Fold‐switching proteins, which remodel their secondary and tertiary structures in response to cellular stimuli, suggest a new view of protein fold space. For decades, experimental evidence has indicated that protein fold space is discrete: dissimilar folds are encoded by dissimilar amino acid sequences. Challenging this assumption, fold‐switching proteins interconnect discrete groups of dissimilar protein folds, making protein fold space fluid. Three recent observations support the concept of fluid fold space: (1) some amino acid sequences interconvert between folds with distinct secondary (...) structures, (2) some naturally occurring sequences have switched folds by stepwise mutation, and (3) fold switching is evolutionarily selected and likely confers advantage. These observations indicate that minor amino acid sequence modifications can transform protein structure and function. Consequently, proteomic structural and functional diversity may be expanded by alternative splicing, small nucleotide polymorphisms, post‐translational modifications, and modified translation rates. (shrink)

Routine infant circumcision is one of the most common surgical procedures performed in the U.S. Despite its broad societal acceptance, the practice is not without controversy. The stories included in this symposium offer rich insight into the diverse set of attitudes, values, and beliefs related to the practice of circumcision. They additionally offer insight into the complex web of personal, interpersonal, and social dynamics that inform the circumcision choices parents make for their children, the reasons parents make them, and how (...) others can influence decisional choices. More broadly, these narratives raise important ethical questions mirrored today in broader contemporary bioethical and public discourse on the scope and limits of parental authority to make decisions for their children, power dynamics in medical decision making, and the ethics of healthcare activism. In this commentary, I discuss three sets of themes related to the ethics of circumcision running through the symposium narratives, comment on the ethical tensions and questions which emerge from each set of themes, gently problematize some of the rhetoric surrounding the ethical permissibility of circumcision, and gesture towards the future of bioethical inquiry on circumcision discourse. (shrink)

This article explores the relationship between gender, technology, language, and how infants and children born with disorders of sexual development are shaped into intelligible members of the community. The contemporary medical model maintains that children ought to be both socially and surgically assigned and reared as one particular gender. Gender scholar Suzanne Kessler rejects this position and argues for the acceptance of greater genital variability through the use of language. Using a Heideggerian lens, the main question I seek to answer (...) in this article is: does Kessler’s approach succeed in its aim to better treat individuals born with disorders of sexual development? I argue that Kessler is successful in offering practical solutions for persons with intersexed conditions to exist and flourish as intelligible members of the community, but that her project ultimately relies on power to “challenge forth” greater acceptance of genital variance. Building on the work of Kessler and Heidegger, I argue that a better approach to making intelligible the existence of an infant born with a disorder of sexual development is not to rely on the manipulation of language, but to instead reinvigorate a sense of the sacred in response to having an intersex condition. (shrink)

The deployment and use of AI systems should be both safe and broadly ethically acceptable. The principles-based ethics assurance argument pattern is one proposal in the AI ethics landscape that seeks to support and achieve that aim. The purpose of this argument pattern or framework is to structure reasoning about, and to communicate and foster confidence in, the ethical acceptability of uses of specific real-world AI systems in complex socio-technical contexts. This paper presents the interim findings of a case study (...) applying this ethics assurance framework to the use of Dora, an AI-based telemedicine system, to assess its viability and usefulness as an approach. The case study process to date has revealed some of the positive ethical impacts of the Dora platform, as well as unexpected insights and areas to prioritise for evaluation, such as risks to the frontline clinician, particularly in respect of clinician autonomy. The ethics assurance argument pattern offers a practical framework not just for identifying issues to be addressed, but also to start to construct solutions in the form of adjustments to the distribution of benefits, risks and constraints on human autonomy that could reduce ethical disparities across affected stakeholders. Though many challenges remain, this research represents a step in the direction towards the development and use of safe and ethically acceptable AI systems and, ideally, a shift towards more comprehensive and inclusive evaluations of AI systems in general. (shrink)

