Living bioethics, theories and children's consent to heart surgery.

Background: This analysis is about practical living bioethics and how law, ethics and sociology understand and respect children's consent to, or refusal of, elective heart surgery. Analysis of underlying theories and influences will contrast legalistic bioethics with living bioethics. In-depth philosophical analysis compares social science traditions of positivism, interpretivism, critical theory and functionalism and applies them to bioethics and childhood, to examine how living bioethics may be encouraged or discouraged. Illustrative examples are drawn from research interviews and observations in two London paediatric cardiac units. This paper is one of a series on how the multidisciplinary cardiac team members all contribute to the complex mosaic of care when preparing and supporting families' informed consent to surgery. Results: The living bioethics of justice, care and respect for children and their consent depends on theories and practices, contexts and relationships. These can all be undermined by unseen influences: the history of adult-centric ethics; developmental psychology theories; legal and financial pressures that require consent to be defined as an adult contract; management systems and daily routines in healthcare that can intimidate families and staff; social inequalities. Mainstream theories in the clinical ethics literature markedly differ from the living bioethics in clinical practices. Conclusion: We aim to contribute to raising standards of respectful paediatric bioethics and to showing the relevance of virtue and feminist ethics, childhood studies and children's rights.

Complexes of vertebrate TMC1/2 and CIB2/3 proteins form hair-cell mechanotransduction cation channels.

Calcium and integrin-binding protein 2 (CIB2) and CIB3 bind to transmembrane channel-like 1 (TMC1) and TMC2, the pore-forming subunits of the inner-ear mechanoelectrical transduction (MET) apparatus. Whether these interactions are functionally relevant across mechanosensory organs and vertebrate species is unclear. Here we show that both CIB2 and CIB3 can form heteromeric complexes with TMC1 and TMC2 and are integral for MET function in mouse cochlea and vestibular end organs as well as in zebrafish inner ear and lateral line. Our AlphaFold 2 models suggest that vertebrate CIB proteins can simultaneously interact with at least two cytoplasmic domains of TMC1 and TMC2 as validated using nuclear magnetic resonance spectroscopy of TMC1 fragments interacting with CIB2 and CIB3. Molecular dynamics simulations of TMC1/2 complexes with CIB2/3 predict that TMCs are structurally stabilized by CIB proteins to form cation channels. Overall, our work demonstrates that intact CIB2/3 and TMC1/2 complexes are integral to hair-cell MET function in vertebrate mechanosensory epithelia.

Living bioethics, clinical ethics committees and children's consent to heart surgery.

This discussion paper considers how seldom recognised theories influence clinical ethics committees. A companion paper examined four major theories in social science: positivism, interpretivism, critical theory and functionalism, which can encourage legalistic ethics theories or practical living bioethics, which aims for theory-practice congruence. This paper develops the legalistic or living bioethics themes by relating the four theories to clinical ethics committee members' reported aims and practices and approaches towards efficiency, power, intimidation, justice, equality and children's interests and rights. Different approaches to framing ethical questions are also considered. Being aware of the four theories' influence can help when seeking to understand and possibly change clinical ethics committee routines. The paper is not a research report but is informed by a recent study in two London paediatric cardiac units. Forty-five practitioners and related experts were interviewed, including eight members of ethics committees, about the work of informing, preparing and supporting families during the extended process of consent to children's elective heart surgery. The mosaic of multidisciplinary teamwork is reported in a series of papers about each profession, including this one on bioethics and law and clinical ethics committees' influence on clinical practice. The qualitative social research was funded by the British Heart Foundation, in order that more may be known about the perioperative views and needs of all concerned. Questions included how disputes can be avoided, how high ethical standards and respectful cooperation between staff and families can be encouraged, and how minors' consent or refusal may be respected, with the support of clinical ethics committees.

Disclosure of non-recent (historic) childhood sexual abuse: What should researchers do?

