The FDA's new table of surrogate endpoints used for drug approvals is an important step forward for overseeing the use of biomarkers in clinical trials. Nevertheless, we present several ways in which the table can be improved.

When we hear about a transgression, we may consider whether the perpetrator’s individual circumstances make their transgression more understandable or excusable. Mitigating circumstances may reduce the severity of punishment that is deemed appropriate, both intuitively and legally. But importantly, in courts of public opinion and of law, mitigating information is typically presented only after information about a perpetrator’s transgression. We explore whether this sequence influences the force of mitigating evidence. Specifically, in two studies, we examined whether presenting evidence about a (...) perpetrator’s background before or after evidence of their violation influenced how severely U.S. participants punished perpetrators. In Study 1 (N = 132), evidence about the perpetrator’s mitigating circumstances reduced punishment only when it was presented before evidence about the perpetrator’s violation. Study 2 (N = 316) additionally revealed this moderating effect of presentation order across a variety of premeditated and impulsive violations. These findings are consistent with person-centered theories of punishment and with the Story Model of adjudication. (shrink)

The objective of this study was to assess the beliefs of parents of youth soccer players about Chronic Traumatic Encephalopathy, concussion, and retirement from sport decisions and compare them to those of concussion-specialized clinicians. An electronic survey was completed by parents of youth club soccer players and concussion-specialized clinicians located in a large U.S. urban center. Parents believed more strongly in the causal relationship between concussions and CTE, and between CTE and harm than did clinicians. Parents who themselves had participated (...) in sport at a high level had more conservative beliefs than other parents about the number of concussions after which an athlete should retire from contact or collision sport. Results are discussed in the context of ethical risk communication between clinicians and parents. This includes the importance of communicating information about CTE to parents and youth athletes in an understandable way so that they can make informed choices about contact and collision sport participation. Further research is encouraged to evaluate approaches of communicating evidence about CTE to a diverse population of families of youth athletes. (shrink)

The COVID-19 pandemic has been devastating for people living with dementia (PLWD) and their caregivers. While prior research has documented these effects, it has not delved into their specific causes or how they are modified by contextual variation in caregiving circumstances.

Over the course of human life, health care decision‐making is often interdependent. In this article, we use “interdependence” to refer to patients’ engagement of nonclinicians—for example, family members or trusted friends—to reach health care decisions. Interdependence, we suggest, is common for patients in all stages of life, from early childhood to late adulthood. This view contrasts with the common bioethical assumption that medical decisions are either wholly independent or dependent and that independence or dependence is tightly coupled with a person's (...) decision‐making capacity. In this article, we array various approaches to decision‐making along a continuum of interdependence. An appreciation of this continuum can empower patients and elucidate ethical challenges that arise when people transition between different kinds of interdependence across the life span. (shrink)

BackgroundWhen conducting research with Indigenous populations consent should be sought from both individual participants and the local community. We aimed to search and summarise the literature about methods for seeking consent for research with Indigenous populations.MethodsA systematic literature search was conducted for articles that describe or evaluate the process of seeking informed consent for research with Indigenous participants. Guidelines for ethical research and for seeking consent with Indigenous people are also included in our review.ResultsOf 1447 articles found 1391 were excluded (...) ; 56 were relevant and included. Articles were categorised into original research that evaluated the consent process or publications detailing the process of seeking consent and guidelines for ethical research. Guidelines were categorised into international ; national and state/regional/local guidelines. In five studies based in Australia, Canada and The United States of America the consent process with Indigenous people was objectively evaluated. In 13 other studies interpreters, voice recording, videos, pictures, flipcharts and “plain language” forms were used to assist in seeking consent but these processes were not evaluated. Some Indigenous organisations provide examples of community-designed resources for seeking consent and describe methods of community engagement, but none are evaluated. International, national and local ethical guidelines stress the importance of upholding Indigenous values but fail to specify methods for engaging communities or obtaining individual consent. In the ‘Grey literature’ concerns about the consent process are identified but no solutions are offered.ConclusionConsultation with Indigenous communities is needed to determine how consent should be sought from the community and the individual, and how to evaluate this process. (shrink)