Perception is not an independent, in‐the‐moment event. Instead, perceiving involves integrating prior expectations with current observations. How does this ability develop from infancy through adulthood? We examined how prior visual experience shapes visual perception in infants, children, and adults. Using an identical task across age groups, we exposed participants to pairs of colorful stimuli and implicitly measured their ability to discriminate relative saturation levels. Results showed that adult participants were biased by previously experienced exemplars, and exhibited weakened in‐the‐moment discrimination between (...) different levels of saturation. In contrast, infants and children showed less influence of memory in their perception, and they actually outperformed adults in discriminating between current levels of saturation. Our findings suggest that as humans develop, their perception relies more on prior experience and less on current observation. (shrink)

This volume brings together eminent theologians, philosophers and political theorists to discuss such questions as how religious understandings have shaped the moral landscape of contemporary culture; the possible contributions of theology and theologically informed moral argument to contemporary public life; the problem of religious and moral discourse in a pluralistic society; and the proper relationship between religion and culture.

Objective:Prior research examining sexual and intimacy concerns among metastatic breast cancer patients and their intimate partners is limited. In this qualitative study, we explored MBC patients’ and partners’ experiences of sexual and intimacy-related changes and concerns, coping efforts, and information needs and intervention preferences, with a focus on identifying how the context of MBC shapes these experiences.Methods:We conducted 3 focus groups with partnered patients with MBC [N = 12; M age = 50.2; 92% White; 8% Black] and 6 interviews with (...) intimate partners [M age = 47.3; 83% White; 17% Black]. Participants were recruited through the Fox Chase Cancer Center Tumor Registry and the Cancer Support Community. Qualitative data were analyzed using the Framework Method and Dedoose software.Results:Qualitative analyses revealed several key themes reflecting ways in which MBC shapes experiences of sex/intimacy: the heavy disease/treatment burden leads to significant, long-term sexual concerns and consequent heightened emotional distress for both patients and partners ; viewing the relationship as having “an expiration date” influences patients’ and partners’ concerns related to sex/intimacy and complicates coping efforts; and information needs extend beyond managing sexual side effects to include emotional aspects of intimacy and the added strain of the life-limiting nature of the disease on the relationship. The heightened severity of sexual concerns faced by patients with MBC, compounded by the terminal nature of the disease, may place patients and partners at risk for significant adverse emotional and interpersonal consequences.Conclusion:Findings suggest unique ways in which sex and intimate relationships change after a diagnosis of metastatic breast cancer from both patients’ and partners’ perspectives. Consideration of the substantial physical and emotional burden of MBC and the broader context of the relationship and intimacy overall is important when developing a sexuality-focused intervention in this population. Addressing sexual concerns is a critical part of cancer care with important implications for patients’ health and quality of life. (shrink)

Research Ethics, Volume 18, Issue 1, Page 64-83, January 2022. Automated, wearable cameras can benefit health-related research by capturing accurate and objective information about individuals’ daily experiences. However, wearable cameras present unique privacy- and confidentiality-related risks due to the possibility of the images capturing identifying or sensitive information from participants and third parties. Although best practice guidelines for ethical research with wearable cameras have been published, limited information exists on the risks of studies using wearable cameras. The aim of this (...) literature review was to survey risks related to using wearable cameras, and precautions taken to reduce those risks, as reported in empirical research. Forty-five publications, comprising 36 independent studies, were reviewed, and findings revealed that participants’ primary concerns with using wearable cameras included physical inconvenience and discomfort in certain situations. None of the studies reviewed reported any serious adverse events. Although it is possible that reported findings do not include all risks experienced by participants in research with wearable cameras, our findings suggest a low level of risk to participants. However, it is important that investigators adopt recommended precautions, which can promote autonomy and reduce risks, including participant discomfort. (shrink)

