Small tandem DNA duplications in the range of 15 to 300 base‐pairs play an important role in the aetiology of human disease and contribute to genome diversity. Here, we discuss different proposed mechanisms for their occurrence and argue that this type of structural variation mainly results from mutagenic repair of chromosomal breaks. This hypothesis is supported by both bioinformatical analysis of insertions occurring in the genome of different species and disease alleles, as well as by CRISPR/Cas9‐based experimental data from different (...) model systems. Recent work points to fill‐in synthesis at double‐stranded DNA breaks with complementary sequences, regulated by end‐joining mechanisms, to account for small tandem duplications. We will review the prevalence of small tandem duplications in the population, and we will speculate on the potential sources of DNA damage that could give rise to this mutational signature. With the development of novel algorithms to analyse sequencing data, small tandem duplications are now more frequently detected in the human genome and identified as oncogenic gain‐of‐function mutations. Understanding their origin could lead to optimized treatment regimens to prevent therapy‐induced activation of oncogenes and might expose novel vulnerabilities in cancer. (shrink)

This article presents the results of a qualitative study on the ethical aspects of inclusion practice for radiotherapy patients taking part in clinical research. The study focused on the standards and values of this process. Patients and physicians were interviewed about their views and experiences. Analysis of these interviews showed that candidate research participants need better protection from unwanted factors that could influence their choice about participation. Researchers need proper education about regulation, codes and directives in the field of research (...) ethics, and they should be aware of the underlying ethical concepts of these regulations. A sound institutional ethics policy is necessary in order to guide medical staff in decisions about the inclusion of patients in trials. (shrink)

This paper concludes a special feature of Sustainability Science that explores a broad range of social value theoretical traditions, such as religious studies, social psychology, indigenous knowledge, economics, sociology, and philosophy. We introduce a novel transdisciplinary conceptual framework that revolves around concepts of 'lenses' and 'tensions' to help navigate value diversity. First, we consider the notion of lenses: perspectives on value and valuation along diverse dimensions that describe what values focus on, how their sociality is envisioned, and what epistemic and (...) procedural assumptions are made. We characterise fourteen of such dimensions. This provides a foundation for exploration of seven areas of tension, between: (1) the values of individuals vs collectives; (2) values as discrete and held vs embedded and constructed; (3) value as static or changeable; (4) valuation as descriptive vs normative and transformative; (5) social vs relational values; (6) different rationalities and their relation to value integration; (7) degrees of acknowledgment of the role of power in navigating value conflicts. In doing so, we embrace the 'mess' of diversity, yet also provide a framework to organise this mess and support and encourage active transdisciplinary collaboration. We identify key research areas where such collaborations can be harnessed for sustainability transformation. Here it is crucial to understand how certain social value lenses are privileged over others and build capacity in decision-making for understanding and drawing on multiple value, epistemic and procedural lenses. (shrink)

This paper concludes a special feature of Sustainability Science that explores a broad range of social value theoretical traditions, such as religious studies, social psychology, indigenous knowledge, economics, sociology, and philosophy. We introduce a novel transdisciplinary conceptual framework that revolves around concepts of ‘lenses’ and ‘tensions’ to help navigate value diversity. First, we consider the notion of lenses: perspectives on value and valuation along diverse dimensions that describe what values focus on, how their sociality is envisioned, and what epistemic and (...) procedural assumptions are made. We characterise fourteen of such dimensions. This provides a foundation for exploration of seven areas of tension, between: (1) the values of individuals vs collectives; (2) values as discrete and held vs embedded and constructed; (3) value as static or changeable; (4) valuation as descriptive vs normative and transformative; (5) social vs relational values; (6) different rationalities and their relation to value integration; (7) degrees of acknowledgment of the role of power in navigating value conflicts. In doing so, we embrace the ‘mess’ of diversity, yet also provide a framework to organise this mess and support and encourage active transdisciplinary collaboration. We identify key research areas where such collaborations can be harnessed for sustainability transformation. Here it is crucial to understand how certain social value lenses are privileged over others and build capacity in decision-making for understanding and drawing on multiple value, epistemic and procedural lenses. (shrink)