The rule of rescue describes the moral impulse to save identifiable lives in immediate danger at any expense. Think of the extremes taken to rescue a small child who has fallen down a well, a woman pinned beneath the rubble of an earthquake, or a submarine crew trapped on the ocean floor. No effort is deemed too great. Yet should this same moral instinct to rescue, regardless of cost, be applied in the emergency room, the hospital, or the community clinic? (...) -/- In health care, the desire to save lives at any cost must be reconciled with the reality of resource scarcity. As one example, the estimated cost for prophylactic Factor VIII to treat one patient with hemophilia for one year is $300,000. Costs of this magnitude have been accepted by public and private insurers in the developed world, even though, in principle, these sums could provide greater overall health benefit if allocated to pay for the unmet health care needs of many other patients. Looking forward, however, broad application of the rule of rescue will be increasingly untenable. But the moral instinct will remain: the desire to help those weakest among us, especially when their small numbers allow us to see them as unique individuals. What, then, is the ethical framework that can guide coverage and reimbursement decisions for orphan drugs into the future? (shrink)

The consent and community engagement process for research with Indigenous communities is rarely evaluated. Research protocols are not always collaborative, inclusive or culturally respectful. If participants do not trust or understand the research, selection bias may occur in recruitment, affecting study results potentially denying participants the opportunity to provide more knowledge and greater understanding about their community. Poorly informed consent can also harm the individual participant and the community as a whole. Invited by local Aboriginal community leaders of the Fitzroy (...) Valley, the Kimberley, Western Australia, The Picture Talk project explores the consent process for research. Focus groups of Aboriginal community members were conducted to establish preferences for methods of seeking individual consent. Transcripts were analysed through NVivo10 Qualitative software using grounded theory with inductive and deductive coding. Themes were synthesised with quotes highlighted. Focus groups with Aboriginal community members were facilitated by a Community Navigator as a cultural guide and interpreter and a researcher. Participants were recruited from all main language groups of the Fitzroy Valley – Gooniyandi, Walmajarri, Wangkatjungka, Bunuba and Nikinya. Participants were aged ≥18 years, with 5 female groups and one male group. Themes identified include: Reputation and trust is essential; The Community Navigator is key; Pictures give the words meaning – milli milli versus Pictures; Achieving consensus in circles; Signing for consent; and Research is needed in the Valley. Aboriginal communities of the Fitzroy Valley recommend that researchers collaborate with local leaders, develop trust and foster a good reputation in the community prior to research. Local Aboriginal researchers should be employed to provide cultural guidance throughout the research process and interpret local languages especially for elders. Pictures are preferred to written text to explain research information and most prefer to sign for consent. The Fitzroy Valley welcomes research when collaborative and for the benefit of the community. Future research could include exploring how to support young people, promote health screening and improve understanding of medical knowledge. (shrink)

Around the world, a growing number of communities are voicing their demands for authority in the governance of research involving them. Many such communities have experienced histories of exploitative, stigmatizing, intrusive research that failed to benefit them. To better understand what strategies communities are developing in order to have a say in research oversight, we conducted a scoping review of the international peer-reviewed and grey literature. Three primary strategies were identified: (1) guidelines; (2) community review boards; and (3) community advisory (...) boards. Guidelines include documents developed by, with, or for communities to outline ethical behavior or conduct in research with or within the community. Community review boards offer ethical review of research protocols, much like traditional research ethics boards, but are community led and focus on community interests. Community advisory boards consist of representatives from a given community and are developed to advise institutions or research teams on community-level ethical matters pertaining to research projects. Initiatives led by Indigenous communities far outnumbered others in the sample, reflecting the legacy of continuous Indigenous resistance to research as a tool of colonialism. In several cases, communities in marginalized neighbourhoods, where harmful and exploitative research practices have taken place, emphasized the significance of community-led governance grounded in shared geographical and social contexts. We discuss some of the beneficial and challenging features of each type of strategy and offer recommendations for stakeholders who wish to support community-led efforts in research ethics. (shrink)

