In the conclusion to this multi-part article I first review the discussions carried out around the six essential questions in psychiatric diagnosis – the position taken by Allen Frances on each question, the commentaries on the respective question along with Frances’ responses to the commentaries, and my own view of the multiple discussions. In this review I emphasize that the core question is the first – what is the nature of psychiatric illness – and that in some manner all further (...) questions follow from the first. Following this review I attempt to move the discussion forward, addressing the first question from the perspectives of natural kind analysis and complexity analysis. This reflection leads toward a view of psychiatric disorders – and future nosologies – as far more complex and uncertain than we have imagined. (shrink)

As we go to press, the threat of biological or chemical warfare in the Persian Gulf is no longer imminent. Yet the questions raised by the proposed use of “investigational drugs,” without informed consent, to protect U.S. troops remain. The article by Edmund G. Howe and Edward D. Martin presents the arguments that informed the Pentagon's thinking on the subject. It and the commentaries, by George J. Annas and Michael A. Grodin, and Robert J. Levine, explore, among others, issues (...) of informed consent, of distinguishing ‘research’ and ‘treatment,’ and of the nature and extent of the autonomy of military personnel.—B‐JC, HLN. (shrink)

In face of the multiple controversies surrounding the DSM process in general and the development of DSM-5 in particular, we have organized a discussion around what we consider six essential questions in further work on the DSM. The six questions involve: 1) the nature of a mental disorder; 2) the definition of mental disorder; 3) the issue of whether, in the current state of psychiatric science, DSM-5 should assume a cautious, conservative posture or an assertive, transformative posture; 4) the role (...) of pragmatic considerations in the construction of DSM-5; 5) the issue of utility of the DSM - whether DSM-III and IV have been designed more for clinicians or researchers, and how this conflict should be dealt with in the new manual; and 6) the possibility and advisability, given all the problems with DSM-III and IV, of designing a different diagnostic system. Part I of this article will take up the first two questions. With the first question, invited commentators express a range of opinion regarding the nature of psychiatric disorders, loosely divided into a realist position that the diagnostic categories represent real diseases that we can accurately name and know with our perceptual abilities, a middle, nominalist position that psychiatric disorders do exist in the real world but that our diagnostic categories are constructs that may or may not accurately represent the disorders out there, and finally a purely constructivist position that the diagnostic categories are simply constructs with no evidence of psychiatric disorders in the real world. The second question again offers a range of opinion as to how we should define a mental or psychiatric disorder, including the possibility that we should not try to formulate a definition. The general introduction, as well as the introductions and conclusions for the specific questions, are written by James Phillips, and the responses to commentaries are written by Allen Frances. (shrink)

In face of the multiple controversies surrounding the DSM process in general and the development of DSM-5 in particular, we have organized a discussion around what we consider six essential questions in further work on the DSM. The six questions involve: 1) the nature of a mental disorder; 2) the definition of mental disorder; 3) the issue of whether, in the current state of psychiatric science, DSM-5 should assume a cautious, conservative posture or an assertive, transformative posture; 4) the role (...) of pragmatic considerations in the construction of DSM-5; 5) the issue of utility of the DSM - whether DSM-III and IV have been designed more for clinicians or researchers, and how this conflict should be dealt with in the new manual; and 6) the possibility and advisability, given all the problems with DSM-III and IV, of designing a different diagnostic system. Part I of this article took up the first two questions. Part II will take up the second two questions. Question 3 deals with the question as to whether DSM-V should assume a conservative or assertive posture in making changes from DSM-IV. That question in turn breaks down into discussion of diagnoses that depend on, and aim toward, empirical, scientific validation, and diagnoses that are more value-laden and less amenable to scientific validation. Question 4 takes up the role of pragmatic consideration in a psychiatric nosology, whether the purely empirical considerations need to be tempered by considerations of practical consequence. As in Part 1 of this article, the general introduction, as well as the introductions and conclusions for the specific questions, are written by James Phillips, and the responses to commentaries are written by Allen Frances. (shrink)

