194 research outputs found

    Spatio-temporal atlas of bone mineral density ageing

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    Osteoporosis is an age-associated bone disease characterised by low bone mass. An improved understanding of the underlying mechanism for age-related bone loss could lead to enhanced preventive and therapeutic strategies for osteoporosis. In this work, we propose a fully automatic pipeline for developing a spatio-temporal atlas of ageing bone. Bone maps are collected using a dual-energy X-ray absorptiometry (DXA) scanner. Each scan is then warped into a reference template to eliminate morphological variation and establish a correspondence between pixel coordinates. Pixel-wise bone density evolution with ageing was modelled using smooth quantile curves. To construct the atlas, we amalgamated a cohort of 1714 Caucasian women (20–87 years) from five different centres in North Western Europe. As a systematic difference exists between different DXA manufacturers, we propose a novel calibration technique to homogenise bone density measurements across the centres. This technique utilises an alternating minimisation technique to map the observed bone density measurements into a latent standardised space. To the best of our knowledge, this is the first spatio-temporal atlas of ageing bone

    Generalised Player Modelling : Why Artificial Intelligence in Games Should Incorporate Meaning, with a Formalism for so Doing

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    General game-playing artificial intelligence (AI) has recently seen important advances due to the various techniques known as ‘deep learning’. However, in terms of human-computer interaction, the advances conceal a major limitation: these algorithms do not incorporate any sense of what human players find meaningful in games. I argue that adaptive game AI will be enhanced by a generalised player model, because games are inherently human artefacts which require some encoding of the human perspective in order to respond naturally to individual players. The player model provides constraints on the adaptive AI, which allow it to encode aspects of what human players find meaningful. I propose that a general player model requires parameters for the subjective experience of play, including: player psychology, game structure, and actions of play. I argue that such a player model would enhance efficiency of per-game solutions, and also support study of game-playing by allowing (within-player) comparison between games, or (within-game) comparison between players (human and AI). Here we detail requirements for functional adaptive AI, arguing from first-principles drawn from games research literature, and propose a formal specification for a generalised player model based on our ‘Behavlets’ method for psychologically-derived player modelling.Peer reviewe

    At work and play; business events as entrepreneurial spaces

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    There is inadequate literature examining, and illustrating, the integration of play and business events and how this facilitates entrepreneurial opportunities. Business events are distinct from the patterns of ordinary life and increasingly offer participants an ‘invitation to play’, encouraging socialization and trust. This article examines the role of play in the design of business events and how this can enable entrepreneurial outcomes. Through examination of diverse, but related, literature and three contrasting, empirically based, case studies, this article illustrates how event creators take an increasingly entrepreneurial approach. These cases range from a charity event with participants sleeping with the homeless on a city’s streets, a major flooring manufacturer designing events to outsource innovation and an imaginative event activity termed ‘coffee and papers’. Designing events that fuse, rather than polarize, play and work enables business event settings, and activities, which trigger entrepreneurial outcomes. This article adds to the embryonic literature and concludes by identifying four principles that underlie the effectual facilitation of play in a business event setting

    Diagnostic reliability of magnetic resonance imaging for central nervous system syndromes in systemic lupus erythematosus: a prospective cohort study

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    <p>Abstract</p> <p>Background</p> <p>Previous studies of magnetic resonance imaging (MRI) as a diagnostic tool for central nervous system (CNS) syndromes in systemic lupus erythematosus (SLE) contained several limitations such as study design, number of enrolled patients, and definition of CNS syndromes. We overcame these problems and statistically evaluated the diagnostic values of abnormal MRI signals and their chronological changes in CNS syndromes of SLE.</p> <p>Methods</p> <p>We prospectively studied 191 patients with SLE, comparing those with (n = 57) and without (n = 134) CNS syndrome. CNS syndromes were characterized using the American College of Rheumatology case definitions.</p> <p>Results</p> <p>Any abnormal MRI signals were more frequently observed in subjects in the CNS group (n = 25) than in the non-CNS group (n = 32) [relative risk (RR), 1.7; 95% confidence interval (CI), 1.1-2.7; <it>p </it>= 0.016] and the positive and negative predictive values for the diagnosis of CNS syndrome were 42% and 76%, respectively. Large abnormal MRI signals (ø ≥ 10 mm) were seen only in the CNS group (n = 7; RR, 3.7; CI, 2.9-4.7; <it>p </it>= 0.0002), whereas small abnormal MRI signals (ø < 10 mm) were seen in both groups with no statistical difference. Large signals always paralleled clinical outcome (<it>p </it>= 0.029), whereas small signals did not (<it>p </it>= 1.000).</p> <p>Conclusions</p> <p>Abnormal MRI signals, which showed statistical associations with CNS syndrome, had insufficient diagnostic values. A large MRI signal was, however, useful as a diagnostic and surrogate marker for CNS syndrome of SLE, although it was less common.</p