The medical profession is observing a rising number of calls to action considering the threat that climate change poses to global human health. Theory-led bioethical analyses of the scope and weight of physicians’ normative duty towards climate protection and its conflict with individual patient care are currently scarce. This article offers an analysis of the normative issues at stake by using Korsgaard’s neo-Kantian moral account of practical identities. We begin by showing the case of physicians’ duty to climate protection, before (...) we succinctly introduce Korsgaard’s account. We subsequently show how the duty to climate protection can follow from physicians’ identity of being a healthcare professional. We structure conflicts between individual patient care and climate protection, and show how a transformation in physicians’ professional ethos is possible and what mechanisms could be used for doing so. An important limit of our analysis is that we mainly address the level of individual physicians and their practical identities, leaving out important measures to respond to climate change at the mesolevels and macrolevels of healthcare institutions and systems, respectively. (shrink)

BACKGROUND: Delusions in schizophrenia are commonly approached as empirical false beliefs about everyday reality. Phenomenological accounts, by contrast, have suggested that delusions are more adequately understood as pertaining to a different kind of reality experience. How this alteration of reality experience should be characterised, which dimensions of experiential life are involved, and whether delusional reality might differ from standard reality in various ways is unclear and little is known about how patients with delusions value and relate to these experiential alterations. (...) This study aimed to investigate the nature of delusional reality experience, and its subjective apprehension, in individuals with lived experience of delusions and a schizophrenia-spectrum diagnosis. METHODS: In this qualitative phenomenological study, we recruited individuals with lived experience of delusions and a schizophrenia-spectrum diagnosis from two psychiatric-hospital services in Belgium using homogenous sampling. Criteria for participation were having undergone at least one psychotic episode with occurring delusional symptoms, present at least 1 year before participation, on the basis of clinical notes assessed by the attending psychiatrist; a schizophrenia-spectrum diagnosis, ascertained through clinical interview by the attending psychiatrist upon admission; being aged between 18 years and 65 years; and having the capacity to give informed consent. Exclusion criteria included worries concerning capacity to consent and risk of distress caused by participation. We did phenomenologically driven semi-structured interviews with the participants to explore the nature of delusional reality experience and their subjective valuation of these experiences. We used interpretative phenomenological analysis, a qualitative method tailored to the in-depth exploration of participants’ first-person perspective, to analyse their accounts. FINDINGS: Between March 2, 2020, and Sept 30, 2020, 18 adults participated in the interview study. The findings suggest that delusions are often embedded in wide-ranging alterations of basic reality experience, involving quasi-ineffable atmospheric and ontological qualities that undermine participants’ sense of the world as unambiguously real, fully present, and shared with others. We also found that delusional reality experience can differ from standard reality in various ways, across multiple dimensions, and that participants are often implicitly or explicitly aware of the distinction between delusional and standard reality. Delusional experience can have an enduring value and meaning that is not fully captured by a strictly medical perspective. INTERPRETATION: Increased awareness and recognition of the distinctive nature of delusional reality experience, in both clinical and research settings, can improve diagnostic accuracy, explanatory models, and therapeutic support for individuals with delusions whose lived realities are not always evident from an everyday perspective. FUNDING: FWO Flanders. TRANSLATION: For the Dutch translation of the abstract see Supplementary Materials section. (shrink)

We are extremely grateful for the insightful and thought-provoking commentaries on our feature article.1 We have distilled four themes emerging from the commentaries, and we would also like to address one misunderstanding of our argument that has appeared. In our article, we explicitly acknowledge that major decisions relevant for climate protection take place at the mesolevels and macrolevels of healthcare, a point raised again in some of the commentaries.2–4 Climate protection is a societal issue, and we thank these authors for (...) the concrete proposals of potential models to guide action. Yet, to us, it still makes sense to reflect simultaneously on the responsibilities that physicians have themselves. Without wanting to put the main responsibility on them, we argue it is important to start thinking about the scope of action that physicians actually have (or not have). As we have argued the need for climate action comes ever more into focus of society, we wanted to explore whether the professional ethics of the medical professionals needs to be amended. Our argument is that this is the case, based on the reasons that climate change has a big health impact while simultaneously the health system has a strong climate impact. Based on the World Medical Association (WMA) Declaration of Geneva the focus on the individual patient is clear, but this and other important codices do also include a public health perspective. The (model) Professional Code for Physicians in Germany, for example, states in its first article that ‘Physicians serve the health of …. (shrink)

Over the past years, the intersubjective dimension of psychotic disorders, including schizophrenia, has gained increasing phenomenological attention. Psychopathologists and philosophers have developed ideas on how the social aspects of psychotic symptoms and experiences could be understood, in particular in their relation to the ipseity disturbance model, namely the idea that schizophrenia is essentially a disorder of the minimal self. Although the exact characteristics of the ipseity disorder hypothesis can differ from author to author, emphasizing certain phenomenological aspects like temporality or (...) embodiment... (shrink)