Caretaking stability in the early life environment supports neurobehavioral development, while instability and neglect constitute adverse environments that can alter maturational processes. Research in humans suggests that different types of early life adversity can have differential effects on caretaker relationships and later cognitive and social development; however, identifying mechanistic underpinnings will require animal models with translational validity. Two common rodent models, maternal separation and limited bedding, influence the mother-infant relationship during a critical window of development. We hypothesized that these paradigms (...) may affect the development of communication strategies on the part of the pup. Ultrasonic vocalizations are a care-eliciting mechanism and ethologically relevant response to stressors in the rat pup. USV emission rates and acoustic parameters change throughout early development, presenting the opportunity to define developmental milestones in USVs that would reflect neurobehavioral aberrations if disrupted. This study investigated the effects of MS or LB on the dam-pup relationship by quantifying pup USVs, maternal behavior, and the relationship between the two. First, we used a generalized additive model approach to establish typical developmental trajectories of USV acoustic properties and determine windows of change in MS or LB rearing. Additionally, we quantified maternal behaviors and the predictability of maternal care sequences using an entropy rate calculation. MS and LB each shifted the developmental trajectories of USV acoustic parameters and call types in a sex-specific manner. MS more often impacted male USVs, while LB impacted female USVs. MS dams spent more time passive nursing, and LB dams spent more time on the nest. The predictability of maternal care was associated with the rate of USV emissions exclusively in females. Taken together, findings demonstrate sex- and model-specific effects of rearing environments on a novel developmental trajectory involving the mother-infant relationship, facilitating the translation of animal ELA paradigms to assess later-life consequences. (shrink)

Previous research shows that manipulations (e.g. levels-of-processing) that facilitate true memory often increase susceptibility to false memory. An exception is the generation effect. Using the Deese/Roediger–McDermott (DRM) paradigm, Soraci et al. found that generating rather than reading list items led to an increase in true but not false memories. They argued that generation led to enhanced item-distinctiveness that drove down false memory production. In the current study, we investigated the effects of generative processing on valenced stimuli and after a delayed (...) retention interval to examine factors that may lead to a generation effect that increases false memories. At the immediate test, false recognition rates for both negative and neutral valanced critical lures were similar across read and generate conditions. However, after a one-week delay, we saw a valence differentiation, with a generation effect for false recognition but only for negative stimuli. The roles of item-specific and relational processing during encoding and their interaction with long-term retention are discussed. (shrink)

Subthalamic nucleus deep brain stimulation is an established therapy for Parkinson’s disease motor symptoms. The ideal site for implantation within STN, however, remains controversial. While many argue that placement of a DBS lead within the sensorimotor territory of the STN yields better motor outcomes, others report similar effects with leads placed in the associative or motor territory of the STN, while still others assert that placing a DBS lead “anywhere within a 6-mm-diameter cylinder centered at the presumed middle of the (...) STN produces similar clinical efficacy.” These discrepancies likely result from methodological differences including targeting preferences, imaging acquisition and the use of brain atlases that do not account for patient-specific anatomic variability. We present a first-in-kind within-patient demonstration of severe mood side effects and minimal motor improvement in a Parkinson’s disease patient following placement of a DBS lead in the limbic/associative territory of the STN who experienced marked improvement in motor benefit and resolution of mood side effects following repositioning the lead within the STN sensorimotor territory. 7 Tesla magnetic resonance imaging data were used to generate a patient-specific anatomical model of the STN with parcellation into distinct functional territories and computational modeling to assess the relative degree of activation of motor, associative and limbic territories. (shrink)

