An investigation of elite athletes' and coaches' perceptions of mental ill-health in elite athletes

Research suggests elite athletes have an equal, possibly higher, probability of developing mental ill-health as the general population. However understanding of these issues amongst athletes and coaches remains largely unknown. The perceptions of 20 elite athletes and 16 elite coaches of mental ill-health amongst elite athletes were explored. Two concurrent, three round Delphi methods, using descriptive statistics and thematic analysis, were used to compare groups’ responses. Athletes and coaches expressed different opinions and experiences of mental ill-health amongst elite athletes. However, both felt the pressure athletes place upon themselves is a significant contributing factor and that obsessive compulsive disorder (OCD) and anxiety may be particularly prevalent. Whilst associated stigma was thought to be a barrier to support seeking, both groups felt sport and clinical psychologists would provide the most appropriate support, with coaches playing an important role. Implications for coaches, clinical and sport psychologists are explored and suggestions for future research are presented

Quantitative principles of cis-translational control by general mRNA sequence features in eukaryotes.

BackgroundGeneral translational cis-elements are present in the mRNAs of all genes and affect the recruitment, assembly, and progress of preinitiation complexes and the ribosome under many physiological states. These elements include mRNA folding, upstream open reading frames, specific nucleotides flanking the initiating AUG codon, protein coding sequence length, and codon usage. The quantitative contributions of these sequence features and how and why they coordinate to control translation rates are not well understood.ResultsHere, we show that these sequence features specify 42-81% of the variance in translation rates in Saccharomyces cerevisiae, Schizosaccharomyces pombe, Arabidopsis thaliana, Mus musculus, and Homo sapiens. We establish that control by RNA secondary structure is chiefly mediated by highly folded 25-60 nucleotide segments within mRNA 5' regions, that changes in tri-nucleotide frequencies between highly and poorly translated 5' regions are correlated between all species, and that control by distinct biochemical processes is extensively correlated as is regulation by a single process acting in different parts of the same mRNA.ConclusionsOur work shows that general features control a much larger fraction of the variance in translation rates than previously realized. We provide a more detailed and accurate understanding of the aspects of RNA structure that directs translation in diverse eukaryotes. In addition, we note that the strongly correlated regulation between and within cis-control features will cause more even densities of translational complexes along each mRNA and therefore more efficient use of the translation machinery by the cell

Epidemiology of blood component transfusion in Eastern Scotland

BACKGROUND & AIMS Blood transfusion is a globally accepted medical intervention that can save life and improve health but like many valuable therapies it also poses risk. From the patient perspective, therefore, it should therefore be prescribed only when it is absolutely appropriate to do so. Pressures on the blood supply also make it essential to promote the appropriate and effective use of allogeneic blood so as to preserve supply. The way blood is used within a given population needs to be carefully monitored and published evidence on blood use is available for various populations and settings. However, there is an increasing need for evidence about the patterns of use by clinical case group that can be used to identify areas where change in transfusion and clinical practice may be needed. The Scottish Transfusion Epidemiology Project (STEP) aimed to assess the feasibility of linking routine datasets of transfusion data and clinical data for blood use analysis. This thesis reports on the study of STEP data in order to describe blood component use by clinical case group and its application in exploring transfusion practice.Methods This study employed computer-based methods to link the STEP data of transfusion day records (Scottish National Blood Transfusion Service) and Scottish Morbidity Record SMROl/cancer/death records (ISD Scotland). Clinically informed methods were devised to attribute blood component use to purposely defined clinical case groups. The study dataset was analysed to describe blood component use by age, gender and intensity of transfusion, and for surgical procedure and haematological disease clinical case groups. The impact of changes in transfusion practice and changes in population demographics on future blood use were modelled and further, additional applications were explored.RESULTS The study dataset comprises information on blood component use for a subset of Scottish hospitals that received approximately 38% of the red blood cell units delivered by the Scottish National Blood Transfusion Service in the year 2000. The dataset contains 41,431 transfusion day records of blood component use that represent 21,309 transfused patients and the use of 60,130 red blood cell units, 4,795 platelet units, 9,446 fresh frozen plasma units, and 1,759 cryoprecipitate units. For red blood cell, platelet and plasma use, although a small proportion of patients were transfused intensively, they nevertheless accounted for a large proportion of blood component units17,403 (29%) red blood cell units were attributed to surgical events defined by red cell using procedures; 7,286 (12%) red blood cell units were attributed to 726 patients with a diagnosis of pre-malignant or malignant haematological disease. The remaining 59% of red blood cell units were not classified by clinical case groups in this study and represent areas for future work.Between 2000 and 2031 the Scottish population is projected to remain fairly stable in size but to be proportionately older. Modelling the impact of this on the demand for blood indicates that by 2031 there will be a requirement for 38% more red blood cell units. The impact of applying best practice figures and potential savings using intra-operative cell salvage were modelled and identified potential savings in blood use.CONCLUSION The study linked available routine data and employed specific, novel methods to enable analysis of blood component transfusion, and specifically, blood component use by clinical case groups. The potential for employing the data in modelling analyses of blood component use and related applications was also demonstrated. Recommendations for future approaches to studying the clinical use of blood are made. The findings of the study can be used for future planning purposes and to inform guidelines and policy, with the aim of changing practice and promoting the appropriate use of blood

