Ageing causes progressive decline in metabolic, behavioural, and physiological functions, leading to a reduced health span. The extracellular matrix (ECM) is the three‐dimensional network of macromolecules that provides our tissues with structure and biomechanical resilience. Imbalance between damage and repair/regeneration causes the ECM to undergo structural deterioration with age, contributing to age‐associated pathology. The ECM ‘Ageing Across the Life Course’ interdisciplinary research network (ECMage) was established to bring together researchers in the United Kingdom, and internationally, working on the emerging field (...) of ECM ageing. Here we report on a consultation at a joint meeting of ECMage and the Medical Research Council / Versus Arthritis Centre for Integrated Research into Musculoskeletal Ageing, held in January 2023, in which delegates analysed the key questions and research opportunities in the field of ECM ageing. We examine fundamental biological questions, enabling technologies, systems of study and emerging in vitro and in silico models, alongside consideration of the broader challenges facing the field. (shrink)

What does it mean to consider the world of AI through a Christian lens? Rapid developments in AI continue to reshape society, raising new ethical questions and challenging our understanding of the human person. Encountering Artificial Intelligence draws on Pope Francis’ discussion of a culture of encounter and broader themes in Catholic social thought in order to examine how current AI applications affect human relationships in various social spheres and offers concrete recommendations for better implementation. The document also explores questions (...) regarding personhood, consciousness, and the kinds of relationships humans might have with even the most advanced AI. Through these discussions, this book investigates the theoretical and practical challenges to interpersonal encounter raised by the age of AI. (AI Research Group for the Centre for Digital Culture of the Dicastery of Culture and Education of the Holy See). (shrink)

In this paper I give a definition of assertion that develops William P. Alston’s account. Alston’s account of assertion combines a responsibility condition R, which captures the appropriate socio-normative status that one undertakes in asserting something, with an explicit presentation condition, such that the speech act in some way presents the content of what is being asserted. I develop Alston’s account of explicit presentation and add a Brandomian responsibility condition. I then argue that this produces an attractive position on the (...) nature of assertion. (shrink)

Experiments have suggested that umbilical cord blood stem cells can be used to prevent diseases such as atherosclerosis. This paper discusses ethical issues surrounding such usage such as the uncertainty that individuals at risk of a disease will actually get the disease; issues related to research with children; safety issues; from where these stem cells would be obtained; and whether these usages should be considered as therapies or as physical enhancements.

In many disciplines, mediating processes are usually investigated with randomized experiments and linear regression to determine if the treatment affects the outcome through a mediator. However, randomizing the treatment will not yield accurate causal direct and indirect estimates unless certain assumptions are satisfied since the mediator status is not randomized. This study describes methods to estimate causal direct and indirect effects and reports the results of a large Monte Carlo simulation study on the performance of the ordinary regression and modern (...) causal mediation analysis methods, including a previously untested doubly robust sequential g-estimation method, when there are confounders of the mediator-to-outcome relation. Results show that failing to measure and incorporate potential post-treatment confounders in a mediation model leads to biased estimates, regardless of the analysis method used. Results emphasize the importance of measuring potential confounding variables and conducting sensitivity analysis. (shrink)

Assertion is a speech act that stands at the intersection of the philosophy of language and social epistemology. It is a phenomenon that bears on such wide-ranging topics as testimony, truth, meaning, knowledge and trust. It is thus no surprise that analytic philosophers have devoted innumerable pages to assertion, trying to give the norms that govern it, its role in the transmission of knowledge, and most importantly, what assertion is, or how assertion is to be defined. -/- In this thesis (...) I attempt to show that all previous answers to the question “What is assertion?” are flawed. There are four major traditions in the literature: constitutive norm theories of assertion, accounts that treat assertion as the expression of speaker attitudes, accounts that treat assertion as a proposal to add some proposition to the common ground, and accounts that treat assertion as the taking of responsibility for some claim. Each tradition is explored here, the leading theories within the tradition developed, and then placed under scrutiny to demonstrate flaws within the positions surveyed. -/- I follow the work of G.E. Moore and William P. Alston, whilst drawing on the work of Robert Brandom in order to give a new bipartite theory of assertion. I argue that assertion consists in the explicit presentation of a proposition, along with a taking of responsibility for that proposition. Taking Alston’s explicit presentation condition and repairing it in order to deal with problems it faces, whilst combining it with Brandom’s responsibility condition, provides, I believe, the best account of assertion. (shrink)

