Thinking Aloud: Stress and coping in junior cricket batsman during challenge and threat states

The present study examined stress and coping of cricket batsmen during challenge and threat states using the Think-Aloud method. Ten male elite-level junior cricket batsmen took part in the study. A repeated measures design was implemented, with participants verbalizing while both in (a) a threat state and (b) a challenge state. Participants were required to score 36 runs in 30 balls during the threat condition and 15 runs in 30 balls during the challenge condition. Verbalizations were subsequently transcribed verbatim and analyzed for stressors, coping strategies, and any other reoccurring themes. A paired-samples t-test was conducted to examine differences in the number of verbalizations made for each theme between conditions. Ten secondary themes were grouped into four primary themes; these included (a) stressors, (b) problem-focused coping, (c) emotion-focused coping, and (d) gathering information. There were significant differences( p≤0.05) between stressor verbalizations, with significantly more verbalizations made by participants during a threat state. No significant differences were found between any other themes. Thus, during a threat state, participants reported significantly more stressor verbalizations compared to a challenge state, while there were no significant differences in coping strategies reported (p>0.05). This finding offers a potential explanation for why athletic performance diminishes when in a threat state, as athletes then experience a greater number of stressors but do not report engaging in more coping strategies

Diabetic retinopathy: a complex pathophysiology requiring novel therapeutic strategies.

INTRODUCTION: Diabetic retinopathy (DR) is the leading cause of vision loss in the working age population of the developed world. DR encompasses a complex pathology, and one that is reflected in the variety of currently available treatments, which include laser photocoagulation, glucocorticoids, vitrectomy and agents which neutralize vascular endothelial growth factor (VEGF). Whilst these options demonstrate modest clinical benefits, none is yet to fully attenuate clinical progression or reverse damage to the retina. This has led to an interest in developing novel therapies for the condition, such as mediators of angiopoietin signaling axes, immunosuppressants, nonsteroidal anti-inflammatory drugs (NSAIDs), oxidative stress inhibitors and vitriol viscosity inhibitors. Further, preclinical research suggests that gene therapy treatment for DR could provide significant benefits over existing treatments options. AREAS COVERED: Here we review the pathophysiology of DR and provide an overview of currently available treatments. We then outline recent advances made towards improved patient outcomes and highlight the potential of the gene therapy paradigm to revolutionize DR management. EXPERT OPINION: Whilst significant progress has been made towards our understanding of DR, further research is required to enable the development of a detailed spatiotemporal model of the disease. In addition, we hope that improvements in our knowledge of the condition facilitate therapeutic innovations that continue to address unmet medical need and improve patient outcomes, with a focus on the development of targeted medicines.Cambridge Eye Trust Research Councils UK - Medical Research Council the Wellcome Trus

Is there evidence of selection in the dopamine receptor D4 gene in Australian invasive starling populations?

 Although population genetic theory is largely based on the premise that loci under study are selectively neutral, it has been acknowledged that the study of DNA sequence data under the influence of selection can be useful. In some circumstances, these loci show increased population differentiation and gene diversity. Highly polymorphic loci may be especially useful when studying populations having low levels of diversity overall, such as is often the case with threatened or newly established invasive populations. Using common starlings Sturnus vulgaris sampled from invasive Australian populations, we investigated sequence data of the dopamine receptor D4 gene (DRD4), a locus suspected to be under selection for novelty-seeking behaviour in a range of taxa including humans and passerine birds. We hypothesised that such behaviour may be advantageous when species encounter novel environments, such as during invasion. In addition to analyses to detect the presence of selection, we also estimated population differentiation and gene diversity using DRD4 data and compared these estimates to those from microsatellite and mitochondrial DNA sequence data, using the same individuals. We found little evidence for selection on DRD4 in starlings. However, we did find elevated levels of within-population gene diversity when compared to microsatellites and mitochondrial DNA sequence, as well as a greater degree of population differentiation. We suggest that sequence data from putatively nonneutral loci are a useful addition to studies of invasive populations, where low genetic variability is expected

Angiopoietins in Diabetic Retinopathy: Current Understanding and Therapeutic Potential.