While outcomes for children with T-cell acute lymphoblastic leukemia have improved dramatically, survival rates for patients with relapsed/refractory disease remain dismal. Prior studies indicate that glucocorticoid resistance is more common than resistance to other chemotherapies at relapse. In addition, failure to clear peripheral blasts during a prednisone prophase correlates with an elevated risk of relapse in newly diagnosed patients. Here we show that intrinsic GC resistance is present at diagnosis in early thymic precursor T-ALLs as well as in a subset (...) of non-ETP T-ALLs. GC-resistant non-ETP T-ALLs are characterized by strong induction of JAK/STAT signaling in response to interleukin-7 stimulation. Removing IL7 or inhibiting JAK/STAT signaling sensitizes these T-ALLs, and a subset of ETP T-ALLs, to GCs. The combination of the GC dexamethasone and the JAK1/2 inhibitor ruxolitinib altered the balance between pro- and anti-apoptotic factors in samples with IL7-dependent GC resistance, but not in samples with IL7-independent GC resistance. Together, these data suggest that the addition of ruxolitinib or other inhibitors of IL7 receptor/JAK/STAT signaling may enhance the efficacy of GCs in a biologically defined subset of T-ALL.Leukemia advance online publication, 30 May 2017; doi:10.1038/leu.2017.136. (shrink)

Experimental studies have suggested that variables such as aptness or conventionality are predictors of people’s preference for expressing a particular topic–vehicle pair as either a metaphor or a simile. In the present study, we investigated if such variables would also be predictive within a more naturalistic context, where other variables, such as the intention to include an explanation, may also influence people’s decision. Specifically, we investigated the production of metaphor and simile expressions on the Internet via the Google search engine (...) and checked for accompanying explanations, as well as the properties they expressed, to examine whether ratings such as aptness, conventionality, as well as participants’ own stated preference or the intention to produce an explanation, would predict which topic–vehicle pairs appeared more often as metaphor. We found that participants’ stated preference predicted metaphor dominance on the Internet, and that apt topic–vehicles occurred more often as metaphors. The explanations collected, however, occurred 82% of the time after similes, and familiar expressions were the most explained. Finally, comparing the properties expressed in these explanations to normed property lists, we found that simile explanations typically expressed a novel conception of the topic–vehicle relationship. Therefore, we found that Internet posters use metaphors to convey an apt relationship, as found in previous laboratory studies, but prefer using a simile frame when they want to express a relationship that readers will find novel. (shrink)

Health equity is a global concern. Although health equity extends far beyond the equitable distribution of healthcare, equitable access to healthcare is essential to the achievement of health equity. In Canada, Indigenous Peoples experience inequities in health and healthcare access. Cultural safety and trauma‐ and violence‐informed care have been proposed as models of care to improve healthcare access, yet practitioners lack guidance on how to implement these models. In this paper, we build upon an existing framework of equity‐oriented care for (...) primary healthcare settings by proposing strategies to guide nurses in operationalizing cultural safety and trauma‐ and violence‐informed care into nursing practice at the individual level. This component is one strategy to redress inequitable access to care among Indigenous Peoples in Canada. We conceptualize barriers to accessing healthcare as intrapersonal, interpersonal, and structural. We then define three domains for nursing action: practicing reflexivity, prioritizing relationships, and considering the context. We have applied this expanded framework within the context of Indigenous Peoples in Canada as a way of illustrating specific concepts and focusing our argument; however, this framework is relevant to other groups experiencing marginalizing conditions and inequitable access to healthcare, and thus is applicable to many areas of nursing practice. (shrink)

Inequities in access to oncology care among Indigenous peoples in Canada are well documented. Access to oncology care is mediated by a range of factors; however, emerging evidence suggests that healthcare providers, including nurses, play a significant role in shaping healthcare access. The purpose of this study was to critically examine access to oncology care among Indigenous peoples in Canada from the perspective of oncology nurses. Guided by postcolonial theoretical perspectives, interpretive descriptive and critical discourse analysis methodologies informed study design (...) and data analysis. Oncology nurses were recruited from across Canada to complete an online survey (n = 78). Nurses identified a range of barriers experienced by Indigenous peoples when accessing oncology care, yet located these barriers primarily at the individual and systems levels. Nurses perceived themselves as mediators of access to oncology care; however, their efforts to facilitate access to care were constrained by the dominance of biomedicine within healthcare. Nurses' constructions of access to oncology care highlight the embedded narrative of individualism within nursing practice and the relative invisibility of racism as a determinant of equitable access to care among Indigenous peoples. This suggests a need for oncology nurses to better understand and incorporate structural determinants of health perspectives. (shrink)

