I. EXECUTIVE SUMMARY The MRCT Center Post-trial Responsibilities: Continued Access to an Investigational Medicine Framework outlines a case-based, principled, stakeholder approach to evaluate and guide ethical responsibilities to provide continued access to an investigational medicine at the conclusion of a patient’s participation in a clinical trial. The Post-trial Responsibilities (PTR) Framework includes this Guidance Document as well as the accompanying Toolkit. A 41-member international multi-stakeholder Workgroup convened by the Multi-Regional Clinical Trials Center of Brigham and Women’s Hospital and Harvard University (...) (MRCT Center) developed this Guidance and Toolkit. Project Motivation A number of international organizations have discussed the responsibilities stakeholders have to provide continued access to investigational medicines. The World Medical Association, for example, addressed post-trial access to medicines in Paragraph 34 of the Declaration of Helsinki (WMA, 2013): “In advance of a clinical trial, sponsors, researchers and host country governments should make provisions for post-trial access for all participants who still need an intervention identified as beneficial in the trial. This information must also be disclosed to participants during the informed consent process.” This paragraph and other international guidance documents converge on several consensus points: • Post-trial access (hereafter referred to as “continued access” in this Framework [for terminology clarification – see definitions]) is the responsibility of sponsors, researchers, and host country governments; • The plan for continued access should be determined before the trial begins, and before any individual gives their informed consent; • The protocol should delineate continued access plans; and • The plan should be transparent to potential participants and explained during the informed consent process. -/- However, there is no guidance on how to fulfill these responsibilities (i.e., linking specific responsibilities with specific stakeholders, conditions, and duration). To fill this gap, the MRCT Center convened a working group in September of 2014 to develop a framework to guide stakeholders with identified responsibilities. This resultant Framework sets forth applicable principles, approaches, recommendations and ethical rationales for PTR regarding continued access to investigational medicines for research participants. (shrink)

Our understanding of biological processes in humans is often based on examination of analogous processes in other organisms. The nematode worm Caenorhabditis elegans has been a particularly valuable model, leading to Nobel prize winning discoveries in development and genetics. Until recently, however, the worm has not been widely used as a model to study transcription due to the lack of a comprehensive catalogue of its RNA transcripts. A recent study by Chen et al. uses next‐generation sequencing to address this issue, (...) mapping the transcription initiation sites in C. elegans and finding many unexpected similarities between the transcription of enhancers and promoters in the worm and mammalian genomes. As well as providing a valuable resource for researchers in the C. elegans community, these findings raise the possibility of using the worm as a model to investigate some key, current questions about transcriptional regulation that remain technically challenging in more complex organisms. (shrink)

Negative people/wildlife interaction has raised public interest in wildlife population control. We present a contingent valuation study of alternative deer control measures considered for Hilton Head Island, SC. Lethal control usig sharpshooters and nonlethal immuno-contraception techniques are evaluated. A mail-back survey was used to collect resident willingness-to-pay information for reduced deer densities and consequent property damage. Residents are unwilling to spend more for the nonlethal alternative. The estimated WTP appears theoretically consistent as increasing levels of abatement for both lethal and (...) nonlethal alternatives demonstrate diminishing marginal benefits. Over 60% of respondents bid zero regardless of control measure, suggesting a referendum would fail. However, only half of these zero bidders expressed no problem with deer, while the other half bid zero because of distaste for the control alternative, safety concerns, or doubt about effectiveness. Inclusion of these responses as legitimate zero bids depressed mean WTP estimates from 22 to 31%. (shrink)

The extensive literature on the Learning Organisation proposes that a competitive advantage can be achieved through the systematised generation and application of knowledge. Consequently, much of the debate concerns the processes, routines and organisational features that a firm should adopt to learn more, and faster, than its competitors. Less attention is given to understanding the nature of the knowledge that is created by these Learning Organisations. We hold that the topic is more important than its current weight in the literature (...) because the performance claims of the models proposed critically depend upon the newly acquired knowledge replacing ignorance or knowledge with less utility. In this paper we explore the nature of knowledge that Learning Organisation theory seeks to create by articulating implicit epistemological assumptions found within the literature. We show that the capacities of each epistemology to help an organisation reject falsehood and make greater use of its knowledge are critically undermined by these very routines. The paper concludes by highlighting the importance of a sceptical epistemology and outlines a process that would strengthen doubting behaviour. (shrink)