We present a one per cent measurement of the cosmic distance scale from the detections of the baryon acoustic oscillations in the clustering of galaxies from the Baryon Oscillation Spectroscopic Survey, which is part of the Sloan Digital Sky Survey III. Our results come from the Data Release 11 sample, containing nearly one million galaxies and covering approximately 8500 square degrees and the redshift range 0.2 < z < 0.7. We also compare these results with those from the publicly released (...) DR9 and DR10 samples. Assuming a concordance Λ cold dark matter cosmological model, the DR11 sample covers a volume of 13 Gpc3 and is the largest region of the Universe ever surveyed at this density. We measure the correlation function and power spectrum, including density-field reconstruction of the BAO feature. The acoustic features are detected at a significance of over 7σ in both the correlation function and power spectrum. Fitting for the position of the acoustic features measures the distance relative to the sound horizon at the drag epoch, rd, which has a value of rd,fid = 149.28 Mpc in our fiducial cosmology. We find DV = at z = 0.32 and DV = at z = 0.57. At 1.0 per cent, this latter measure is the most precise distance constraint ever obtained from a galaxy survey. Separating the clustering along and transverse to the line of sight yields measurements at z = 0.57 of DA = and H =. Our measurements of the distance scale are in good agreement with previous BAO measurements and with the predictions from cosmic microwave background data for a spatially flat CDM model with a cosmological constant. © 2014 The Author Published by Oxford University Press on behalf of the Royal Astronomical Society. (shrink)

What does it mean to be a good thinker? Which virtues work together in someone who possesses good intellectual character? Although recent research on virtues has highlighted the benefits of individual intellectual virtues, being an excellent thinker is likely a function of possessing multiple intellectual virtues. Specifically, a good thinker would both recognize one’s intellectual shortcomings and possess an eagerness to learn driven by virtues such as love of knowledge, curiosity, and open-mindedness. Good intellectual character may only successfully manifest when (...) individuals possess not just one or a few intellectual virtues, but a larger set of such virtues to different degrees. However, little is currently known about what combination of virtues are necessary for good thinking. We argue that it is important to identify and clarify the nature of the good thinker and outline a profile methodology for achieving this goal. This approach characterizes the good thinker in terms of a profile of multiple intellectual virtues. Understanding this profile can allow greater insight into the extent to which people possess such a profile, and the potential for societal benefits of educating for these qualities. (shrink)

Checklists have been used to improve quality in many industries, including healthcare. The use of checklists, however, has not been extensively evaluated in clinical ethics consultation. This article seeks to fill this gap by exploring the efficacy of using a checklist in ethics consultation, as tested by an empirical investigation of the use of the checklist at a large academic medical system (Cleveland Clinic). The specific aims of this project are as follows: (1) to improve the quality of ethics consultations (...) by providing reminders to ethics consultants about process steps that are important for most patient-centered ethics consultations, (2) to create consistency in the ethics consultation process across the medical system, and (3) to establish an effective educational tool for trainers and trainees in clinical ethics consultation. The checklist was developed after a thorough literature review and an iterative process of revising and testing by a group of experienced ethics consultants. To pilot test the checklist, it was distributed to 46 ethics consultants. After a six-month pilot period in which ethics professionals used the checklist during their clinical activities, a survey was distributed to all of those who used the checklist. The 10-item survey examined consultants’ perceptions regarding the three aims listed above. Of the 25 survey respondents, 11 self-reported as experts in ethics consultation, nine perceived themselves to have mid-level expertise, and five self-reported as novices. The majority (68 percent) of all respondents, regardless of expertise, believed that the checklist could be a “helpful” or “very helpful” tool in the consultation process generally. Novices were more likely than experts to believe that the checklist would be useful in conducting consultations. The limitations of this study include: reduced generalizability given that this project was conducted at one medical system, utilized a small sample size, and used self-reported quality outcome measures. Despite these limitations, to the authors’ knowledge this is the first investigatation of the use of a checklist systematically to improve quality in ethics consultation. Importantly, our findings shed light on ways this checklist can be used to improve ethics consultation, including its use as an educational tool. The authors hope to test the checklist with consultants in other healthcare systems to explore its usefulness in different healthcare environments. (shrink)