Audience Immersion: environment, interactivity, narrative in the work of Punchdrunk

The phrase immersive theatre has experienced a surge in popularity in recent years, and is often applied loosely. In 2012 (‘theatre roundup: advice for playwrights’) Lyn Gardner noted that ‘immersive is theatre’s new buzzword’ and expressed irritation with its often vague and unspecific application, commenting on ‘marketeers who seem to be applying the term “immersive” to practically anything that isn’t a play by David Hare.’ A specialised vocabulary and set of critical approaches are required. This thesis is about audience immersion in the work of Punchdrunk, a pioneering company working in the form. The thesis proposes that immersive theatre (the theatrical form) and immersive experience (the sensation) have a reciprocal relationship. The thesis begins with an overview of approaches to audience in theatre scholarship and other fields, and establishes a definition of immersive experience that will be applied to case studies in the chapters. The thesis is divided into three sections that consider topics integral to Punchdrunk’s theatre: interactive elements; a fractured and nonlinear approach to narrative; and the creation of scenographically rich environments. The chapters consider the relationship between these topics and immersive experience. The thesis is interested in how immersive experience is created and maintained, and discussed and framed in wider discourse. The first section is about interactivity and immersion. Chapter 1 considers various approaches to interactivity and proposes a multivalent model. Chapter 2 applies this model to a discussion of interactivity and immersive experience in The Drowned Man. Chapter 3 widens the definition of interactivity to consider audience engagement beyond the moment of the theatrical encounter. The second section is about narrative and immersion. Chapter 4 outlines current critical approaches to narrative, and discusses immersion in the interplay of story structure and theatrical structure, using the linear The Crash of the Elysium as a case study. Following on from this, Chapter 5 considers how immersive experience is created and maintained in the context of a Punchdrunk trademark: a nonlinear structure, with scenes in non-chronological order encountered only when a wandering spectator comes across them. Chapter 6 draws on the narrative ‘vs’ ludology debate in the field of gaming; a debate concerned with what a player is actually immersed in – the story or the mechanics of play. The chapter considers immersive experience and story in the Sleep No More project Punchdrunk undertook with MIT Media Lab in 2012, which used gaming mechanics to explore ‘remote and real world interconnected theatrical immersion’. The final section is about environment and immersion. Chapter 7 outlines approaches to environment and draws on methodological approaches from site-specific performance to discuss how immersive experience manifests in the interplay between the original site and the creation of a fictional world in/on that site.AHR

Actions of Agonists, Fipronil and Ivermectin on the Predominant In Vivo Splice and Edit Variant (RDLbd, I/V) of the Drosophila GABA Receptor Expressed in Xenopus laevis Oocytes

Ionotropic GABA receptors are the targets for several classes of insecticides. One of the most widely-studied insect GABA receptors is RDL (resistance to dieldrin), originally isolated from Drosophila melanogaster. RDL undergoes alternative splicing and RNA editing, which influence the potency of GABA. Most work has focussed on minority isoforms. Here, we report the first characterisation of the predominant native splice variant and RNA edit, combining functional characterisation with molecular modelling of the agonist-binding region. The relative order of agonist potency is GABA> muscimol> TACA> β-alanine. The I/V edit does not alter the potency of GABA compared to RDLbd. Docking calculations suggest that these agonists bind and activate RDLbdI/V through a similar binding mode. TACA and β-alanine are predicted to bind with lower affinity than GABA, potentially explaining their lower potency, whereas the lower potency of muscimol and isoguvacine cannot be explained structurally from the docking calculations. The A301S (resistance to dieldrin) mutation reduced the potency of antagonists picrotoxin, fipronil and pyrafluprole but the I/V edit had no measurable effect. Ivermectin suppressed responses to GABA of RDLbdI/V, RDLbd and RDLbdI/VA301S. The dieldrin resistant variant also showed reduced sensitivity to Ivermectin. This study of a highly abundant insect GABA receptor isoform will help the design of new insecticides

An investigation of athletes’ and coaches’ perceptions of mental ill-health in elite athletes