BackgroundPreprint usage is growing rapidly in the life sciences; however, questions remain on the relative quality of preprints when compared to published articles. An objective dimension of quality that is readily measurable is completeness of reporting, as transparency can improve the reader’s ability to independently interpret data and reproduce findings.MethodsIn this observational study, we initially compared independent samples of articles published in bioRxiv and in PubMed-indexed journals in 2016 using a quality of reporting questionnaire. After that, we performed paired comparisons (...) between preprints from bioRxiv to their own peer-reviewed versions in journals.ResultsPeer-reviewed articles had, on average, higher quality of reporting than preprints, although the difference was small, with absolute differences of 5.0% [95% CI 1.4, 8.6] and 4.7% [95% CI 2.4, 7.0] of reported items in the independent samples and paired sample comparison, respectively. There were larger differences favoring peer-reviewed articles in subjective ratings of how clearly titles and abstracts presented the main findings and how easy it was to locate relevant reporting information. Changes in reporting from preprints to peer-reviewed versions did not correlate with the impact factor of the publication venue or with the time lag from bioRxiv to journal publication.ConclusionsOur results suggest that, on average, publication in a peer-reviewed journal is associated with improvement in quality of reporting. They also show that quality of reporting in preprints in the life sciences is within a similar range as that of peer-reviewed articles, albeit slightly lower on average, supporting the idea that preprints should be considered valid scientific contributions. (shrink)

The issue of advocacy has dominated discussion of the ethical dilemmas facing nurses. However, despite this, nurses seem to be no further towards a solution of how they can be effective advocates for patients without compromising their working identity or facing conflicts of loyalty. This article considers some of the problems around advocacy and, by the use of critical incidents written by nurses involved in a diploma module, attempts to highlight where the problem could lie. A communications model is outlined, (...) using a theoretical framework taken from the work of Jürgen Habermas, and applied to nursing practice. Finally, two examples are given from the research, which illustrate how the model could be used, highlighting the problems and pitfalls that still have to be overcome. The conclusion is a positive one, in that it suggests that advocacy is possible if nurses re-examine their practice in the light of the model proposed.Copyright of Nursing Ethics is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (shrink)

Graphical AbstractGene editing with engineered nucleases introduce double-strand breaks that are repaired by error-prone nonhomologous end-joining (NHEJ). In article number 1900126, Sara G. Trimidal et al. propose that the length and type or resulting indels can now be controlled by editing with different engineered nucleases or by manipulating the expression of NHEJ genes.

Genome editing with engineered nucleases (GEENs) introduce site‐specific DNA double‐strand breaks (DSBs) and repairs DSBs via nonhomologous end‐joining (NHEJ) pathways that eventually create indels (insertions/deletions) in a genome. Whether the features of indels resulting from gene editing could be customized is asked. A review of the literature reveals how gene editing technologies via NHEJ pathways impact gene editing. The survey consolidates a body of literature that suggests that the type (insertion, deletion, and complex) and the approximate length of indel edits (...) can be somewhat customized with different GEENs and by manipulating the expression of key NHEJ genes. Structural data suggest that binding of GEENs to DNA may interfere with binding of key components of DNA repair complexes, favoring either classical‐ or alternative‐NHEJ. The hypotheses have some limitations, but if validated, will enable scientists to better control indel makeup, holding promise for basic science and clinical applications of gene editing. Also see the video abstract here https://youtu.be/vTkJtUsLi3w. (shrink)

Terms such as ‘cultural competence’ and ‘transcultural nursing’ have comfortably taken their place in the lexicon of health care. Their high profile is a reflection of the diversity of western societies and health care’s commitment to provide care that is responsive to the values and beliefs of all who require treatment. However, the relationship between cultural competence and familiar ethical concepts such as patient autonomy has been an uneasy one. This article explores the moral foundations of cultural competence, ultimately locating (...) them in patient autonomy and patient good. The discussion of patient good raises questions about the moral relevance of a value’s rootedness in a particular culture. I argue that the moral justification for honoring cultural values has more to do with the fact that patients are strongly committed to them than it does with their cultural rootedness. Finally, I suggest an organizational approach to cultural competence that emphasizes overall organizational preparedness. (shrink)