This article relates the emergence of a group of faculty researchers utilizing complexity science approaches. The narrative emerges from three projects combining research into complexity, communities, and technologies. Details of how the research was initiated, and the nature and quality of the conversational method, are provided. In addition, theoretical concepts that were consciously applied and others that arose through insights from the data as it was collected are discussed. Although this is like most real narratives, a never-ending story, it concludes (...) with a presentation of some of the ideas that separate complexity-informed research from other paradigms. (shrink)

Higher education is starting to embrace its role in promoting student wellbeing and life skills, especially given the concerning levels of poor mental health and uncertainties in the future job market. Yet, many of the published studies evaluating positive educational teaching methods thus far are limited to interventions delivered to small student cohorts and/or imbedded within elective wellbeing courses, and are focussed on developed Western countries. This study addressed this gap by investigating the effectiveness of an institution-wide compulsory course informed (...) by the principles of Seligman’s Wellbeing Theory. The course was delivered at a British university in a developing country in Southeast Asia. It purposefully sought to nurture growth-oriented outcomes and was taken by an entire cohort of year one undergraduate students. We tested the effectiveness of the curriculum content and staff coaching style in achieving life skills, and evaluated how these perceptions influenced students’ subjective wellbeing. A convergent mixed-methods design was used with 350 survey respondents and 11 interviewees. Perceived life skills scores showed a 2.5% improvement at the end of the course. Partial Least Squares Structural Equation Modelling tested the predicted relationships between variables. All relationships were statistically significant, but the influence of course design and educators’ style on life skills acquisition was moderate, while the effect on subjective happiness and life satisfaction was very weak. Qualitative data indicated that while quantifiable benefits to wellbeing might not be immediate, students did anticipate longer-term benefits for happiness and life satisfaction. This finding suggests that such a novel educational approach is well-received by Asian students and may sow the seeds for future benefit by positively impacting on their skills, behaviours, attitudes, and values. To achieve optimal flourishing at university, we recommend exploring teaching practises that combine positive education with coaching psychology practises. (shrink)

The seventeenth century was a period of extraordinary invention, discovery and revolutions in scientific, social and political orders. It was a time of expansive automation, biological discovery, rapid advances in medical knowledge, of animal trials and a questioning of the boundaries between species, human and non-human, between social classes, and of the assumed naturalness of political inequality. This book gives a tour through those objects, ordinary and extraordinary, which captivated the philosophical imagination of the single most important French philosopher of (...) this period, Rene Descartes. Deborah J. Brown and Calvin G. Normore document Descartes' attempt to make sense of the complex, composite objects of human and divine invention, consistent with the fundamental tenets of his metaphysical system. Their central argument is that, far from reducing all the categories of ordinary experience to the two basic categories of substance, mind and body, Descartes' philosophy recognises irreducible composites that resist reduction, and require their own distinctive modes of explanation. (shrink)

Descartes is often accused of having fragmented the human being into two independent substances, mind and body, with no clear strategy for explaining the apparent unity of human experience. Deborah Brown argues that, contrary to this view, Descartes did in fact have a conception of a single, integrated human being, and that in his view this conception is crucial to the success of human beings as rational and moral agents and as practitioners of science. The passions are pivotal in (...) this, and in a rich and wide-ranging discussion she examines Descartes' place in the tradition of thought about the passions, the metaphysics of actions and passions, sensory representation, and Descartes' account of self-mastery and virtue. Her study is an important and original reading not only of Descartes' account of mind-body unity but also of his theory of mind. (shrink)