Diabetic retinopathy (DR) is the commonest cause of blindness in the working-age population of the developed world. The molecular pathophysiology of DR is complex, and a complete spatiotemporal model of the disease is still being elucidated. Recently, a role for angiopoietin (Ang) proteins in the pathophysiology of DR has been proposed by several research groups, and several aspects of Ang signalling are being explored as novel therapeutic strategies. Here, we review the role of the Ang proteins in two important forms of DR, diabetic macular oedema and proliferative diabetic retinopathy. The function of the Ang proteins in regulating blood vessel permeability and neovascularisation is discussed, and we also evaluate recent preclinical and clinical studies highlighting the potential benefits of modulating Ang signalling as a treatment for DR.MW and PYWM are funded by Medical Research Council (UK) grants. MW, PYWM and AO 386 receive support from The Novo Nordisk UK Research Foundation, the Cambridge Eye Trust and 387 the Jukes Glaucoma Research Fund. AO, PYWM and KRM also hold Fight for Sight (UK) awards. 388 PYWM is also supported by a Clinician Scientist Fellowship Award (G1002570), the Isaac Newton 389 Trust, the UK National Institute of Health Research (NIHR) as part of the Rare Diseases 390 Translational Research Collaboration, and the NIHR Biomedical Research Centre based at 391 Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology. Research in 392 the laboratory is supported by core funding from Wellcome and MRC to the Wellcome-MRC 393 Cambridge Stem Cell Institute.Peer Reviewe

Immunobiology of a rationally-designed AAV2 capsid following intravitreal delivery in mice

Adeno-associated virus serotype 2 (AAV2) is a viral vector that can be used to deliver therapeutic genes to diseased cells in the retina. One strategy for altering AAV2 vectors involves the mutation of phosphodegron residues, which are thought to be phosphorylated/ubiquitinated in the cytosol, facilitating degradation of the vector and the inhibition of transduction. As such, mutation of phosphodegron residues have been correlated with increased transduction of target cells, however, an assessment of the immunobiology of wild-type and phosphodegron mutant AAV2 vectors following intravitreal (IVT) delivery to immunocompetent animals is lacking in the current literature. In this study, we show that IVT of a triple phosphodegron mutant AAV2 capsid is associated with higher levels of humoral immune activation, infiltration of CD4 and CD8 T-cells into the retina, generation of splenic germinal centre reactions, activation of conventional dendritic cell subsets, and elevated retinal gliosis compared to wild-type AAV2 capsids. However, we did not detect significant changes in electroretinography arising after vector administration. We also demonstrate that the triple AAV2 mutant capsid is less susceptible to neutralisation by soluble heparan sulphate and anti-AAV2 neutralising antibodies, highlighting a possible utility for the vector in terms of circumventing pre-existing humoral immunity. In summary, the present study highlights novel aspects of rationally-designed vector immunobiology, which may be relevant to their application in preclinical and clinical settings

Several types of types in programming languages

Types are an important part of any modern programming language, but we often forget that the concept of type we understand nowadays is not the same it was perceived in the sixties. Moreover, we conflate the concept of "type" in programming languages with the concept of the same name in mathematical logic, an identification that is only the result of the convergence of two different paths, which started apart with different aims. The paper will present several remarks (some historical, some of more conceptual character) on the subject, as a basis for a further investigation. The thesis we will argue is that there are three different characters at play in programming languages, all of them now called types: the technical concept used in language design to guide implementation; the general abstraction mechanism used as a modelling tool; the classifying tool inherited from mathematical logic. We will suggest three possible dates ad quem for their presence in the programming language literature, suggesting that the emergence of the concept of type in computer science is relatively independent from the logical tradition, until the Curry-Howard isomorphism will make an explicit bridge between them.Comment: History and Philosophy of Computing, HAPOC 2015. To appear in LNC

Mapping Valley Bottom Confinement at the Network Scale

In this article, we demonstrate the application of a continuous confinement metric across entire river networks. Confinement is a useful metric for characterizing and discriminating valley setting. At the reach scale, valley bottom confinement is measured and quantified as the ratio of the length of channel confined on either bank by a confining margin divided by the reach length. The valley bottom is occupied by the contemporary floodplain and/or its channel(s); confining margins can be any landform or feature that makes up the valley bottom margin, such as bedrock hillslopes, terraces, fans, or anthropogenic features such as stopbanks or constructed levees. To test the reliability of calculating confinement across entire networks, we applied our geoprocessing scripts across four physiographically distinct watersheds of the Pacific Northwest, USA using freely available national datasets. Comparison of manually digitized and mapped with modeled calculations of confinement revealed that roughly one‐third of reaches were equivalent and about two‐thirds of the sites differ by less than ±15%. A sensitivity analysis found that a 500 m reach segmentation length produced reasonable agreement with manual, categorical, expert‐derived analysis of confinement. Confinement accuracy can be improved (c. 4% to 17% gains) using a more accurately mapped valley bottom and channel position (i.e. with higher‐resolution model inputs). This is particularly important when differentiating rivers in the partly confined valley setting. However, at the watershed scale, patterns derived from mapping confinement are not fundamentally different, making this a reasonably accurate and rapid technique for analysis and measurement of confinement across broad spatial extents