Kant’s remark that the first Kritik should be read as a treatise on method rather than a system of doctrine lends support to recent forays against his theory of proof, for the comment promotes the mistaken supposition that his method can be studied independently of his commitments in ontology and other areas. Irony infects the criticisms in question because they set transcendental logic against a standard that Kant repudiates. The point will be illustrated by showing how Kant anticipates and blunts (...) a strong attack against his position on method. (shrink)

Do we directly perceive physical objects? What is the significance of the qualification ‘directly’ here? Austin famously denied that there was a unique interpretation by which we could make sense of the traditional debate in the philosophy of perception. I look here at Thompson Clarke’s discussion of G. E. Moore and surface perception to answer Austin’s scepticism.

Oocytes, eggs and blastomeres of the embryo are special cells that undergo rapid changes in structure and function at developmental transitions. These changes are frequently regulated by cytoplasmic signaling events, particularly at the developmental transition of fertilization, because the genome is largely inactivated at this time. Protein kinase C (PKC) is a signaling agent that acts after the sperm‐induced rise in calcium and has a central role in the remodeling of the structure of the egg into the zygote in many (...) species. PKC also acts during other developmental transitions. This kinase serves as a chronometer, which can choreograph the cell's remodeling events in both space and time. Several technical advancements discussed in this review have permitted a better understanding of the actions of PKC. (shrink)

Behrendt & Young's (B&Y's) theory offers a potentially important perspective on the neurobiology of schizophrenia, but it remains incomplete. In addition to bottom-up contributions, such as those associated with disturbances in sensory constraints on cognitive processes, a comprehensive model requires the integration of the consequences of abnormal top-down modulation of input processing for the evolution of “underconstrained” perceptions. Dysfunctional cholinergic modulation of input functions represents a necessary mechanism for the generation of false perceptions.

Nanomedicine is yielding new and improved treatments and diagnostics for a range of diseases and disorders. Nanomedicine applications incorporate materials and components with nanoscale dimensions where novel physiochemical properties emerge as a result of size-dependent phenomena and high surface-to-mass ratio. Nanotherapeutics and in vivo nanodiagnostics are a subset of nanomedicine products that enter the human body. These include drugs, biological products, implantable medical devices, and combination products that are designed to function in the body in ways unachievable at larger scales. (...) Nanotherapeutics andin vivonanodiagnostics incorporate materials that are engineered at the nanoscale to express novel properties that are medicinally useful. These nanomedicine applications can also contain nanomaterials that are biologically active, producing interactions that depend on biological triggers. Examples include nanoscale formulations of insoluble drugs to improve bioavailability and pharmacokinetics, drugs encapsulated in hollow nanoparticles with the ability to target and cross cellular and tissue membranes and to release their payload at a specific time or location, imaging agents that demonstrate novel optical properties to aid in locating micrometastases, and antimicrobial and drug-eluting components or coatings of implantable medical devices such as stents. (shrink)

Why do we watch and like horror films? Despite a century of horror film-making and en-tertainment, little research has examined the human motivation to watch fictional horror and how horror film influences individuals’ behavioural, cognitive and emotional re-sponses. This review provides the first synthesis of the empirical literature on the psy-chology of horror film using multi-disciplinary research from psychology, psychotherapy, communication studies, development studies, clinical psychology, and media studies. The paper considers the motivations for people’s decision to watch horror, why (...) people enjoy horror, how individual differences influence responses to, and preference for, hor-ror film, how exposure to horror film changes behaviour, how horror film is designed to achieve its effects, why we fear and why we fear specific classes of stimuli, and how lik-ing for horror develops during childhood and adolescence. The literature suggests that (1) low empathy and fearfulness are associated with more enjoyment and desire to watch horror film but that specific dimensions of empathy are better predictors of people’s re-sponses than are others; (2) there is a positive relationship between sensation-seeking and horror enjoyment/preference but this relationship is not consistent; (3) men and boys prefer to watch, enjoy and seek our horror more than do women and girls; (4) women are more prone to disgust sensitivity or anxiety than are men and this may mediate the sex difference in the enjoyment of horror; (5) younger children are afraid of symbolic stimuli whereas older children become afraid of concrete or realistic stimuli; (6) in terms of coping with horror, physical coping strategies are more successful in younger children; priming with information about the feared object reduces fear and increases children’s enjoyment of frightening television and film. A number of limitations in the literature are identified, including the multifarious range of horror stimuli used in studies, disparities in methods, small sample sizes, and a lack of research on cross-cultural differences and similarities. Ideas for future research are explored. (shrink)