Humans routinely modify their walking speed to adapt to functional goals and physical demands. However, damage to the central nervous system often results in abnormal modulation of walking speed and increased risk of falls. There is considerable interest in treatment modalities that can provide safe and salient training opportunities, feedback about walking performance, and that may augment less reliable sensory feedback within the CNS after injury or disease. Fully immersive virtual reality technologies show benefits in boosting training-related gains in walking (...) performance; however, they lack views of the real world that may limit functional carryover. Augmented reality and mixed reality head-mount displays provide partially immersive environments to extend the virtual reality benefits of interacting with virtual objects but within an unobstructed view of the real world. Despite this potential advantage, the feasibility of using MR-HMD visual feedback to promote goal-directed changes in overground walking speed remains unclear. Thus, we developed and evaluated a novel mixed reality application using the Microsoft HoloLens MR-HMD that provided real-time walking speed targets and augmented visual feedback during overground walking. We tested the application in a group of adults not living with disability and examined if they could use the targets and visual feedback to walk at 85%, 100%, and 115% of each individual’s self-selected speed. We examined whether individuals were able to meet each target gait speed and explored differences in accuracy across repeated trials and at the different speeds. Additionally, given the importance of task-specificity to therapeutic interventions, we examined if walking speed adjustment strategies were consistent with those observed during usual overground walking, and if walking with the MR-HMD resulted in increased variability in gait parameters. Overall, participants matched their overground walking speed to the target speed of the MR-HMD visual feedback conditions. The percent inaccuracy was approximately 5% across all speed matching conditions and remained consistent across walking trials after the first overall walking trial. Walking with the MR-HMD did not result in more variability in walking speed, however, we observed more variability in stride length and time when walking with feedback from the MR-HMD compared to walking without feedback. The findings offer support for mixed reality-based visual feedback as a method to provoke goal-specific changes in overground walking behavior. Further studies are necessary to determine the clinical safety and efficacy of this MR-HMD technology to provide extrinsic sensory feedback in combination with traditional treatments in rehabilitation. (shrink)

Cognitively engaging physical activity has been suggested to have superior effects on cognition compared to PA with low cognitive demands; however, there have been few studies directly comparing these different types of activities. The aim of this study is to compare the cognitive effects of a combined physically and cognitively engaging bout of PA to a physical or cognitive activity alone in children. Children were randomized in pairs to one of three 20-min conditions: a cognitive sedentary activity; a non-cognitively engaging (...) PA; and a cognitively engaging PA. Executive function was assessed using a modified Eriksen flanker task immediately before and 10–15 min following the experimental condition. Children ages 6–8 years were included in the study. A repeated measures ANOVA found no significant difference between groups with respect to scores on the flanker task. The results do not support the hypotheses that a cognitively engaging bout of PA enhances cognitive performance over non-cognitively engaging PA or sedentary activities. Possible explanations for our findings include overexertion during the acute bout of PA and depletion of positive affect prior to performing the post-intervention EF tasks. (shrink)

Using medical advances to enhance human athletic, aesthetic, and cognitive performance, rather than to treat disease, has been controversial. Little is known about physicians? experiences, views, and attitudes in this regard. We surveyed a national sample of physicians to determine how often they prescribe enhancements, their views on using medicine for enhancement, and whether they would be willing to prescribe a series of potential interventions that might be considered enhancements. We find that many physicians occasionally prescribe enhancements, but doctors hold (...) nuanced and ambiguous views of these issues. Most express concerns about the potential effects of enhancements on social equity, yet many also believe specific enhancements that are safe and effective should be available but not covered by insurance. These apparently contradictory views might reflect inherent tensions between the values of equity and liberty, which could make crafting coherent social policies on medical enhancements challenging. [Supplementary materials are available for this article. Go to the publisher's online edition of American Journal of Bioethics for the following free supplemental resource(s): An additional table (Table 5) referred to on p. 5]. (shrink)