Background: Clinical genomic implementation studies pose challenges for informed consent. Consent forms often include complex language and concepts, which can be a barrier to diverse enrollment, and these studies often blur traditional research-clinical boundaries. There is a move toward self-directed, web-based research enrollment, but more evidence is needed about how these enrollment approaches work in practice. In this study, we developed and evaluated a literacy-focused, web-based consent approach to support enrollment of diverse participants in an ongoing clinical genomic implementation study. (...) Methods: As part of the Cancer Health Assessments Reaching Many (CHARM) study, we developed a web-based consent approach that featured plain language, multimedia, and separate descriptions of clinical care and research activities. CHARM offered clinical exome sequencing to individuals at high risk of hereditary cancer. We interviewed CHARM participants about their reactions to the consent approach. We audio recorded, transcribed, and coded interviews using a deductively and inductively derived codebook. We reviewed coded excerpts as a team to identify overarching themes. Results: We conducted 32 interviews, including 12 (38%) in Spanish. Most (69%) enrolled without assistance from study staff, usually on a mobile phone. Those who completed enrollment in one day spent an average of 12 minutes on the consent portion. Interviewees found the information simple to read but comprehensive, were neutral to positive about the multimedia support, and identified increased access to testing in the study as the key difference from clinical care. Conclusions: This study showed that interviewees found our literacy-focused, web-based consent approach acceptable; did not distinguish the consent materials from other online study processes; and valued getting access to testing in the study. Overall, conducting empirical bioethics research in an ongoing clinical trial was useful to demonstrate the acceptability of our novel consent approach but posed practical challenges. (shrink)

ArgumentIn the United States, scientific knowledge is brought before the courts by way of testimony – the testimony of scientific experts. We argue that this expertise is best understoodfirstas related to the quality of the underlying scienceand thenin terms of who delivers it. Bloodstain pattern analysis (BPA), a contemporary forensic science, serves as the vaulting point for our exploration of objectivity as a metric for the quality of a science in judicial contexts. We argue that BPA fails to meet the (...) minimal standard set by Helen Longino’s social-procedural account of objectivity (1990, 2002). In light of some pressing issues for social-procedural accounts, we offer an infrastructural account of objectivity. This account offers what amounts to a friendly amendment to Longino’s account and adds to the ways in which we might analyze social-procedural objectivity. Finally, we address an issue that is pressing in the legal context: given that scientific knowledge is delivered by individuals, not communities, at least in U.S. courts, we (may) need a way to evaluate individual scientific and epistemic agents. We suggest a means for making this evaluation that is derived from our infrastructural account of objectivity. (shrink)

An assurance case is a structured argument, typically produced by safety engineers, to communicate confidence that a critical or complex system, such as an aircraft, will be acceptably safe within its intended context. Assurance cases often inform third party approval of a system. One emerging proposition within the trustworthy AI and autonomous systems (AI/AS) research community is to use assurance cases to instil justified confidence that specific AI/AS will be ethically acceptable when operational in well-defined contexts. This paper substantially develops (...) the proposition and makes it concrete. It brings together the assurance case methodology with a set of ethical principles to structure a principles-based ethics assurance argument pattern. The principles are justice, beneficence, non-maleficence, and respect for human autonomy, with the principle of transparency playing a supporting role. The argument pattern—shortened to the acronym PRAISE—is described. The objective of the proposed PRAISE argument pattern is to provide a reusable template for individual ethics assurance cases, by which engineers, developers, operators, or regulators could justify, communicate, or challenge a claim about the overall ethical acceptability of the use of a specific AI/AS in a given socio-technical context. We apply the pattern to the hypothetical use case of an autonomous ‘robo-taxi’ service in a city centre. (shrink)

Of the various loci of systematic theology that call for sustained philosophical investigation, the doctrine of sanctification stands out as a prime candidate. In response to that call, William Alston developed three models of the sanctifying work of the Holy Spirit: the fiat model, the interpersonal model, and the sharing model. In response to Alston’s argument for the sharing model, this paper offers grounds for a reconsideration of the interpersonal model. We close with a discussion of some of the implications (...) of one’s understanding of the transforming work of the Holy Spirit for practical Christian spirituality. (shrink)