Absence of evidence arguments are indispensable to comparative neurobiology. The absence in a given species of a homologous neural architecture strongly correlated with a type of conscious experience in humans should be able to be taken as a prima facie reason for concluding that the species in question does not have the capacity for that conscious experience. Absence of evidence reasoning is, however, widely disparaged for being both logically illicit and unscientific. This paper argues that these concerns are unwarranted. There (...) is no logical barrier to formulating cogent absence of evidence arguments; indeed, accepting such arguments is part of what it is to be committed to falsifiability as a critical aspect of the scientific method. Absence of evidence arguments can always be blocked, however, by assuming that psychological properties are ‘multiply realizable’. While we take multiple realizability to be highly likely at some level of analysis, we argue that it is question-begging to assume that it exists at every level of analysis, and thus it should not automatically be thought to undermine absence of evidence reasoning in the animal consciousness debate. Using the example of pain and focusing on homologies at the level of information processing tasks, we show how, in the science of consciousness, an absence of evidence might well serve as evidence of absence. (shrink)

Despite eschewing the utility of ends or purposes in natural philosophy, Descartes frequently engages in functional explanation, which many have assumed is an essentially teleological form of explanation. This article considers the consistency of Descartes's appeal to natural functions, advancing the idea that he is utilizing a non-normative, non-teleological form of functional explanation. It will be argued that Cartesian functional analysis resembles modern causal functional analysis, and yet, by emphasizing the interdependency of parts of biological systems, is able to avoid (...) many of the problems attendant upon modern causal theories. It is for this reason, if no other, that the study of Descartes's natural philosophy should be of interest to contemporary theorists of functional analysis. (shrink)

There is a tension within Ockham's theory of mental language between its claim to being a semantics for conventional languages and its claim to being a model of concept acquisition and thought. In particular, the commitment to a redundancy-free mental language which serves to explain important semantic relations such as synonymy and ambiguity conflicts, _prima facie, with the possibility of opaque belief contexts. I argue that it is preferable to treat the theory of mental language as an idealized theory of (...) cognitive competence than to forfeit, as Jerry Fodor does, the commitment to conceptual parsimony. (shrink)

This article presents the Pilgrimage Model as a template for educators wishing to lead students on site-specific studies of engaged learning. During the 2015–2016 academic year, a group of Georgeto...

BackgroundChildhood abuse increases risk for high levels of distress in response to future stressors. Interpersonal social support is protective for health, particularly during stress, and may be particularly beneficial for individuals who experienced childhood abuse.ObjectiveInvestigate whether childhood abuse predicts levels of posttraumatic stress disorder (PTSD) symptoms related to the COVID-19 pandemic, and test whether the perceived availability of social companionship preceding the pandemic moderates this relationship.MethodsDuring Phase 1, adults (N= 120; AgeM[SD] = 19.4 [0.94]) completed a retrospective measure of childhood (...) adversity along with a measure of perceived availability of opportunities for social engagement immediately preceding the pandemic. Two weeks after the COVID-19 pandemic declaration, participants completed the Impact of Event Scale-Revised (IES-R) with respect to the pandemic. Hierarchical linear regression analyses examined the interaction between childhood abuse and the perceived availability of social companionship preceding the pandemic as a predictor of PTSD symptoms.ResultsAdjusting for covariates, the interaction between childhood abuse and perceived availability of others to engage with before the onset of the pandemic was a significant predictor of IES-hyperarousal (β = −0.19,t= −2.06,p= 0.04, ΔR2= 0.032, CI: [−0.31 to −0.01]).ConclusionLevels of perceived opportunities for social companionship before the pandemic associates with levels of hyperarousal related to the pandemic, particularly for individuals who experienced high levels of childhood abuse. More research is needed to understand how to mitigate the higher levels of distress related to the pandemic for these individuals in order to reduce risk for future psychiatric disorders. (shrink)