__Improving Education Together _offers a step-by-step guide to Labor-Management-Community (LMC) collaboration, an intervention that has successfully improved student outcomes in a wide variety of school districts across the country._ The authors illustrate how a culture of collaboration between labor, management, and community stakeholders can be built using readily available tools for needs assessment, root-cause analysis, team norms, brainstorming, consensus-building, and long-term planning. _Improving Education Together _offers detailed examples of how districts across the country—including Massachusetts, Maryland, and Illinois—have successfully implemented the (...) LMC approach, along with resources and strategies employed and lessons learned from obstacles and setbacks encountered along the way. Timely, useful, and accessible, this guide will appeal to a broad audience of school leaders, board members, and community leaders eager to learn more about how to collectively lead and manage school district change that is sustainable and results in improved teaching and learning. (shrink)

Koonin argues that CRISPR-Cas systems present the best-known case in point for Lamarckian evolution because they satisfy his proposed criteria for the specific inheritance of acquired adaptive characteristics. We see two interrelated issues with Koonin’s characterization of CRISPR-Cas systems as Lamarckian. First, at times he appears to confuse an account of the CRISPR-Cas system with an account of the mechanism it employs. We argue there is no evidence for the CRISPR-Cas system being “Lamarckian” in any sense. Second, it is unclear (...) whether the mechanism is more “Lamarckian” than many other forms of genetic change already well-characterized in Darwinian terms. We present three conceptually distinct senses in which the mechanism of IAC may be considered Lamarckian and argue that only the strongest sense of goal-directed IAC would be difficult to accommodate in a Darwinian account. As the CRISPR-Cas mechanism does not qualify as “Lamarckian” in this strong sense, we argue there is no conceptual value in calling it “Lamarckian”. Finally, we suggest that CRISPR-Cas systems do hold the potential for genuinely non-Darwinian, directed evolution in a way that Koonin did not discuss, involving their potential use as a human gene-editing tool. (shrink)

The online processing of both music and language involves making predictions about upcoming material, but the relationship between prediction in these two domains is not well understood. Electrophysiological methods for studying individual differences in prediction in language processing have opened the door to new questions. Specifically, we ask whether individuals with musical training predict upcoming linguistic material more strongly and/or more accurately than non-musicians. We propose two reasons why prediction in these two domains might be linked: Musicians may have greater (...) verbal short-term/working memory; music may specifically reward predictions based on hierarchical structure. We provide suggestions as to how to expand upon recent work on individual differences in language processing to test these hypotheses. (shrink)

Biomarkers can be powerful tools to guide diagnosis, treatment, and research. However, prudent use of biomarkers requires formal validation efforts. Although the data needed for biomarker validation has traditionally been hard to access, new research initiatives can ease this process.

Le sens du nom grec de φύσις, et celui de la physique aristotélicienne, sont au cœur de la compréhension heideggerienne de la métaphysique, qu’il s’agisse, dans les années 1920, de refonder celle-ci en retrouvant ses possibilités initiales, ou, à la fin des années 1930, de l’assumer pour pouvoir la dépasser, puis de la laisser. De part et d’autre du tournant, la φύσις, dans sa surabondance et dans son dépliement, permet en effet de rendre compte de l’émergence de deux domaines, ceux (...) de la physique et de la métaphysique. Toutefois, la plurivocité diachronique et synchronique de φύσις, telle qu’elle est mise en lumière en 1929-1930, se trouve ensuite comprise de manière plus radicale. Il ne s’agit plus de repérer l’évolution du sens de φύσις et la coexistence de significations contemporaines, mais de mettre au jour le télescopage, dans la pensée aristotélicienne, de deux significations qui diffèrent de manière historiale. (shrink)