This paper is a critical review of Mitchell Green’s Self-Expression . The principal focus is on Green’s contention that all expression is at route, a form of signalling by an agent or by some mechanism of the organism which has been evolutionary selected for signalling. Starting from the idea that in some but not all expression an agent seeks to express his or her self, I question the centrality of communication to the idea of expression.

In this paper I discuss Hume’s theory of pride and the ‘remarkable mechanism’ of sympathy. In the first part of the paper I outline the ways in which Hume’s theory can accommodate the sense in which the passions are directed on things or possess intentionality while still holding to his view that passions are simple feelings. In the second part of the paper I consider a problem internal to Hume’s account of pride which arises in his discussion of the love (...) of fame and the functioning of sympathy; I explain how the tensions can be reconciled by recognising that Hume’s theory of sympathy is more nuanced than has commonly been recognized. In the third part I turn back to the evaluation of Hume’s theory of pride and argue that while it is unfair to complain that Hume does not make self-evaluation a central component of pride, Hume’s treatment of the idea of self in his theory of the passions is inadequate because he can make no proper room for the phenomenon of vicarious pride. (shrink)

BackgroundBiobanking biospecimens and consent are common practice in paediatric research. We need to explore children and young people’s (CYP) knowledge and perspectives around the use of and consent to biobanking. This will ensure meaningful informed consent can be obtained and improve current consent procedures.MethodsWe designed a survey, in co-production with CYP, collecting demographic data, views on biobanking, and consent using three scenarios: 1) prospective consent, 2) deferred consent, and 3) reconsent and assent at age of capacity. The survey was disseminated (...) via the Young Person’s Advisory Group North England (YPAGne) and participating CYP’s secondary schools. Data were analysed using a qualitative thematic approach by three independent reviewers (including CYP) to identify common themes. Data triangulation occurred independently by a fourth reviewer.ResultsOne hundred two CYP completed the survey. Most were between 16–18 years (63.7%, N = 65) and female (66.7%, N = 68). 72.3% had no prior knowledge of biobanking (N = 73).Acceptability of prospective consent for biobanking was high (91.2%, N = 93) with common themes: ‘altruism’, ‘potential benefits outweigh individual risk’, 'frugality', and ‘(in)convenience’.Deferred consent was also deemed acceptable in the large majority (84.3%, N = 86), with common themes: ‘altruism’, ‘body integrity’ and ‘sample frugality’. 76.5% preferred to reconsent when cognitively mature enough to give assent (N = 78), even if parental consent was previously in place. 79.2% wanted to be informed if their biobanked biospecimen is reused (N = 80).ConclusionProspective and deferred consent acceptability for biobanking is high among CYP in the UK. Altruism, frugality, body integrity, and privacy are the most important themes. Clear communication and justification are paramount to obtain consent. Any CYP with capacity should be part of the consenting procedure, if possible. (shrink)

The problems of perception feature centrally in work within what we now think of as different traditions of philosophy in the early part of the twentieth century, most notably in the sense-datum theories of early analytic philosophy together with the vigorous responses to them over the next forty years, but equally in the discussions of pre-reflective consciousness of the world characteristic of German and French phenomenologists. In the English-speaking world one might mark the beginning of the period with Russell’s The (...) Problems of Philosophy (Russell 1912) and its nemesis in Austin’s Sense and Sensibilia (Austin 1962 – published posthumously, but given originally as lectures at the end of our period in 1947). On the continent, a corresponding route takes us from Husserl’s Logical Investigations (Husserl 1900/1) to Merleau-Ponty’s Phenomenology of Perception.. (shrink)