualising risk has led to an overemphasis of decontextualised ethical principles and the conflation of ethical requirements with the documentation of ‘informed consent’. Using a UK-based case study, involving a point-of-care-genetic test as an illustration, we argue that rather than ensuring ethical practice such compliance-focused (...) approaches may obstruct valuable research. We call for an approach that encourages researchers and research communities—including regulators, ethics committees, funders and publishers of academic research—to acquire skills to make morally appropriate decisions, and not base decision-making solely on compliance with prescriptive regulations. We call this ‘ethical preparedness’ and outline how a research ethics system might make space for this approach. (shrink)

This paper proposes a refocusing of consent for clinical genetic testing, moving away from an emphasis on autonomy and information provision, towards an emphasis on the virtues of healthcare professionals seeking consent, and the relationships they construct with their patients. We draw on focus groups with UK healthcare professionals working in the field of clinical genetics, as well as in-depth interviews with patients who have sought genetic testing in the UK’s National Health Service. We explore two aspects of consent: first, (...) how healthcare professionals consider the act of ‘consenting’ patients; and second how these professional accounts, along with the accounts of patients, deepen our understanding of the consent process. Our findings suggest that while healthcare professionals working in genetic medicine put much effort into ensuring patients’ understanding about their impending genetic test, they acknowledge, and we show, that patients can still leave genetic consultations relatively uninformed. Moreover, we show how placing emphasis on the informational aspect of genetic testing is not always reflective of, or valuable to, patients’ decision-making. Rather, decision-making is socially contextualised – also based on factors outside of information provision. A more collaborative on-going consent process, grounded in virtue ethics and values of honesty, openness and trustworthiness, is proposed. (shrink)

Much has been published about the ethical issues encountered by clinicians in genetics/genomics, but those experienced by clinical laboratory scientists are less well described. Clinical laboratory scientists now frequently face navigating ethical problems in their work, but how they should be best supported to do this is underexplored. This lack of attention is also reflected in the ethics tools available to clinical laboratory scientists such as guidance and deliberative ethics forums, developed primarily to manage issues arising within the clinic.We explore (...) what ethical issues are being experienced by clinical scientists, how they think such issues could be best analysed and managed, and whether their practice might be enhanced by more situated approaches to ethics deliberation and practice such as ethical preparedness. From thematic analysis of cases presented by clinical scientists at a specially convened meeting of the UK Genethics Forum, we derived three main ethical themes: (1) the redistribution of labour and responsibilities resulting from the practice of genomic medicine; (2) the interpretation and certainty of results and (3) the proposal that better standardisation and consistency of ethical approaches (for example, more guidelines and policy) could resolve some of the challenges arising.We argue that although standardisation is important for promoting shared understandings of good (including ethical) practice, supplementary approaches to enhance and sustain ethical preparedness will be important to help clinical scientists and others in the recently expanded genetic/genomic medicine environment foster quality ethical thinking. (shrink)

We discuss a case where clinical genomic investigation of muscle weakness unexpectedly found a genetic variant that might (or might not) predispose to kidney cancer. We argue that despite its off-target and uncertain nature, this variant should be discussed with the man who had the test, not because it is medical information, but because this discussion would allow the further clinical evaluation that might lead it to becoming so. We argue that while prominent ethical debates around genomics often take ‘results’ (...) as a starting point and ask questions as to whether to look for and how to react to them, the construction of genomic results is fraught with ethical complexity, although often couched as a primarily technical problem. We highlight the need for greater focus on, and appreciation of, the ethical work undertaken daily by scientists and clinicians working in genomic medicine and discuss how public conversations around genomics need to adapt to prepare future patients for potentially uncertain and unexpected outcomes from clinical genomic tests. (shrink)

We thank Lucy Frith for her thought-provoking response1 to our paper, where we argued that it would be ethically acceptable to contact an anonymous egg donor to help facilitate diagnostic genetic testing for a donor-conceived child.2 While we read Frith’s commentary with interest, we still think that the egg donor should be contacted in the case that we describe. Frith raises concerns as to whether contact would constitute ‘ overriding consent ’, thus ’ potentially set(ting) a dangerous precedent ’ for (...) existing gamete donors and donor-conceived children. In contrast, we consider that contacting the egg donor would not override her consent, as her views on contact in the instance that has now arisen were never sought. Our view is that given we do not currently know what she might want, contacting her is a more legitimate way of respecting her autonomy than trying to anticipate her likely answer. We strongly agree with Frith’s suggestion that future consent discussions around gamete donation should make explicit ‘ the possibility of being contacted in the future if there is a relevant reason for doing so ’. Frith expresses a concern that contact would constitute ‘ overriding [the egg donor’s] consent ’, meaning that we have to ‘ justify contacting the egg donor against her previously stated wishes not to be contacted ’. However, our argument is that the egg donor was never asked whether or not she was happy to be contacted in the circumstances that have now arisen. Thus, there is no consent to be overridden, given that she never gave or withheld it in the first place. Frith rightly acknowledges that her arguments therefore ‘ [do] not fully address [our] main worry that the donor’s wishes are essentially unknown, as she was not asked about this specific situation and …. (shrink)

Involving patients in decisions on primary prevention can be questioned from an ethical perspective, due to a tension between health promotion activities and patient autonomy. A nurse-led intervention for prevention of cardiovascular diseases, including counselling (risk communication, and elements of shared decision-making and motivational interviewing) and supportive tools such as a decision aid, was implemented in primary care. The aim of this study was to evaluate the nurse-led intervention from an ethical perspective by exploring in detail the experiences of patients (...) with the intervention, and their views on the role of both the nurse and patient. The study had a qualitative design. 18 patients who had received the intervention participated. Data were gathered by in-depth interviews. The interviews were analysed using directed content analysis. The findings revealed that patients perceived the consultations not as an infringement on their autonomy, but as supportive to risk reduction efforts they tried but found hard to realise. They specifically emphasised the role of the nurse, and appreciated the nurse's realistic advice, encouragement, and help in understanding. Patients' views on and experiences with risk management are in line with notions of relational autonomy, caring cooperation and communicative action found in the literature. We conclude that patients define the relationship with the nurse as shared work in the process of developing a healthier lifestyle. (shrink)

El surgimiento de nuevas terapias ha generado un debate sobre sus implicaciones éticas, médicas y sociales. En este contexto, el personalismo ontológico se ha convertido en una corriente importante de la bioética, el cual está centrado en salvaguardar la dignidad humana y potenciar el bien integral de las personas. Sus principios orientadores son la defensa de la vida física, la justificación de toda intervención terapéutica, la exigencia del principio del consentimiento y la consideración de implicaciones sociales y de justicia en (...) la asignación de recursos. El presente estudio se llevó a cabo para conocer la influencia de estos principios en el ejercicio profesional del personal de salud que trabaja en trasplantes. Se aplicó, de forma presencial y en línea, una guía de valoración ética de intervenciones sobre el cuerpo humano, adaptada con los principios de la bioética personalista. Participaron siete expertos (57 % hombres; media de 46 años) y con los resultados se hizo un análisis de contenido y de la frecuencia de los datos. Como resultado, se destaca que el trasplante de cara puede mejorar la calidad de vida del receptor, pero se encuentra limitado por el costo económico y se reporta que el trasplante de cara cumple con los principios de defensa de la vida humana física, terapéuticos, de libertad y responsabilidad, y de sociabilidad y subsidiariedad. Finalmente, se concluye que el trasplante facial es una técnica óptima y necesaria para el progreso de la medicina y que la evaluación ética es fundamental para armonizar con los avances científicos y tecnológicos. (shrink)