Research suggests elite athletes have an equal, or in some circumstances possibly higher, probability of developing mental ill health as the general population, however understanding of these issues amongst athletes and coaches remains largely unknown. The perceptions of mental health problems amongst 19 elite athletes and 16 coaches were explored using two concurrent, three round Delphi surveys and the responses compared. Athletes and coaches expressed different opinions and experiences of mental ill health amongst elite athletes. However, both felt the pressure athletes place upon themselves is a significant contributing factor and that obsessional compulsive tendencies and anxiety may be particularly prevalent. Whilst associated stigma was thought to be a barrier to support seeking, both groups felt sport and clinical psychologists would provide the most appropriate support, with coaches playing an important signposting role. Implications for athletes, coaches, clinical and sport psychologists are explored and suggestions for future research are presented

Robust estimators reveal changing geomagnetic field behaviour through the Cenozoic

The Fisher distribution is central to palaeomagnetism but presents several problems when used to characterize geomagnetic field directions as observed in sequences of volcanic rocks. First, it introduces a shallowing effect when used to define the mean of any group of directional unit vectors. This is problematic because it can suggest the presence of persistent non-axial dipole components when none are present. More importantly, it fails to capture the observed ‘long tail’ in distributions of both directions and associated virtual geomagnetic poles in terms of angular distance from a central direction. To achieve a good fit to data, it therefore requires the introduction of a second distribution (and therefore the estimation of additional parameters) or the arbitrary removal of data. Here we present a new distribution to describe palaeomagnetic directions and demonstrate that it overcomes both of these problems, generating robust indicators of both the central direction (or pole position) and the spread of palaeomagnetic data as defined by unit vectors. Starting from the assumption that poles (or directions) have an expected colatitude, rather than a mean location, we derive the spherical exponential distribution. We demonstrate that this new distribution provides a good fit to palaeomagnetic data sets from seven large igneous provinces between 15 and 65 Ma and also those produced by numerical dynamo models. We also use it to derive a new shape parameter which may be used as a diagnostic tool for testing goodness of fit of models to data and use this to argue for a shift in geomagnetic behaviour between 5 and 15 Ma. Furthermore, we point out that this new statistic can be used to determine the most appropriate distribution to be used when constructing confidence limits for poles

On the atomic structure of cocaine in solution

Cocaine is an amphiphilic drug which has the ability to cross the blood–brain barrier (BBB). Here, a combination of neutron diffraction and computation has been used to investigate the atomic scale structure of cocaine in aqueous solutions. Both the observed conformation and hydration of cocaine appear to contribute to its ability to cross hydrophobic layers afforded by the BBB, as the average conformation yields a structure which might allow cocaine to shield its hydrophilic regions from a lipophilic environment. Specifically, the carbonyl oxygens and amine group on cocaine, on average, form ~5 bonds with the water molecules in the surrounding solvent, and the top 30% of water molecules within 4 Å of cocaine are localized in the cavity formed by an internal hydrogen bond within the cocaine molecule. This water mediated internal hydrogen bonding suggests a mechanism of interaction between cocaine and the BBB that negates the need for deprotonation prior to interaction with the lipophilic portions of this barrier. This finding also has important implications for understanding how neurologically active molecules are able to interact with both the blood stream and BBB and emphasizes the use of structural measurements in solution in order to understand important biological function.Peer ReviewedPostprint (author's final draft

Three-dimensional morphology and gene expression in the Drosophila blastoderm at cellular resolution II: dynamics.

BackgroundTo accurately describe gene expression and computationally model animal transcriptional networks, it is essential to determine the changing locations of cells in developing embryos.ResultsUsing automated image analysis methods, we provide the first quantitative description of temporal changes in morphology and gene expression at cellular resolution in whole embryos, using the Drosophila blastoderm as a model. Analyses based on both fixed and live embryos reveal complex, previously undetected three-dimensional changes in nuclear density patterns caused by nuclear movements prior to gastrulation. Gene expression patterns move, in part, with these changes in morphology, but additional spatial shifts in expression patterns are also seen, supporting a previously proposed model of pattern dynamics based on the induction and inhibition of gene expression. We show that mutations that disrupt either the anterior/posterior (a/p) or the dorsal/ventral (d/v) transcriptional cascades alter morphology and gene expression along both the a/p and d/v axes in a way suggesting that these two patterning systems interact via both transcriptional and morphological mechanisms.ConclusionOur work establishes a new strategy for measuring temporal changes in the locations of cells and gene expression patterns that uses fixed cell material and computational modeling. It also provides a coordinate framework for the blastoderm embryo that will allow increasingly accurate spatio-temporal modeling of both the transcriptional control network and morphogenesis