    Tumor Necrosis Factor-α +489G/A gene polymorphism is associated with chronic obstructive pulmonary disease

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    BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by a chronic inflammatory process, in which the pro-inflammatory cytokine Tumor Necrosis Factor (TNF)-α is considered to play a role. In the present study the putative involvement of TNF-α gene polymorphisms in pathogenesis of COPD was studied by analysis of four TNF-α gene polymorphisms in a Caucasian COPD population. METHODS: TNF-α gene polymorphisms at positions -376G/A, -308G/A, -238G/A, and +489G/A were examined in 169 Dutch COPD patients, who had a mean forced expiratory volume in one second (FEV1) of 37 ± 13%, and compared with a Dutch population control group of 358 subjects. RESULTS: The data showed that the TNF-α +489G/A genotype frequency tended to be different in COPD patients as compared to population controls, which was due to an enhanced frequency of the GA genotype. In line herewith, carriership of the minor allele was associated with enhanced risk of development of COPD (odds ratio = 1.9, p = 0.009). The other TNF-α gene polymorphisms studied revealed no discrimination between patients and controls. No differences in the examined four TNF-α polymorphisms were found between subtypes of COPD, which were stratified for the presence of radiological emphysema. However, comparison of the COPD subtypes with controls showed a significant difference in the TNF-α +489G/A genotype in patients without radiological emphysema (χ(2)-test: p < 0.025 [Bonferroni adjusted]), while no differences between COPD patients with radiological emphysema and controls were observed. CONCLUSION: Based on the reported data, it is concluded that COPD, and especially a subgroup of COPD patients without radiological emphysema, is associated with TNF-α +489G/A gene polymorphism

    Anti-CCP2 Antibodies: An Overview and Perspective of the Diagnostic Abilities of this Serological Marker for Early Rheumatoid Arthritis

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    The literature of the last 4 years confirms that the anti-CCP2 test is a very useful marker for the early and specific diagnosis of rheumatoid arthritis (RA). The anti-CCP2 test is very specific for RA (95–99%) and has sensitivity comparable to that of the rheumatoid factor (70–75%). The antibodies can be detected very early in the disease and can be used as an indicator for the progression and prognosis of RA. In this review, these interesting properties and some future possibilities of this diagnostic test are discussed

    Competition for FcRn-mediated transport gives rise to short half-life of human IgG3 and offers therapeutic potential

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    Human IgG3 displays the strongest effector functions of all IgG subclasses but has a short half-life for unresolved reasons. Here we show that IgG3 binds to IgG-salvage receptor (FcRn), but that FcRn-mediated transport and rescue of IgG3 is inhibited in the presence of IgG1 due to intracellular competition between IgG1 and IgG3. We reveal that this occurs because of a single amino acid difference at position 435, where IgG3 has an arginine instead of the histidine found in all other IgG subclasses. While the presence of R435 in IgG increases binding to FcRn at neutral pH, it decreases binding at acidic pH, affecting the rescue efficiency—but only in the presence of H435–IgG. Importantly, we show that in humans the half-life of the H435-containing IgG3 allotype is comparable to IgG1. H435–IgG3 also gave enhanced protection against a pneumococcal challenge in mice, demonstrating H435–IgG3 to be a candidate for monoclonal antibody therapies
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