Interest in science and math plays an important role in encouraging STEM motivation and career aspirations. This interest decreases for girls between late childhood and adolescence. Relatedly, positive mentoring experiences with female teachers can protect girls against losing interest. The present study examines whether visitors to informal science learning sites differ in their expressed science and math interest, as well as their science and math stereotypes following an interaction with either a male or female educator. Participants were visitors to one (...) of four ISLS in the United States and United Kingdom. Following an interaction with a male or female educator, they reported their math and science interest and responded to math and science gender stereotype measures. Female participants reported greater interest in math following an interaction with a female educator, compared to when they interacted with a male educator. In turn, female participants who interacted with a female educator were less likely to report male-biased math gender stereotypes. Self-reported science interest did not differ as a function of educator gender. Together these findings suggest that, when aiming to encourage STEM interest and challenge gender stereotypes in informal settings, we must consider the importance of the gender of educators and learners. (shrink)

In this article applied and theoretical epistemologies benefit each other in a study of the British legal case of R. vs. Clark. Clark's first infant died at 11 weeks of age, in December 1996. About a year later, Clark had a second child. After that child died at eight weeks of age, Clark was tried for murdering both infants. Statisticians and philosophers have disputed how to apply Bayesian analyses to this case, and thereby arrived at different judgments about it. By (...) dwelling on this applied case, I make theoretical gains: clarifying and defending pragmatic principles of inference that are important for estimating key probabilities in a range of cases. Then, partly by drawing on such principles, and uncovering overlooked data on post-partum psychosis, I make applied gains: improving the rationality of judgments about the Sally Clark case in particular, judgments important to future similar cases. (shrink)

The focus of this study was to analyze the content, distribution, and comparative genome relationships of 996 chromosome bin-mapped expressed sequence tags accounting for 2266 restriction fragments on the homoeologous group 3 chromosomes of hexaploid wheat. Of these loci, 634, 884, and 748 were mapped on chromosomes 3A, 3B, and 3D, respectively. The individual chromosome bin maps revealed bins with a high density of mapped ESTs in the distal region and bins of low density in the proximal region of the (...) chromosome arms, with the exception of 3DS and 3DL. These distributions were more localized on the higher-resolution group 3 consensus map with intermediate regions of high-mapped-EST density on both chromosome arms. Gene ontology classification of mapped ESTs was not significantly different for homoeologous group 3 chromosomes compared to the other groups. A combined analysis of the individual bin maps using 537 of the mapped ESTs revealed rearrangements between the group 3 chromosomes. Approximately 232 of the consensus mapped ESTs matched sequences on rice chromosome 1 and revealed large- and small-scale differences in gene order. Of the group 3 mapped EST unigenes ∼21 and 32% matched the Arabidopsis coding regions and proteins, respectively, but no chromosome-level gene order conservation was detected. (shrink)