Situated normativity is the ability of skilled individuals to distinguish better from worse, adequate from inadequate, appropriate from inappropriate, or correct from incorrect in the context of a particular situation. Situated normativity consists in a situated appreciation expressed in normative behaviour, and can be experienced as a bodily affective tension that motivates a skilled individual to act on particular possibilities for action offered by a concrete situation. The concept of situated normativity has so far primarily been discussed in the context (...) of skilled unreflective action. In this paper, we aim to explore and sketch the role of the concept of situated normativity in characterising more reflective forms of normativity. The goal of the paper is two-fold: first, by showing more reflective forms of normativity to be continuous with unreflective situated normativity, we bring these reflective forms into the reach of embodied accounts of cognition; and second, by extending the concept of situated normativity, new light is thrown on questions regarding reflective forms of cognition. We show that sociomaterial aspects of situations are crucial for understanding more reflective forms of normativity. We also shed light on the important question of how explicit rules can compel people to behave in particular ways. (shrink)

The Radical Enactive/embodied view of Cognition, or REC, claims that all cognition is a matter of skilled performance. Yet REC also makes a distinction between basic and content-involving cognition, arguing that the development of basic to content-involving cognition involves a kink. It might seem that this distinction leads to problematic gaps in REC’s story. We address two such alleged gaps in this paper. First, we identify and reply to the concern that REC leads to an “interface problem”, according to which (...) REC has to account for the interaction of two minds co-present in the same cognitive activity. We emphasise how REC’s view of content-involving cognition in terms of activities that require particular sociocultural practices can resolve these interface concerns. The second potential problematic gap is that REC creates an unjustified difference in kind between animal and human cognition. In response, we clarify and further explicate REC’s notion of content, and argue that this notion allows REC to justifiably mark the distinction between basic and content-involving cognition as a difference in kind. We conclude by pointing out in what sense basic and content-involving cognitive activities are the same, yet different. They are the same because they are all forms of skilled performance, yet different as some forms of skilled performance are genuinely different from other forms. (shrink)

In this paper, I develop an ecological-enactive perspective on the role rules play in linguistic behaviour. I formulate and motivate the hypothesis that metalinguistic reflexivity – our ability to talk about talking – is constitutive of linguistic normativity. On first sight, this hypothesis might seem to fall prey to a regress objection. By discussing the work of Searle, I show that this regress objection originates in the idea that learning language involves learning to follow rules from the very start. I (...) propose an ecological-enactive response to the regress objection. The key move is to deny that language learning consists initially in learning rules. A child first engages in regular communicative behaviour, by learning first-order linguistic skills, and then retroactively interprets her own behaviour in normative metalinguistic terms, i.e., as being guided by rules by relying on reflexive or second-order linguistic skills. On this view, metalinguistic reflexivity enables regulation of already regular communicative behaviour, and thereby constitutes linguistic normativity. Finally, I argue that linguistic rules are resources: they are available to participants in order to (re)negotiate properties of situated language behaviour and thereby reorganize linguistic practices. The account developed in this paper thus allows us to understand the constitutive role of metalinguistic reflexivity for linguistic normativity without falling prey to the regress objection. (shrink)

Physicians frequently encounter situations in which their professional practice is intermingled with moral affordances stemming from other domains of the physician’s lifeworld, such as family and friends, or from general morality pertaining to all humans. This article offers a typology of moral conflicts ‘at the margins of professionalism’ as well as a new theoretical framework for dealing with them. We start out by arguing that established theories of professional ethics do not offer sufficient guidance in situations where professional ethics overlaps (...) with moral duties of other origins. Therefore, we introduce the moral theory developed by Christine M. Korsgaard, that centres around the concept of practical identity. We show how Korsgaard’s account offers a framework for interpreting different types of moral conflicts ‘at the margins of professionalism’ to provide either orientation for solving the conflict or an explanation for the emotional and moral burden involved in moral dilemmas. (shrink)

This paper proposes an account of linguistic knowledge in terms of knowing-how, starting from Love's seminal distinction between first-order linguistic activity and second-order (or metalinguistic) practices. Metalinguistic practices are argued to be constitutive of linguistic knowledge. Skilful linguistic behaviour is subject to correction based on criterial support provided through metalinguistic practices. Linguistic know-how is knowing-how to provide and to recognise criterial support for first-order linguistic activity. I conclude that participation in first-order linguistic activity requires a critical reflective attitude, which implies (...) that all first-order linguistic activity has a second-order dimension. -/- . (shrink)