Requests for support in professional changes are getting more and more numerous. Regarding jobs concerned with caring for others, therapeutic education needs to be spread into new approaches requiring social and human sciences (Tourette-Turgis, 2015 ; Chalmel, 2015). These requests lead to alterations in professional practices and changes in educational devices. This chapter deals with a direct observation of effective practices addressed to young patients and also implies the training of nurses through experiences. It also discusses ways of scientific collaboration (...) between female researchers in different scientific fields of the medical body leading the latter to alter their practices by creating pedagogic instruments or new tools for training. This inventive conception deriving from these exchanges leaning on experiences and skills previously built up and linked together to help devices development. Our contribution deals with and discusses the transformation of state nurses functions through these analyses and towards actions which do not only concern body care but a way of teaching healthy life style. The themes under study concerns the passing on and transferring experiences and responsibility when directing cessions from cardiology education to the therapeutic education nurse. (shrink)

The thymus is a unique primary lymphoid organ that supports the production of self‐tolerant T‐cells essential for adaptive immunity. Intrathymic microenvironments are microanatomically compartmentalised, forming defined cortical, and medullary regions each differentially supporting critical aspects of thymus‐dependent T‐cell maturation. Importantly, the specific functional properties of thymic cortical and medullary compartments are defined by highly specialised thymic epithelial cells (TEC). For example, in the medulla heterogenous medullary TEC (mTEC) contribute to the enforcement of central tolerance by supporting deletion of autoreactive T‐cell (...) clones, thereby counterbalancing the potential for random T‐cell receptor generation to contribute to autoimmune disease. Recent advances have further shed light on the pathways and mechanisms that control heterogeneous mTEC development and how differential mTEC functionality contributes to control self‐tolerant T‐cell development. Here we discuss recent findings in relation to mTEC development and highlight examples of how mTEC diversity contribute to thymus medulla function. (shrink)

There is a growing trend of refusal of blood transfusions from COVID-19 vaccinated donors. We highlight three cases where parents have refused blood transfusions from COVID-19 vaccinated donors on behalf of their children in the setting of congenital cardiac surgery. These families have also requested accommodations such as explicit identification of blood from COVID-19 vaccinated donors, directed donation from a COVID19 unvaccinated family member, or use of a non-standard blood supplier. We address the ethical challenges posed by these issues. We (...) describe the current screening and safety processes for standard blood donation and explore the importance of donor anonymity and challenges with directed donation and non-standard blood suppliers. We present an ethical framework using the Best Interest Standard, the Zone of Parental Discretion, and the Harm Principle when considering these refusals. Finally, we provide recommendations for how to approach these requests as they potentially become more commonplace in pediatrics. (shrink)

La pratique du copier-coller chez les étudiant.e.s est assimilée à du plagiat et la réponse apportée par l’institution se résume à « surveiller et punir ». Cette pratique mérite cependant d’être interrogée dans le cadre des littératies universitaires par rapport à la nécessaire prise en compte des littératies numériques. Le fait qu’elle soit conçue comme une « méconduite » d’un point de vue déontologique est à comprendre par rapport à un cadre normatif qui en appelle à l’honnêteté académique et institue (...) l’auteur et les sources comme des composantes essentielles des écrits de savoirs, sans guère en expliciter les enjeux. Comment penser le copier-coller et qu’en faire? En quoi peut-on passer de l’inacceptable au didactisable, et que prendre en compte? Dans la perspective d’une réflexivité critique dans le champ des littératies universitaires, nous proposons des éléments de contextualisation qui permettent de problématiser le copier-coller, en tant que geste d’écriture, en tant qu’objet de débats, et de manière à mieux outiller les étudiant.e.s face aux attentes universitaires et en termes de compétences littéraciques en général. Nous nous intéressons à la réception du copier-coller, à l’énonciation par copier-coller et aux confusions qui entourent les attentes à l’égard des écrits des étudiant.e.s. Le contexte est compris comme un cadre interprétatif qui sert à construire un objet didactique en tant que tel. (shrink)

The growing block view of time holds that the past and present are real whilst the future is unreal; as future events become present and real, they are added on to the growing block of reality. Surprisingly, given the recent interest in this view, there is very little literature on its origins. This paper explores those origins, and advances two theses. First, I show that although C. D. Broad’s Scientific Thought provides the first defence of the growing block theory, the (...) theory receives its first articulation in Samuel Alexander’s Space, Time, and Deity. Further, Alexander’s account of deity inclines towards the growing block view. Second, I argue that Broad shifted towards the growing block theory as a result of his newfound conviction that time has a direction. By way of tying these theses together, I argue that Broad’s views on the direction of time – and possibly even his growing block theory – are sourced in Alexander. (shrink)