Professional statements guide neonatal resuscitation thresholds at the border of viability. A 2015 systematic review of international guidelines by Guillen et al. found considerable variability between statements’ clinical recommendations for infants at 23–24 weeks gestational age (GA). The authors concluded that differences in the type of data included were one potential source for differing resuscitation thresholds within this “ethical gray zone.” How statements present ethical considerations that support their recommendations, and how this may account for variability, has not been as (...) rigorously explored. We performed a mixed-methods exploratory analysis of 25 current international guidelines for neonatal resuscitation at 22+0−25+0 weeks GA. Qualitative analysis using a modified grounded theory yielded 34 distinct codes, eight categories, and four overarching themes. Three themes, consequentialism, principlism, and rights-based, consisted of concepts central to these ethical frameworks. The fourth theme, clinical reasoning, described counseling practices, medical management, outcomes data, and prognostic uncertainty, without any ethical context. The theme of clinical reasoning appeared in 22 of 25 guidelines. Ten guidelines lacked any ethical theme. Guidelines with an identified ethical theme were more likely to recommend comfort care than guidelines without an identified ethical theme, and recommended it at a higher average GA (22.7 weeks vs. 22.0 weeks, p = 0.03). Thus, how ethical concepts are incorporated into guidelines potentially impacts resuscitation thresholds. We argue that inclusion of explicit discussion of ethical considerations surrounding resuscitation in the “gray zone” would clarify values that inform recommendations and facilitate discussions about how neonatology ought to approach periviability as outcomes continue to evolve. (shrink)

The co-occurrence of stress-induced posttraumatic stress disorder (PTSD) and obesity is common, particularly among military personnel but the link between these conditions is unclear. Individuals with comorbid PTSD and obesity manifest other physical and psychological problems, which significantly diminish their quality of life. Current understanding of the pathways connecting stress to PTSD and obesity is focused largely on behavioral mediators alone with little consideration of the biological regulatory mechanisms that underlie their co-occurrence. In this work, we leverage prior knowledge to (...) systematically highlight such bio-behavioral mechanisms and inform on the design of confirmatory pilot studies. We use natural language processing (NLP) to extract documented regulatory interactions involved in the metabolic response to stress and its impact on obesity and PTSD from over 8 million peer-reviewed papers. The resulting network describes the propagation of stress to PTSD and obesity through 34 metabolic mediators using 302 documented regulatory interactions supported by over 10,000 citations. Stress jointly affected both conditions through 21 distinct pathways involving only two intermediate metabolic mediators out of a total of 76 available paths through this network. Moreover, oxytocin (OXT), Neuropeptide-Y (NPY), and cortisol supported an almost direct propagation of stress to PTSD and obesity with different net effects. Although stress upregulated both NPY and cortisol, the downstream effects of both markers are reported to relieve PTSD severity but exacerbate obesity. The stress-mediated release of oxytocin, however, was found to concurrently downregulate the severity of both conditions. These findings highlight how a network-informed approach that leverages prior knowledge might be used effectively in identifying key mediators like OXT though experimental verification of signal transmission dynamics through each path will be needed to determine the actual likelihood and extent of each marker’s participation. (shrink)

Progressive supranuclear palsy is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP and 3,247 controls followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the (...) stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved. (shrink)

This report describes the rationale, approaches, organization, and resource development leading to a large-scale deletion bin map of the hexaploid wheat genome. Accompanying reports in this issue detail results from chromosome bin-mapping of expressed sequence tags representing genes onto the seven homoeologous chromosome groups and a global analysis of the entire mapped wheat EST data set. Among the resources developed were the first extensive public wheat EST collection. Described are protocols for sequencing, sequence processing, EST nomenclature, and the assembly of (...) ESTs into contigs. These contigs plus singletons were used for selection of distinct sequence motif unigenes. Selected ESTs were rearrayed, validated by 5′ and 3′ sequencing, and amplified for probing a series of wheat aneuploid and deletion stocks. Images and data for all Southern hybridizations were deposited in databases and were used by the coordinators for each of the seven homoeologous chromosome groups to validate the mapping results. Results from this project have established the foundation for future developments in wheat genomics. (shrink)