Is materialism right to claim that the world of everyday-life experience – the phenomenal world – is nothing but an illusion produced in physical reality, notably in the brain? Or is Merleau-Ponty right when he defends the fundamental character of the phenomenal world while rejecting physical realism? I address these questions by exploring the nature of the body proper in Merleau-Ponty and Plessner, arguing that physical and phenomenal realism are not mutually exclusive but complementary. The argument includes a close examination (...) of the relationships between scientific and pre-scientific perspectives, between living and non-living things, and between humans and animals. (shrink)

Bennett and Hacker criticize a number of neuroscientists and philosophers for attributing capacities which belong to the human being as a whole, like perceiving or deciding, to a “part” of the human being, viz. the brain. They call this type of mistake the “mereological fallacy”. Interestingly, the authors say that these capacities cannot be ascribed to the mind either. They reject not only materialistic monism but also Cartesian dualism, arguing that many predicates describing human life do not refer to physical (...) or mental properties, nor to the sum of such properties. I agree with this important principle and with the critique of the mereological fallacy which it underpins, but I have two objections to the authors’ view. Firstly, I think that the brain is not literally a part of the human being, as suggested. Secondly, Bennett and Hacker do not offer an account of body and mind which explains in a systematic way how the domain of phenomena which transcends the mental and the physical relates to the mental and the physical. I first argue that Helmuth Plessner’s philosophical anthropology provides the kind of account we need. Then, drawing on Plessner, I present an alternative view of the mereological relationships between brain and human being. My criticism does not undercut Bennett and Hacker’s diagnosis of the mereological fallacy but rather gives it a more solid philosophical–anthropological foundation. (shrink)

The severe hereditary progeroid disorder Cockayne syndrome is a consequence of a defective transcription‐coupled repair (TCR) pathway. This special mode of DNA repair aids a RNA polymerase that is stalled by a DNA lesion in the template and ensures efficient DNA repair to permit resumption of transcription and prevent cell death. Although some key players in TCR, such as the Cockayne syndrome A (CSA) and B (CSB) proteins have been identified, the exact molecular mechanism still remains illusive. A recent report (...) provides new unexpected insights into TCR in yeast.1 The identification and characterisation of a novel protein co‐purifying with the yeast homologue of CSB (Rad26) imposes reassessment of our current understanding of TCR in yeast. What about humans? BioEssays 24:780–784, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

The concept of affordances is rapidly gaining traction in the philosophy of mind and cognitive sciences. Affordances are opportunities for action provided by the environment. An important open question is whether affordances can be used to explain mental action such as attention, counting, and imagination. In this paper, we critically discuss McClelland’s (‘The Mental Affordance Hypothesis’, 2020, Mind, 129(514), pp. 401–427) mental affordance hypothesis. While we agree that the affordance concept can be fruitfully employed to explain mental action, we argue (...) that McClelland’s mental affordance hypothesis contain remnants of a Cartesian understanding of the mind. By discussing the theoretical framework of the affordance competition hypothesis, we sketch an alternative research program based on the principles of embodied cognition that evades the Cartesian worries. We show how paradigmatic mental acts, such as imagination, counting, and arithmetic, are dependent on sensorimotor interaction with an affording environment. Rather than make a clear distinction between bodily and mental action, the mental affordances highlight the embodied nature of our mental action. We think that in developing our alternative research program on mental affordances, we can maintain many of the excellent insights of McClelland’s account without reintroducing the very distinctions that affordances were supposed to overcome. (shrink)

Background: The classical symptom specificity hypothesis (Blatt, 1974) links obsessional symptoms to autonomous interpersonal behavior. Inconsistent findings from cross-sectional group studies on symptom specificity have previously been associated with several conceptual and methodological limitations intrinsic to nomothetic research. Previous empirical case research reported ambivalences between autonomous and dependent interpersonal behavior in obsessional pathology. Aim and Method: The present ‘theory-building’ case study specifically aims at further refinement of the classical symptom specificity hypothesis by testing specific operationalizations within an empirical single case (...) design. Consensual Qualitative Research for Case studies is used to quantitatively and qualitatively describe the longitudinal, clinical interplay between obsessional symptoms and interpersonal dynamics throughout the process of a psychodynamic therapy. Interpersonal functioning is assessed by means of the Core Conflictual Relationship Theme method. The classical symptom specificity hypothesis is contrasted to an alternative hypothesis of interpersonal ambivalences as determinants of obsessional symptoms. Results: Close associations between obsessions and interpersonal dynamics are observed. Findings predominantly affirm the ambivalence hypothesis rather than the classical symptom specificity hypothesis. Psychodynamic interventions focusing on interpersonal conflicts are related to symptomatic changes. Conceptual and methodological considerations, limitations and future research indications are discussed. (shrink)