Non-recent (historic) childhood sexual abuse is an important issue to research, though often regarded as taboo and frequently met with caution, avoidance or even opposition from research ethics committees. Sensitive research, such as that which asks victim-survivors to recount experiences of abuse or harm, has the propensity to be emotionally challenging for both the participant and the researcher. However, most research suggests that any distress experienced is usually momentary and not of any clinical significance. Moreover, this type of research offers a platform for voices which have often been silenced, and many participants report the cathartic effect of recounting their experiences in a safe, non-judgemental space. With regard to the course of such research, lines of inquiry which ask adult participants to discuss their experiences of childhood sexual abuse may result in a first-time disclosure of that abuse by the victim-survivor to the researcher. Guidance about how researchers should respond to first-time disclosure is lacking. In this article, we discuss our response to one research ethics committee which had suggested that for a qualitative study for which we were seeking ethical approval (investigating experiences of pregnancy and childbirth having previously survived childhood sexual abuse), any disclosure of non-recent (historic) childhood sexual abuse which had not been previously reported would result in the researcher being obliged to report it to relevant authorities. We assess this to be inconsistent with both law and professional guidance in the United Kingdom; and provide information and recommendations for researchers and research ethics committees to consider.

Biochar and compost effects on soil microbial communities and nitrogen induced respiration in turfgrass soils.

We examined the effect of a labile soil amendment, compost, and recalcitrant biochar on soil microbial community structure, diversity, and activity during turfgrass establishment. Two application rates of biochar (B1 at 12.5 t ha-1and B2 at 25 t ha-1), a 5 centimeter (cm) green waste compost treatment (CM) in top soil, a treatment with 12.5 t ha-1 biochar and 5 cm compost (B1+CM), and an unamended control (CK) treatment were prepared and seeded with tall fescue. Overall, results of phospholipid fatty acid analysis (PLFA) profiling and Illumina high-throughput sequencing of 16S rRNA genes amplified from soil DNA revealed significant shifts in microbial community structures in the compost amended soils whereas in biochar amended soils communities were more similar to the control, unamended soil. Similarly, increases in enzymatic rates (6-56%) and nitrogen-induced respiration (94%) were all largest in compost amended soils, with biochar amended soils exhibiting similar patterns to the control soils. Both biochar and compost amendments impacted microbial community structures and functions, but compost amendment, whether applied alone or co-applied with biochar, exhibited the strongest shifts in the microbial community metrics examined. Our results suggest application of compost to soils in need of microbiome change (reclamation projects) or biochar when the microbiome is functioning and long-term goals such as carbon sequestration are more desirable.

Mapping protein-polymer conformations in bioconjugates with atomic precision.

Rational design of protein-polymer bioconjugates is hindered by limited experimental data and mechanistic understanding on interactions between the two. In this communication, nuclear magnetic resonance (NMR) paramagnetic relaxation enhancement (PRE) reports on distances between paramagnetic spin labels and NMR active nuclei, informing on the conformation of conjugated polymers. 1H/15N-heteronuclear single quantum coherence (HSQC) NMR spectra were collected for ubiquitin (Ub) modified with block copolymers incorporating spin labels at different positions along their backbone. The resultant PRE data show that the conjugated polymers have conformations biased towards the nonpolar ß-sheet face of Ub, rather than behaving as if in solution. The bioconjugates are stabilized against denaturation by guanidine-hydrochloride, as measured by circular dichroism (CD), and this stabilization is attributed to the interaction between the protein and conjugated polymer.

A Single Salt Bridge in VIM-20 Increases Protein Stability and Antibiotic Resistance under Low-Zinc Conditions.