Based on an unfinished manuscript by the late philosopher Dallas Willard, this book makes the case that the 20th century saw a massive shift in Western beliefs and attitudes concerning the possibility of moral knowledge, such that knowledge of the moral life and of its conduct is no longer routinely available from the social institutions long thought to be responsible for it. In this sense, moral knowledge--as a publicly available resource for living--has disappeared. Via a detailed survey of main developments (...) in ethical theory from the late 19th through the late 20th centuries, Willard explains philosophy's role in this shift. In pointing out the shortcomings of these developments, he shows that the shift was not the result of rational argument or discovery, but largely of arational social forces--in other words, there was no good reason for moral knowledge to have disappeared. The Disappearance of Moral Knowledge is a unique contribution to the literature on the history of ethics and social morality. Its review of historical work on moral knowledge covers a wide range of thinkers including T.H Green, G.E Moore, Charles L. Stevenson, John Rawls, and Alasdair MacIntyre. But, most importantly, it concludes with a novel proposal for how we might reclaim moral knowledge that is inspired by the phenomenological approach of Knud Logstrup and Emmanuel Levinas. Edited and eventually completed by three of Willard's former graduate students, this book marks the culmination of Willard's project to find a secure basis in knowledge for the moral life. (shrink)

The existence of free will has been both an enduring presumption of Western culture and a subject for debate across disciplines for millennia. However, little empirical evidence exists to support the almost unquestioned assumption that, in general, Westerners endorse the existence of free will. The few studies that measure belief in free will have methodological problems that likely resulted in underestimating the true extent of belief. Recently, Rakos et al. (Behavior and Social Issues 17:20–39, 2008 ) found a stronger endorsement (...) of free will when demand characteristics were eliminated. The current study builds on this work by sampling incarcerated adolescents and adults, whose freedom to act is externally constrained. Belief in free will as well as attitudes toward punishment, self-esteem, and locus of control were measured. The results indicate that free will is strongly endorsed in Western society even when freedom to act is severely restricted. However, incarcerated adolescents endorsed free will to a slightly lesser extent than their nonincarcerated counterparts from Rakos et al. (Behavior and Social Issues 17:20–39, 2008 ), while incarcerated and nonincarcerated adults offered equally strong endorsements. The comparable endorsement by adults is consistent with the hypothesis that the belief in agency is an evolutionary adaptation. The small decrease found for incarcerated adolescents may reflect the interaction between developmental factors and the expression of an evolutionary adaptation. Additionally, incarcerated adolescents and adults associated beliefs in free will with viewing punishment as a means of deterrence, rehabilitation, and retribution. Incarcerated adults, but not incarcerated adolescents, associated beliefs in free will with greater self-esteem and with an external locus of control. Finally, though both incarcerated adults and adolescents endorsed free will strongly, the former manifested the belief by emphasizing free agentic choice whereas the latter focused on the personal responsibility that is interwoven with free choice. The implications of these findings are discussed in the context of evolutionary, cultural, and developmental factors. (shrink)

Against various detractors , this book develops a foundationalist theory of epistemic justification. In contrast with Laurence BonJour and borrowing from John McDowell, the essential argument is that conceptualized perpetual experience provides a non-doxastic foundation for perceptual beliefs about physical objects.

Using qualitative data based on interviews with 22 married infertile couples living in western New York State, we describe the ways in which husbands and wives interact in the process of constructing their infertility. The wives experienced infertility as a cataclysmic role failure. Husbands tended to see infertility as a disconcerting event but not as a tragedy. Couples tended to see infertility as a problem for wives. Frustration and lack of communication were typical consequences of the confrontation of husbands' and (...) wives' perspectives on infertility. Interactions with medical professionals tended to reinforce these consequences. These interactions between wives, husbands, and medical professionals may lead to taking wrong directions in treatment and to ignoring treatment options. Some of the problems we describe could be lessened by adopting a model of couple-centered treatment in a setting that incorporated routine counseling. (shrink)