'Why did the window break when it was hit by the stone? Because the window is brittle and the stone is hard; hardness and brittleness are powers, dispositional properties or dispositions.' Dispositions are essential to our understanding of the world. This book is a record of the debate on the nature of dispositions between three distinguished philosophers - D. M. Armstrong, C. B. Martin and U. T. Place - who have been thinking about dispositions all their working lives. Their (...) distinctive accounts cover many of the issues surrounding dispositions such as the nature of mind, matter, universals, existence, laws of nature and causation. Dispositions illuminates this central topic in analytic philosophy and at the same time highlights deeper concerns of metaphysics. (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)

Dispositions are essential to our understanding of the world. Dispositions: A Debate is an extended dialogue between three distinguished philosophers - D.M. Armstrong, C.B. Martin and U.T. Place - on the many problems associated with dispositions, which reveals their own distinctive accounts of the nature of dispositions. These are then linked to other issues such as the nature of mind, matter, universals, existence, laws of nature and causation.

Raising a child with an autism spectrum disorder (ASD) is a stressful experience and has been associated with poor maternal mental health and increased maternal emotional distress. However, the experiences of fathers of children with ASD are largely unexplored and the coping strategies these men employ to cope with the challenges they face have received little research attention. This research aimed to explore the phenomenological experiences of fathers of preschool children with ASD by gaining a better understanding of the manner (...) in which these individuals attempted to cope with their situation. A multiple, single-case study design was employed and five participants were recruited via two local paediatric practices. Semi-structured interviews were conducted with the participants and data were analysed making use of Interpretative Phenomenological Analysis (IPA). This analysis yielded three superordinate themes, which were labelled as follows: (a) the experience of fathering a child with ASD, (b) challenges of fathering a child with ASD, and (c) coping with fathering a child with ASD. The results suggest that the fathers of children with ASD experience their parental role as stressful. The participants in the current study related the stress they experienced to a number of challenges associated directly with their children’s behaviour, as well as to the effects that parenting a child with ASD had on their own wellbeing and functioning. The participants reported making use of a number of coping strategies in order to deal with the challenges they faced. The participants used both problem-focussed and avoidant coping strategies. The results are discussed and recommendations made with regard to future research. (shrink)

The Jesus Sutras: Rediscovering the lost religion of Taoist Christianity. Martin Palmer. Piatkus, London 2001. xvi, 270 pp. £17.99. ISBN 0 7499 2250 8.

Current UK legislation is impacting upon the feasibility and cost-effectiveness of medical record-based research aimed at benefiting the NHS and the public heath. Whereas previous commentators have focused on the Data Protection Act 1998, the Health and Social Care Act 2001 is the key legislation for public health researchers wishing to access medical records without written consent. The Act requires researchers to apply to the Patient Information Advisory Group for permission to access medical records without written permission. We present a (...) case study of the work required to obtain the necessary permissions from PIAG in order to conduct a large scale public health research project. In our experience it took eight months to receive permission to access basic identifying information on individuals registered at general practices, and a decision on whether we could access clinical information in medical records without consent took 18 months. Such delays pose near insurmountable difficulties to grant funded research, and in our case £560 000 of public and charitable money was spent on research staff while a large part of their work was prohibited until the third year of a three year grant. We conclude by arguing that many of the current problems could be avoided by returning PIAG’s responsibilities to research ethics committees, and by allowing “opt-out” consent for many public health research projects. (shrink)

Here we describe how more important findings were obtained in a delirium study by using an informal assessment of mental capacity, and, in those who lacked capacity, obtaining consent later when or if capacity returned or a proxy was found. From a total of 233 patients 23 patients lacked capacity as judged by our informal capacity judgment and 210 did not. Of those who lacked capacity, 13 agreed to enter in the study. Six of them regained capacity later. When these (...) 13 participants were excluded from analysis, significant findings were no longer evident. These results show that by the inclusion of subjects who lacked capacity the results of analyses of the condition from whish they suffer are altered. We suggest that this approach to the study of delirium is more ethical than the usual system of strict exclusion of people who lack capacity to give consent and for whom assent is not available. (shrink)

This white paper outlines the plans of the History Philosophy Culture Working Group of the Next Generation Event Horizon Telescope Collaboration.

Psychiatric disorders present distinct clinical challenges which are partly attributable to their multifactorial aetiology and the absence of laboratory tests that can be used to confirm diagnosis or predict risk. Psychiatric disorders are highly heritable, but also polygenic, with genetic risk conferred by interactions between thousands of variants of small effect that can be summarized in a polygenic risk score. We discuss four areas in which the use of polygenic risk scores in psychiatric research and clinical contexts could have ethical (...) implications. First, there is concern that clinical use of polygenic risk scores may exacerbate existing health inequities. Second, research findings regarding polygenic risk could be misinterpreted in stigmatising or discriminatory ways. Third, there are concerns associated with testing minors as well as eugenics concerns elicited by prenatal polygenic risk testing. Fourth, potential challenges that could arise with the feedback and interpretation of high polygenic risk for a psychiatric disorder would require consideration. While there would be extensive overlap with the challenges of feeding back genetic findings in general, the potential clinical use of polygenic risk scoring warrants discussion in its own right, given the recency of this possibility. To this end, we discuss how lay interpretations of risk and genetic information could intersect. Consideration of these factors would be necessary for ensuring effective and constructive communication and interpretation of polygenic risk information which, in turn, could have implications for the uptake of any therapeutic recommendations. Recent advances in polygenic risk scoring have major implications for its clinical potential, however, care should be taken to ensure that communication of polygenic risk does not feed into problematic assumptions regarding mental disorders or support reductive interpretations. (shrink)

Compiled by an archaeologist and philosopher of science, Science at the Frontiers: Perspectives on the History and Philosophy of Science supplements current literature in the history and philosophy of science with essays approaching the traditional problems of the field from new perspectives and highlighting disciplines usually overlooked by the canon. William H. Krieger brings together scientists from a number of disciplines to answer these questions and more in a volume appropriate for both students and academics in the field.

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)

This paper first appeared in Modern Theology, Vol. 6, No. 3, July 1989. Copyright (c) Basil Blackwell Publisher Ltd., Oxford. Reprinted by permission.