Since the early 1980’s, with the clinical advent of in vitro fertilization resulting in so-called “test tube babies,” a wide array of ethical considerations and concerns regarding artificial womb technology (AWT) have been described. Recent breakthroughs in the development of extracorporeal neonatal life support by means of AWT have reinitiated ethical interest about this topic with a sense of urgency. Most of the recent ethical literature on the topic, however, pertains not to the more imminent scenario of a physiologically improved (...) method of neonatal care through AWT, but instead to the remote scenario of “complete ectogenesis” that imagines human gestation occurring entirely outside of the womb. This scoping review of the ethical literature on AWT spans from more abstract concerns about complete ectogenesis to more immediate concerns about the soon-to-be-expected clinical life support of what we term the fetal neonate or fetonate. Within an organizing framework of different stages of human gestational development, from conception to the viable premature infant, we discuss both already identified and newly emerging ethical considerations and concerns regarding AWT and the care of the fetonate. (shrink)

Dans cet article, nous présentons une étude de faisabilité sur l’annotation des passages entre guillemets, phénomènes linguistiques polyphoniques qui résistent souvent à une lecture univoque et à un schéma d’annotation simplificateur. La faisabilité de l’annotation a été testée à travers une étude inter-annotateurs qui a montré, avec un accord pour 80% des annotations effectuées, que des valeurs stables (dénomination, citation, autonymie, commentaires modalisants) pouvaient être postulées. Les cas de désaccord, en partie inévitables face à la complexité du phénomène, peuvent être (...) en partie réduits par un repérage systématique des marques formelles (marques typo-dispositionnelles, éléments du lexique et formules syntaxiques) et un inventaire détaillé des contextes d’emploi pour chaque valeur. Certaines valeurs demeurant ambiguës, il convient toutefois de prévoir dans l’annotation des cas de cumul de valeurs (le passage entre guillemets cumule plusieurs valeurs compatibles) ou d’ambiguïtés (plusieurs interprétations différentes sont possibles) en cas de désaccord des annotateurs. (shrink)

Le film Coup pour coup de Marin Karmitz met en scène, peu avant la grève, une ouvrière en proie à la « crise de nerfs ». Tout en confrontant les représentations liées à la « crise de nerfs » aux réalités des années 68, il s’agit, dans une approche psychodynamique, d’analyser ce qui se joue dans le passage de la souffrance individuelle que constitue la « crise de nerfs » à l’identification puis à la résistance collective des ouvrières.

Des premiers jeux vidéo aux jeux actuels, les interfaces numériques tout autant que les genres de jeux vidéo se sont diversifiés, multipliant les modalités d’identification du joueur et de manipulation des personnages . Intermédiaire entre le monde du joueur et le monde du jeu, l’avatar est devenu un dispositif complexe et hybride : les limites entre le joueur et le personnage tendent à s’atténuer. Afin de mettre en évidence les lignes directrices de cette évolution des avatars dans les jeux vidéo, (...) cette contribution, s’appuie sur un état de la recherche des travaux portant sur l’avatar et l’identification du joueur, et propose une typologie des avatars sous l’angle des moda- lités d’identification du joueur à son personnage : l’avatar-marionnette, l’avatar-masque et l’avatar-mouvement.Since the first video games, digital interfaces as well as video game genres have become greatly diversified, with many different methods for identifying with and manipulating game characters . The avatar, the intermediary between the world of the gamer and the world of the game itself, has become a complex, hybrid figure where the boundaries between player and character are increasingly blurred. To highlight the main trends in the changing figure of the avatar in video games, this paper draws on cur- rent research on avatars and player identification to put for- ward a typology based on different means used by players to identify with their characters: puppet avatars, mask avatars and motion-based avatars. (shrink)