Is materialism right to claim that the world of everyday-life experience – the phenomenal world – is nothing but an illusion produced in physical reality, notably in the brain? Or is Merleau-Ponty right when he defends the fundamental character of the phenomenal world while rejecting physical realism? I address these questions by exploring the nature of the body proper in Merleau-Ponty and Plessner, arguing that physical and phenomenal realism are not mutually exclusive but complementary. The argument includes a close examination (...) of the relationships between scientific and pre-scientific perspectives, between living and non-living things, and between humans and animals. (shrink)

In depicting five “spheres of morality” occupied by physicians Doernberg and Troug provide an impressive analysis on physicians’ various commitments and role conflicts which are excellently illustr...

Is materialism right to claim that the world of everyday-life experience - the phenomenal world - is nothing but an illusion produced in physical reality, notably in the brain? Or is Merleau-Ponty right when he defends the fundamental character of the phenomenal world while rejecting physical realism? Jasper van Buuren addresses these questions by exploring the nature of the body proper in Merleau-Ponty and Plessner, arguing that physical and phenomenal realism are not mutually exclusive but complementary. The argument includes (...) a close examination of the relationships between scientific and pre-scientific perspectives, between living and non-living things, and between humans and animals. (shrink)

In 2017, the blockade of Qatar Gulf states caused a plethora of effects on the country. This paper sought to examine the resulting threat effects of this blockade in terms of lowered self-esteem and well-being, and the potential buffering effects of an overarching identity. Using self-report questionnaire data from Qatari secondary school students, multiple moderated mediation models investigated the predictive effects of youngsters’ perceived threat, via self-esteem, on their well-being, and the mitigating roles herein of, respectively, national, Gulf region, and (...) Arab identity. Perceived threat was indeed related to lower well-being via lower self-esteem, and this relationship was equally strong for those low and high in social identity. In terms of the three facets of identity, the overarching Gulf identity seems the most predictive, and it even buffers the negative relationship between threat and reduced self-esteem. (shrink)

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This paper proposes a framework for understanding and analysing online social resistance movements based on Hilde Lindemann’s concept of counterstories (Damaged Identities, Narrative Repair, 2003). This framework is based on the premise that we shape our identities in shared social spaces, and that such shared spaces are structured according to so-called ‘master narratives’. Master narratives define the ‘realm of possible identities’ that we can assume, and form the basis for either recognizing or denying recognition to various social groups in specific (...) roles that they might occupy. Social oppression occurs when master narratives preclude or forbid a certain form of self-expression, or alternatively force members of a specific social group into a determinate societal role (say, women who receive recognition only in the roles of mother or housewife). Counterstories serve as a corrective to these aspects of oppression by challenging the oppressive facets of master narratives. Based on this framework, I propose an interpretation of the #MeToo movement as a counterstory that aims to change the oppressive aspects of the patriarchal master narrative that (partially) structures many shared social spaces in the modern Western world. I end this paper by applying the framework to consider potential obstacles #MeToo may encounter as a distinctively online movement. (shrink)

Harry G. Frankfurt has put the problem of volitional conflict at the center of philosophical attention. If you care fundamentally about your career and your family, but these cares conflict, this conflict undermines the coherency of your decision standard and thereby your ability to choose and act autonomously. The standard response to this problem is to argue that you can overcome volitional conflict by unifying your foundational motivational states. As Frankfurt puts it, the ‘totality of things that an agent cares (...) about’ plus his ‘ordering of how important to him they are effectively specifies his answer to the question of how to live’ (The Reasons of Love(Princeton: Princeton University Press, 2004), p. 23). In this paper, I critically assess the three main reasons given for such a coherency requirement: 1) we can do only one action at a time; 2) our motivational states come with normative pressure towards coherency; and 3) conflicting motivational states provide us with an incoherent decision-making framework. I conclude that these reasons do not ground a coherency requirement for practical deliberation and argue that we can autonomously express ourselves as volitionally conflicted by acting on our conflicting motivational states over the course of multiple actions. (shrink)