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Previous genetic association studies have failed to identify loci robustly associated with sepsis, and there have been no published genetic association studies or polygenic risk score analyses of patients with septic shock, despite evidence suggesting genetic factors may be involved. We systematically collected genotype and clinical outcome data in the context of a randomized controlled trial from patients with septic shock to enrich the presence of disease-associated genetic variants. We performed genomewide association studies of susceptibility and mortality in septic shock using 493 patients with septic shock and 2442 population controls, and polygenic risk score analysis to assess genetic overlap between septic shock risk/mortality with clinically relevant traits. One variant, rs9489328, located in AL589740.1 noncoding RNA, was significantly associated with septic shock (p = 1.05 × 10–10); however, it is likely a false-positive. We were unable to replicate variants previously reported to be associated (p < 1.00 × 10–6 in previous scans) with susceptibility to and mortality from sepsis. Polygenic risk scores for hematocrit and granulocyte count were negatively associated with 28-day mortality (p = 3.04 × 10–3; p = 2.29 × 10–3), and scores for C-reactive protein levels were positively associated with susceptibility to septic shock (p = 1.44 × 10–3). Results suggest that common variants of large effect do not influence septic shock susceptibility, mortality and resolution; however, genetic predispositions to clinically relevant traits are significantly associated with increased susceptibility and mortality in septic individuals.
Executive functions (EF) drive health and educational outcomes and therefore are increasingly common treatment targets. Most treatment trials rely on questionnaires to capture meaningful change because ecologically valid, pediatric performance-based EF tasks are lacking. The Executive Function Challenge Task (EFCT) is a standardized, treatment-sensitive, objective measure which assesses flexibility and planning in the context of provocative social interactions, making it a “hot” EF task.
We investigate the structure, reliability, and validity of the EFCT in youth with autism (Autism Spectrum Disorder; n = 129), or attention deficit hyperactivity disorder with flexibility problems (n = 93), and typically developing (TD; n = 52) youth.
The EFCT can be coded reliably, has a two-factor structure (flexibility and planning), and adequate internal consistency and consistency across forms. Unlike a traditional performance-based EF task (verbal fluency), it shows significant correlations with parent-reported EF, indicating ecological validity. EFCT performance distinguishes youth with known EF problems from TD youth and is not significantly related to visual pattern recognition, or social communication/understanding in autistic children.
The EFCT demonstrates adequate reliability and validity and may provide developmentally appropriate, treatment-sensitive, and ecologically valid assessment of “hot” EF in youth. It can be administered in controlled settings by masked administrators.
Heterotrophic soil protists encompass lineages that are both evolutionarily ancient and highly diverse, providing an untapped wealth of scientific insight. Yet the diversity of free-living heterotrophic terrestrial protists is still largely unknown. To contribute to our understanding of this diversity, we present a checklist of heterotrophic protists currently reported from terrestrial Antarctica, for which no comprehensive evaluation currently exists. As a polar continent, Antarctica is especially susceptible to rising temperatures caused by anthropogenic climate change. Establishing a baseline for future conservation efforts of Antarctic protists is therefore important. We performed a literature search and found 236 taxa identified to species and an additional 303 taxa identified to higher taxonomic levels in 54 studies spanning over 100 years of research. Isolated by distance, climate and the circumpolar vortex, Antarctica is the most extreme continent on Earth: it is not unreasonable to think that it may host physiologically and evolutionarily unique species of protists, yet currently most species discovered in Antarctica are considered cosmopolitan. Additional sampling of the more extreme intra-continental zones will probably result in the discovery of more novel and unique taxa.
There is increasing evidence for shared genetic susceptibility between schizophrenia and bipolar disorder. Although genetic variants only convey subtle increases in risk individually, their combination into a polygenic risk score constitutes a strong disease predictor.
To investigate whether schizophrenia and bipolar disorder polygenic risk scores can distinguish people with broadly defined psychosis and their unaffected relatives from controls.
Using the latest Psychiatric Genomics Consortium data, we calculated schizophrenia and bipolar disorder polygenic risk scores for 1168 people with psychosis, 552 unaffected relatives and 1472 controls.
Patients with broadly defined psychosis had dramatic increases in schizophrenia and bipolar polygenic risk scores, as did their relatives, albeit to a lesser degree. However, the accuracy of predictive models was modest.
Although polygenic risk scores are not ready for clinical use, it is hoped that as they are refined they could help towards risk reduction advice and early interventions for psychosis.
Declaration of interest
R.M.M. has received honoraria for lectures from Janssen, Lundbeck, Lilly, Otsuka and Sunovian.
The end of the last Ice Age in Britain (c. 11500 BP) created major disruption to the biosphere. Open habitats were succeeded by more wooded landscapes, and changes occurred to the fauna following the abrupt disappearance of typical glacial herd species, such as reindeer and horse (Conneller & Higham 2015). Understanding the impact of these changes on humans and how quickly they were able to adapt may soon become clearer, due to recent discoveries in the Colne Valley on the western edge of Greater London, north of the River Thames. An exceptionally well-preserved open-air site was discovered in 2014 as part of a wider project of archaeological investigation and excavation carried out by Wessex Archaeology (2015), on behalf of CEMEX UK. The site, at Kingsmead Quarry in Horton, is unusual because it has good organic preservation and, in addition to worked flint artefacts, it has yielded groups of articulated horse bone. The extreme rarity of such sites of this period in Britain makes this discovery especially significant and re-emphasises the potential importance of the Colne Valley (Lacaille 1963; Lewis 2011; Morgi et al. 2011).