To understand the evolution of Verona integron-encoded metallo-ß-lactamase (VIM) genes (blaVIM) and their clinical impact, microbiological, biochemical, and structural studies were conducted. Forty-five clinically derived VIM variants engineered in a uniform background and expressed in Escherichia coli afforded increased resistance toward all tested antibiotics; the variants belonging to the VIM-1-like and VIM-4-like families exhibited higher MICs toward five out of six antibiotics than did variants belonging to the widely distributed and clinically important VIM-2-like family. Generally, maximal MIC increases were observed when cephalothin and imipenem were tested. Additionally, MIC determinations under conditions with low zinc availability suggested that some VIM variants are also evolving to overcome zinc deprivation. The most profound increase in resistance was observed in VIM-2-like variants (e.g., VIM-20 H229R) at low zinc availability. Biochemical analyses reveal that VIM-2 and VIM-20 exhibited similar metal binding properties and steady-state kinetic parameters under the conditions tested. Crystal structures of VIM-20 in the reduced and oxidized forms at 1.25 Å and 1.37 Å resolution, respectively, show that Arg229 forms an additional salt bridge with Glu171. Differential scanning fluorimetry of purified proteins and immunoblots of periplasmic extracts revealed that this difference increases thermostability and resistance to proteolytic degradation when zinc availability is low. Therefore, zinc scarcity appears to be a selective pressure driving the evolution of multiple metallo-ß-lactamase families, although compensating mutations use different mechanisms to enhance resistance.IMPORTANCE Antibiotic resistance is a growing clinical threat. One of the most serious areas of concern is the ability of some bacteria to degrade carbapenems, drugs that are often reserved as last-resort antibiotics. Resistance to carbapenems can be conferred by a large group of related enzymes called metallo-ß-lactamases that rely on zinc ions for function and for overall stability. Here, we studied an extensive panel of 45 different metallo-ß-lactamases from a subfamily called VIM to discover what changes are emerging as resistance evolves in clinical settings. Enhanced resistance to some antibiotics was observed. We also found that at least one VIM variant developed a new ability to remain more stable under conditions where zinc availability is limited, and we determined the origin of this stability in atomic detail. These results suggest that zinc scarcity helps drive the evolution of this resistance determinant.

Data Sharing and the Idea of Ownership.

Ideas about ownership are sometimes used in discussions of data sharing in personalised medicine. Personal health data are thought by many to be 'theirs'. Paradoxically, personalised medicine (at least in the context of genomics) relies on the aggregation of private data into a dataset that is held as a form of knowledge commons. When the notions of private and common property that lie behind this discourse are made explicit we can use thinking about the justifications and jurisprudence of property both to clarify the persuasiveness and limits of such claims, and also how they differ from other principles that are at stake in the interplay between individual and collective goods in the delivery of personalised medicine. This shows that ownership might more plausibly lie with health professionals than patients. In a socialised medicine system, such as the NHS, such professionals are agents of the state and ownership would lie with the commons rather than any individual. Common rather than private ownership of genomic information may be more appropriate.

The Virtues of National Ethics Committees.

The United Kingdom has many bodies that play their part in carrying out the work of national ethics committees, but its nearest equivalent of a U.S. presidential bioethics commission is the Nuffield Council on Bioethics, established in 1991. The Council is charged with examining ethical questions raised by developments in biological and medical research, publishing reports, and making representations to appropriate bodies in order to respond to or anticipate public concern. It is a nongovernment organization with no defined or guaranteed channels of influence. It has no authority merely by virtue of the position it holds. Rather, it has established relational authority based on its reputation. Unlike the U.S. bioethics commission, it is not part of executive government, nor is it constituted to contribute to the legislative branch, as does the French Comité Consultatif National d'Ethique. Its nongovernmental status notwithstanding, the Nuffield Council's work affects the U.K. government and the British public, and the Council has achieved international recognition for its reports. I was the chairperson from 2012 to 2017 and draw on my experience in this piece to consider three key audiences: governments, publics, and the international community.

Montgomery on informed consent: an inexpert decision?

Montgomery v Lanarkshire HB is a deeply troubling decision when read closely. Paradoxically, its ruling supporting the principle of autonomy could be justified only by disregarding the individual patient's actual choices and characteristics in favour of a stereotype. The decision demonstrates a lack of expertise in dealing with specific clinical issues and misrepresents professional guidance. More fundamentally, it fails to appreciate the nature of professional expertise. This calls into question the competence of the courts to adjudicate on matters of clinical judgement and makes an attractive formulation of the test for disclosure obligations inherently unpredictable.