In this article, we propose the Fair Priority Model for COVID-19 vaccine distribution, and emphasize three fundamental values we believe should be considered when distributing a COVID-19 vaccine among countries: Benefiting people and limiting harm, prioritizing the disadvantaged, and equal moral concern for all individuals. The Priority Model addresses these values by focusing on mitigating three types of harms caused by COVID-19: death and permanent organ damage, indirect health consequences, such as health care system strain and stress, as well as (...) economic destruction. It proposes proceeding in three phases: the first addresses premature death, the second long-term health issues and economic harms, and the third aims to contain viral transmission fully and restore pre-pandemic activity. -/- To those who may deem an ethical framework irrelevant because of the belief that many countries will pursue "vaccine nationalism," we argue such a framework still has broad relevance. Reasonable national partiality would permit countries to focus on vaccine distribution within their borders up until the rate of transmission is below 1, at which point there would not be sufficient vaccine-preventable harm to justify retaining a vaccine. When a government reaches the limit of national partiality, it should release vaccines for other countries. -/- We also argue against two other recent proposals. Distributing a vaccine proportional to a country's population mistakenly assumes that equality requires treating differently situated countries identically. Prioritizing countries according to the number of front-line health care workers, the proportion of the population over 65, and the number of people with comorbidities within each country may exacerbate disadvantage and end up giving the vaccine in large part to wealthy nations. (shrink)

Institutional Review Boards have expressed concern that research into sensitive topics such as mental disorder will cause participants undue distress. This study investigated the emotional responses of 5,220 Australians to a survey on mental-health-related discrimination. Participants were interviewed about their mental health and experiences of discrimination across 10 life domains and then the emotional impacts of the survey. Results suggested that a minority experienced a negative reaction in contrast to 88% reporting positive experiences. A mental health problem was associated with (...) both negative and positive reactions. (shrink)

All parties involved in researching, developing, manufacturing, and distributing COVID-19 vaccines need guidance on their ethical obligations. We focus on pharmaceutical companies' obligations because their capacities to research, develop, manufacture, and distribute vaccines make them uniquely placed for stemming the pandemic. We argue that an ethical approach to COVID-19 vaccine production and distribution should satisfy four uncontroversial principles: optimising vaccine production, including development, testing, and manufacturing; fair distribution; sustainability; and accountability. All parties' obligations should be coordinated and mutually consistent. For (...) instance, companies should not be obligated to provide host countries with additional booster shots at the expense of fulfilling bilateral contracts with countries in which there are surges. Finally, any satisfactory approach should include mechanisms for assurance that all parties are honouring their obligations. This assurance enables countries, pharmaceutical companies, global organisations, and others to verify compliance with the chosen approach and protect ethically compliant stakeholders from being unfairly exploited by unethical behaviour of others. (shrink)

Psychiatry is rapidly adopting digital phenotyping and artificial intelligence/machine learning tools to study mental illness based on tracking participants’ locations, online activity, phone and text message usage, heart rate, sleep, physical activity, and more. Existing ethical frameworks for return of individual research results (IRRs) are inadequate to guide researchers for when, if, and how to return this unprecedented number of potentially sensitive results about each participant’s real-world behavior. To address this gap, we convened an interdisciplinary expert working group, supported by (...) a National Institute of Mental Health grant. Building on established guidelines and the emerging norm of returning results in participant-centered research, we present a novel framework specific to the ethical, legal, and social implications of returning IRRs in digital phenotyping research. Our framework offers researchers, clinicians, and Institutional Review Boards (IRBs) urgently needed guidance, and the principles developed here in the context of psychiatry will be readily adaptable to other therapeutic areas. (shrink)

COVID-19 vaccines are likely to be scarce for years to come. Many countries, from India to the U.K., have demonstrated vaccine nationalism. What are the ethical limits to this vaccine nationalism? Neither extreme nationalism nor extreme cosmopolitanism is ethically justifiable. Instead, we propose the fair priority for residents framework, in which governments can retain COVID-19 vaccine doses for their residents only to the extent that they are needed to maintain a noncrisis level of mortality while they are implementing reasonable public (...) health interventions. Practically, a noncrisis level of mortality is that experienced during a bad influenza season, which society considers an acceptable background risk. Governments take action to limit mortality from influenza, but there is no emergency that includes severe lockdowns. This “flu-risk standard” is a nonarbitrary and generally accepted heuristic. Mortality above the flu-risk standard justifies greater governmental interventions, including retaining vaccines for a country's own citizens over global need. The precise level of vaccination needed to meet the flu-risk standard will depend upon empirical factors related to the pandemic. This links the ethical principles to the scientific data emerging from the emergency. Thus, the FPR framework recognizes that governments should prioritize procuring vaccines for their country when doing so is necessary to reduce mortality to noncrisis flu-like levels. But after that, a government is obligated to do its part to share vaccines to reduce risks of mortality for people in other countries. We consider and reject objections to the FPR framework based on a country: having developed a vaccine, raising taxes to pay for vaccine research and purchase, wanting to eliminate economic and social burdens, and being ineffective in combating COVID-19 through public health interventions. (shrink)