In Ramsey theory one wishes to know how large a collection of objects can be while avoiding a particular substructure. A problem of recent interest has been to study how large subsets of the natural numbers can be while avoiding three-term geometric progressions. Building on recent progress on this problem, we consider the analogous problem over quadratic number fields. We first construct high-density subsets of the algebraic integers of an imaginary quadratic number field that avoid three-term geometric progressions. When unique factorization fails, or over a real quadratic number field, we instead look at subsets of ideals of the ring of integers. Our approach here is to construct sets ‘greedily’, a generalization of the greedy set of rational integers considered by Rankin. We then describe the densities of these sets in terms of values of the Dedekind zeta function. Next, we consider geometric-progression-free sets with large upper density. We generalize an argument by Riddell to obtain upper bounds for the upper density of geometric-progression-free subsets, and construct sets avoiding geometric progressions with high upper density to obtain lower bounds for the supremum of the upper density of all such subsets. Both arguments depend critically on the elements with small norm in the ring of integers.
The borderline between the periods commonly termed "medieval" and "Renaissance", or "medieval" and "early modern", is one of the most hotly, energetically and productively contested faultlines in literary history studies. The essays presented in this volume both build upon and respond to the work of Professor Helen Cooper, a scholar who has long been committed to exploring the complex connectionsand interactions between medieval and Renaissance literature. The contributors re-examine a range of ideas, authors and genres addressed in her work, including pastoral, chivalric romance, early English drama, and the writings of Chaucer, Langland, Spenser and Shakespeare. As a whole, the volume aims to stimulate active debates on the ways in which Renaissance writers used, adapted, and remembered aspects of the medieval.
Andrew King is Lecturer in Medieval and Renaissance Literature at University College, Cork; Matthew Woodcock is Senior Lecturer in Medieval and Renaissance Literature at the University of East Anglia.
Contributors: Joyce Boro, Aisling Byrne, Nandini Das, Mary C. Flannery, Alexandra Gillespie, Andrew King, Megan G. Leitch, R.W. Maslen, Jason Powell,Helen Vincent, James Wade, Matthew Woodcock
A patient who was a devout Christian was admitted to hospital as an emergency. She tried to explain to the duty psychiatrist the importance of her belief in ‘the Holy Ghost’, only to hear it reported in the ward round the next day that she had been seeing ghosts.
In this chapter, I aim to show that the narrative set in motion when a patient is seen by a psychiatrist is not only an account of an individual's life experience but also attuned to the expectations of the psychiatrist – more than either of them may be aware. This is especially relevant to soul narrative, which is often invested with profound personal meaning, yet can lead to confusion when not understood, or else is likely to remain unvoiced if a patient senses that their spiritual beliefs and concerns are not given credence. I conclude by illustrating how the soul narrative, when encouraged, can bring real therapeutic benefits.
The pre-eminence of medical diagnosis
In general medicine, taking a patient's history is followed by hands-on examination of the body, feeling for lumps and bumps, listening to the heart and lungs and testing for abnormalities of the nervous system, followed when needed by a battery of investigations. The unspoken contract between physician and patient enables doctors to divide their attention between relating to their patients as persons and yet examining their bodies with the detachment needed to identify pathology and arrive at an accurate diagnosis (in Greek, dia means ‘stand apart’, gnosis means ‘discern’).
The art of diagnosis has its roots in the ancient civilisations of Egypt, Greece and China. But the physician of our time is heir principally to a scientific method that began during the Renaissance with the study of human anatomy and which has brought extraordinary knowledge of how the body works. A correct diagnosis will generally indicate a disease that has recognisable pathology, a cause (aetiology), a natural history (it may progress or remit) and an outcome (prognosis).
I read this book with fascination and interest, and it confirmed my feeling that storytelling is central to psychiatric practice, alongside a deep respect for the patient's own spiritual journey. Two contemporary themes have been employed by the editors to enable psychiatrists better to understand – and therefore be more effective in the treatment of – their patients. First, the spiritual and religious concerns of patients, after years of neglect by psychiatry, have now been accepted as an integral part of psychiatric assessment and care. Second, there has been much recent interest from many quarters, including psychiatry, in the nature and application of narrative – what it is, how it affects the relationship with, and between, our patients, and how it makes for better treatment. These dual themes are maintained throughout this book, which is written for mental health professionals, hospital chaplains and others interested in the relationship of mental health to spirituality. The practical rather than theoretical is underscored, emphasising how users, carers and relatives can all enlist spirituality and narrative for their well-being.
The fourteen chapters range widely over different areas of psychiatric practice and theoretical viewpoint. Most are written by psychiatrists whose primary role has been the care of patients. Transcultural psychiatry is shown to be intimately involved with both narrative and the person's spiritual and religious convictions. Descriptive psychopathology depends entirely on the patient's story, which often includes their spiritual and religious understanding. Psychotherapy is greatly enriched by taking into account the spiritual aspects of life; story is pre-eminent, with narrative an essential aspect of therapy. Other chapters discuss the core psychiatric problems of depression, anxiety, psychosis, psychiatry of old age and mentally ill offenders, in all of which the interweaving themes of narrative and spirituality are prominent. There are moving stories from both a service user and from people seeking help from a mental health chaplain that show the significance of their beliefs in aiding the recovery process.