Doing gender locally: The importance of ‘place’ in understanding marginalised masculinities and young men’s transitions to ‘safe’ and successful futures

Observable anxieties have been developing about the position of boys and young men in contemporary society in recent years. This is expressed as a crisis of masculinity, in which place is often implicitly implicated, but is rarely considered for its role in the shaping of young men’s practices, trajectories and aspirations. Drawing on research conducted with young people who accessed a range of social care support services, this article argues that transition means different things for young men in different locales and that local definitions of masculinity are required to better understand young men’s lives and the opportunities available to them. The authors argue that home life, street life, individual neighbourhoods, regions and nations all shaped the young men’s identities and the practices they (and the staff working with them) drew on in order to create successful futures and ‘safe’ forms of masculinity. It is suggested that this place-based approach has the potential to re-shape the ‘crisis’ discourse surrounding masculinity and the anxieties associated with young men

Fluctuations and differential contraction during regeneration of Hydra vulgaris tissue toroids

We studied regenerating bilayered tissue toroids dissected from Hydra vulgaris polyps and relate our macroscopic observations to the dynamics of force-generating mesoscopic cytoskeletal structures. Tissue fragments undergo a specific toroid-spheroid folding process leading to complete regeneration towards a new organism. The time scale of folding is too fast for biochemical signalling or morphogenetic gradients which forced us to assume purely mechanical self-organization. The initial pattern selection dynamics was studied by embedding toroids into hydro-gels allowing us to observe the deformation modes over longer periods of time. We found increasing mechanical fluctuations which break the toroidal symmetry and discuss the evolution of their power spectra for various gel stiffnesses. Our observations are related to single cell studies which explain the mechanical feasibility of the folding process. In addition, we observed switching of cells from a tissue bound to a migrating state after folding failure as well as in tissue injury. We found a supra-cellular actin ring assembled along the toroid's inner edge. Its contraction can lead to the observed folding dynamics as we could confirm by finite element simulations. This actin ring in the inner cell layer is assembled by myosin- driven length fluctuations of supra-cellular {\alpha}-actin structures (myonemes) in the outer cell-layer.Comment: 19 pages and 8 figures, submitted to New Journal of Physic

Spatial variation in the fine-structure constant -- new results from VLT/UVES

(abridged) We present a new analysis of a large sample of quasar absorption-line spectra obtained using UVES (the Ultraviolet and Visual Echelle Spectrograph) on the VLT (Very Large Telescope) in Chile. In the VLT sample (154 absorbers), we find evidence that alpha increases with increasing cosmological distance from Earth. However, as previously shown, the Keck sample (141 absorbers) provided evidence for a smaller alpha in the distant absorption clouds. Upon combining the samples an apparent variation of alpha across the sky emerges which is well represented by an angular dipole model pointing in the direction RA=(17.3 +/- 1.0) hr, dec. = (-61 +/- 10) deg, with amplitude (0.97 +0.22/-0.20) x 10^(-5). The dipole model is required at the 4.1 sigma statistical significance level over a simple monopole model where alpha is the same across the sky (but possibly different to the current laboratory value). The data sets reveal a number of remarkable consistencies: various data cuts are consistent and there is consistency in the overlap region of the Keck and VLT samples. Assuming a dipole-only (i.e. no-monopole) model whose amplitude grows proportionally with `lookback-time distance' (r=ct, where t is the lookback time), the amplitude is (1.1 +/- 0.2) x 10^(-6) GLyr^(-1) and the model is significant at the 4.2 sigma confidence level over the null model [Delta alpha]/alpha = 0). We apply robustness checks and demonstrate that the dipole effect does not originate from a small subset of the absorbers or spectra. We present an analysis of systematic effects, and are unable to identify any single systematic effect which can emulate the observed variation in alpha.Comment: 47 pages, 35 figures. Accepted for publication by Monthly Notices of the Royal Astronomical Society. Please see http://astronomy.swin.edu.au/~mmurphy/pub.html for an ASCII version of table A1 and the full set of Voigt profile fits for appendix