Spheres of Morality: The Ethical Codes of the Medical Profession.

The medical profession contains five "spheres of morality": clinical care, clinical research, scientific knowledge, population health, and the market. These distinct sets of normative commitments require physicians to act in different ways depending on the ends of the activity in question. For example, a physician-scientist emphasizes patients' well-being in clinic, prioritizes the scientific method in lab, and seeks to maximize shareholder returns as a board member of a pharmaceutical firm. Physicians increasingly occupy multiple roles in healthcare and move between them frequently, creating the possibility of conflict between the ethical obligations of their various roles. This paper examines the entire moral landscape of medicine through the lens of role morality. It develops a novel framework that helps physicians recognize how their moral commitments depend on the nature and context of the situation, clarifies ethical conflicts that physicians face, and concludes with ideas for resolving these conflicts.

Evaluating the Ability to Consent to Research: A Twenty-Year Track Record.

Occasionally, the ability of prospective research participants to consent may be uncertain. Yet standardized capacity-assessment tools may not suffice to determine the ability to consent to a particular research protocol. This study consisted of a retrospective review of the outcomes of an alternative approach used by the Ability to Consent Assessment Team at the National Institutes of Health. Of 944 individuals evaluated over 20 years (1999-2019), 70.1% were determined to have capacity to consent to participate in research. Of those who lacked capacity to consent and were subsequently evaluated for their ability to assign a surrogate, 86.0% had the ability to do so. The findings demonstrate that establishing a task-specific approach for assessing the capacity of potential participants to consent to a variety of research protocols can facilitate safe and ethically justifiable inclusion of individuals whose ability to consent is initially uncertain.

Capacity Evaluations of Psychiatric Patients Requesting Assisted Death in the Netherlands.

BACKGROUND: Euthanasia or physician-assisted suicide (EAS) of psychiatric patients is legal in some countries but remains controversial. OBJECTIVE: This study examined a frequently raised concern about the practice: how physicians address the issue of decision-making capacity of persons requesting psychiatric EAS. METHODS: A review of psychiatric EAS case summaries published by the Dutch Regional Euthanasia Review Committees. Directed content analysis using a capacity-specific 4 abilities model (understanding of facts, applying those facts to self, weighing/reasoning, and evidencing choice) was used to code texts discussing capacity. A total of 66 cases from 2011-2014 were reviewed. RESULTS: In 55% (36 of 66) of cases, the capacity-specific discussion consisted of only global judgments of patients' capacity, even in patients with psychotic disorders. Further, 32% (21 of 66) of cases included evidentiary statements regarding capacity-specific abilities; only 5 cases (8%) mentioned all 4 abilities. Physicians frequently stated that psychosis or depression did or did not affect capacity but provided little explanation regarding their judgments. Physicians in 8 cases (12%) disagreed about capacity; even when no explanation was given for the disagreement, the review committees generally accepted the judgment of the physician performing EAS. In one case, the physicians noted that not all capacity-specific abilities were intact but deemed the patient capable. CONCLUSION: Case summaries of psychiatric EAS in the Netherlands do not show that a high threshold of capacity is required for granting EAS. Although this may reflect limitations in documentation, it likely represents a practice that reflects the normative position of the review committees.

FBXO11 promotes ubiquitination of the Snail family of transcription factors in cancer progression and epidermal development.

The Snail family of transcription factors are core inducers of epithelial-to-mesenchymal transition (EMT). Here we show that the F-box protein FBXO11 recognizes and promotes ubiquitin-mediated degradation of multiple Snail family members including Scratch. The association between FBXO11 and Snai1 in vitro is independent of Snai1 phosphorylation. Overexpression of FBXO11 in mesenchymal cells reduces Snail protein abundance and cellular invasiveness. Conversely, depletion of endogenous FBXO11 in epithelial cancer cells causes Snail protein accumulation, EMT, and tumor invasion, as well as loss of estrogen receptor expression in breast cancer cells. Expression of FBXO11 is downregulated by EMT-inducing signals TGFß and nickel. In human cancer, high FBXO11 levels correlate with expression of epithelial markers and favorable prognosis. The results suggest that FBXO11 sustains the epithelial state and inhibits cancer progression. Inactivation of FBXO11 in mice leads to neonatal lethality, epidermal thickening, and increased Snail protein levels in epidermis, validating that FBXO11 is a physiological ubiquitin ligase of Snail. Moreover, in C. elegans, the FBXO11 mutant phenotype is attributed to the Snail factors as it is suppressed by inactivation/depletion of Snail homologs. Collectively, these findings suggest that the FBXO11-Snail regulatory axis is evolutionarily conserved and critically governs carcinoma progression and mammalian epidermal development.