RésuméL'énigme de Hume au sujet de la connaissance de soi repose sur l'idée qu'il n'y a pour l'esprit que deux modes d'accès épistémique à soi-même: le contact direct ou non inférentiel avec le soi, d'une part, et la connaissance indirecte, à base d'inférence, d'autre part. Hume rejette le premier de ces modes enpartant de ceci que nous n'avons dans l'introspection qu'une connaissance des expériences et jamais de la substance mentale, et il rejette le second comme incapable de contrer le scepticisme, (...) sa conclusion étant que ce nous appelons un soi n'est rien d'autre que l'amas des expériences que nous rencontrons. Il y a, cependant, en plus de ces deux modes d'accès, une troisième possibilité, que Hume ne semble jamais prendre en considération, mais qui était caractéristique de l'approche de Thomas d'Aquin à la connaissance de soi, comme de celle de Descartes. Pour ces auteurs, le mode d'accès que l 'esprit a à lui-même est une connaissance indirecte non inférentielle. Le présent article propose ainsi de repenser la façon dont ces philosophes ont conçu la connaissance qu'un individu a de lui-même. En particulier, l'un des aspects de la doctrine de Thomas d'Aquin qui est souvent négligé concerne le rôle que joue dans la connaissance du soi individuel la prise de conscience de l'implication de la volonté dans la pensée. (shrink)

RÉSUMÉ: L'énigme de Hume au sujet de la connaissance de soi repose sur l'idée qu'il n'y a pour l'esprit que deux modes d'accès épistémique à soi-même: le contact direct ou non inférentiel avec le soi, d'une part, et la connaissance indirecte, à base d'inférence, d'autre part. Hume rejette le premier de ces modes en partant de ceci que nous n'avons dans l'introspection qu'une connaissance des expériences et jamais de la substance mentale, et il rejette le second comme incapable de contrer (...) le scepticisme, sa conclusion étant que ce nous appelons un soi n'est rien d'autre que l'amas des expériences que nous rencontrons. Il y a, cependant, en plus de ces deux modes d'accès, une troisième possibilité, que Hume ne semble jamais prendre en considération, mais qui était caractéristique de l'approche de Thomas d'Aquin à la connaissance de soi, comme de celle de Descartes. Pour ces auteurs, le mode d'accès que l'esprit a à lui même est une connaissance indirecte non inférentielle. Le présent article propose ainsi de repenser la façon dont ces philosophes ont conçu la connaissance qu'un individu a de lui-même. En particulier, l'un des aspects de la doctrine de Thomas d'Aquin qui est souvent négligé concerne le rôle que joue dans la connaissance du soi individuel la prise de conscience de l'implication de la volonté dans la pensée. (shrink)

Rehabilitating some of Bakhtin's neglected ideas and reframing him as a philosopher of aesthetics, Bakhtin Reframed will be essential reading for the huge community of Bakhtin scholars as well as students and practitioners of visual culture ...

There are many prominent examples of artists with autism. However, even when confronted with evidence of these accomplished autistic savants, pragmatic aesthetic theories cannot adequately account for the work of these accomplished artists as artists. This article first examines the nature of autism and explores a prominent psychological theory that purports to explain autistic symptoms. This prominent theory, the theory of mind thesis, holds that autistic symptoms are the result of the failure of persons with autism to make certain types (...) of secondorder propositional attitude attributions. Second, the article describes the work of three visual artists with autism. There can be no doubt that these individuals are in fact artists. Third, the article examines pragmatic aesthetic theory and demonstrates why the pragmatic theory fails to adequately account for the accomplishment of autistic artists. The unique psychological deficits that characterize autism present a challenge to pragmatic aesthetic theories in particular. The conclusion is that the pragmatic theory’s inability to accommodate the artist autistic artist is a profound shortcoming. A revision of the pragmatic theory is called for, as is embracing of the development of the special talents of persons with autism. (shrink)

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

It is considered the right of children to have their pain managed effectively. Yet, despite extensive research findings, policy guidelines and practice standard recommendations for the optimal management of paediatric pain, clinical practices remain inadequate. Empirical evidence definitively shows that unrelieved pain in children has only harmful consequences, with no benefits. Contributing factors identified in this undermanaged pain include the significant role of nurses. Nursing attitudes and beliefs about children’s pain experiences, the relationships nurses share with children who are suffering, (...) and knowledge deficits in pain management practices are all shown to impact unresolved pain in children. In this article, a relational ethics perspective is used to explore the need for nurses to engage in authentic relationships with children who are experiencing pain, and to use evidence-based practices to manage that pain in order for this indefensible suffering of children to end. (shrink)