Bioethics as a Governance Practice.

Bioethics can be considered as a topic, an academic discipline (or combination of disciplines), a field of study, an enterprise in persuasion. The historical specificity of the forms bioethics takes is significant, and raises questions about some of these approaches. Bioethics can also be considered as a governance practice, with distinctive institutions and structures. The forms this practice takes are also to a degree country specific, as the paper illustrates by drawing on the author's UK experience. However, the UNESCO Universal Declaration on Bioethics can provide a starting point for comparisons provided that this does not exclude sensitivity to the socio-political context. Bioethics governance practices are explained by various legitimating narratives. These include response to scandal, the need to restrain irresponsible science, the accommodation of pluralist views, and the resistance to the relativist idea that all opinions count equally in bioethics. Each approach raises interesting questions and shows that bioethics should be studied as a governance practice as a complement to other approaches.

Research led by participants: a new social contract for a new kind of research.

In recent years, there have been prominent calls for a new social contract that accords a more central role to citizens in health research. Typically, this has been understood as citizens and patients having a greater voice and role within the standard research enterprise. Beyond this, however, it is important that the renegotiated contract specifically addresses the oversight of a new, path-breaking approach to health research: participant-led research. In light of the momentum behind participant-led research and its potential to advance health knowledge by challenging and complementing traditional research, it is vital for all stakeholders to work together in securing the conditions that will enable it to flourish.

Conscientious objection: personal and professional ethics in the public square.

English law expects health professionals to have, and act upon, consciences, but formal conscience clauses are not the main legal recognition of this expectation. Rather, they should be regarded as an anomaly with roots in very specific political settlements between society and health professions, whose legitimacy is historically contingent, and as an aspect of the 'price' to be paid for securing services. There are sound reasons for the protection of conscientious discretion as an aspect of professional identify, but specific rights of personal conscientious objection are difficult to reconcile with legitimate public expectations of comprehensive and non-discriminatory services. Professional identities include moral commitments, such as the privileging of patient safety over administrative convenience. These should not be permitted to be overridden by personal moralities during the course of service delivery (as opposed to debating in the abstract what the proper courses of action should be). Consequently, formal conscientious objection clauses should be reduced to a minimum and regularly revisited. It is generally more satisfactory to address clashes between the personal moralities of professionals and public expectations through more flexible means, enabling accommodation of a plurality of views where possible but acknowledging that this is a matter of striking an appropriate balance. Employment law rather than healthcare law provides the best mechanism for regulating this process.

The compleat lawyer--medical law as practical reasoning: doctrine, empiricism, and engagement.

Margot Brazier has modelled the relationship between legal scholarship and health care practice--an evidence-based approach to doing good in the real world through the application of the discipline of law. No ivory tower academic, but a good citizen. This paper explores the expression of her comprehensive contribution in an academic paper and a policy review. She has shown how law needs to take into account the realities of the clinic when considering the plausibility of various claims for the doctrine of informed consent. She has also demonstrated how discipline could be brought to bear on policy-making, where in the Surrogacy Review she prioritised empirical evidence over preconceptions: evidence-based policy not policy-based evidence as modern consultation documents too often elicit. Margot Brazier has also provided a role model for academic lawyers' contribution to the public good; not only through ensuring the proper administration of the law (as chair of the Animal Procedures Committee for the Home Office), but also in shaping a cathartic response to public concerns as Chair of the Retained Organ Commission. She did not set out to establish a grand theory of medical law, but rather has built an approach that has enriched its practice and has had a lasting impact on those working in the field. In her hands, law is a tool for improving the practice of health care. Efficient practice precedes the theory of it; methodologies presuppose the application of the methods, of the critical investigation of which they are the products. It was because Aristotle found himself and others reasoning now intelligently and now stupidly and it was because Izaak Walton found himself and others angling sometimes effectively and sometimes ineffectively that both were able to give their pupils the maxims and prescriptions of their arts.