Although death by neurologic criteria is legally recognized throughout the United States, state laws and clinical practice vary concerning three key issues: the medical standards used to determine death by neurologic criteria, management of family objections before determination of death by neurologic criteria, and management of religious objections to declaration of death by neurologic criteria. The American Academy of Neurology and other medical stakeholder organizations involved in the determination of death by neurologic criteria have undertaken concerted action to address variation (...) in clinical practice in order to ensure the integrity of brain death determination. To complement this effort, state policymakers must revise legislation on the use of neurologic criteria to declare death. We review the legal history and current laws regarding neurologic criteria to declare death and offer proposed revisions to the Uniform Determination of Death Act and the rationale for these recommendations. (shrink)

1 Evidence-based policy requires researchers to provide the answers to ecological questions that are of interest to policy makers. To find out what those questions are in the UK, representatives from 28 organizations involved in policy, together with scientists from 10 academic institutions, were asked to generate a list of questions from their organizations. 2 During a 2-day workshop the initial list of 1003 questions generated from consulting at least 654 policy makers and academics was used as a basis for (...) generating a short list of 100 questions of significant policy relevance. Short-listing was decided on the basis of the preferences of the representatives from the policy-led organizations. 3 The areas covered included most major issues of environmental concern in the UK, including agriculture, marine fisheries, climate change, ecosystem function and land management. 4 The most striking outcome was the preference for general questions rather than narrow ones. The reason is that policy is driven by broad issues rather than specific ones. In contrast, scientists are frequently best equipped to answer specific questions. This means that it may be necessary to extract the underpinning specific question before researchers can proceed. 5 Synthesis and applications. Greater communication between policy makers and scientists is required in order to ensure that applied ecologists are dealing with issues in a way that can feed into policy. It is particularly important that applied ecologists emphasize the generic value of their work wherever possible. (shrink)

Motivation has been the subject of much research in the sport psychology literature, whereas athlete mental health has received limited attention. Motivational complexities in elite sport are somewhat reflected in the mental health literature, where there is evidence for both protective and risk factors for athletes. Notably, few studies have linked motivation to mental health. Therefore, the key objective of this study was to test four mental health outcomes in the motivational sequence posited by the Hierarchical Model of Intrinsic and (...) Extrinsic Motivation: motivational climate  basic psychological needs  motivation  mental health outcomes. Elite team-sport athletes (140 females, 75 males) completed seven psychometric inventories of motivation-related and mental health variables. Overall, the athletes reported positive motivational patterns, with autonomous motivation and task climate being more prevalent than their less adaptive counterparts. Elevated depressive symptoms and poor sleep quality affected nearly half of the cohort. Structural equation modelling supported pathways between motivational climate, basic needs, motivation, and mood, depressive symptoms, sleep quality, and trait anxiety. Specifically, a task climate was positively associated with the three basic psychological needs, and an ego climate was positively associated with competence. Autonomy and relatedness had positive and negative associations with autonomous and controlled forms of motivation, respectively. Controlled motivation regulations were positively associated with the four mental health outcomes. Integrated regulation had a negative association with anxiety, and intrinsic regulation had a positive association with depressive symptoms. These findings highlight the complexities of and interrelations between motivation and mental health among athletes, and support the importance of considering mental health as an outcome of motivation. (shrink)