708 research outputs found

    Improving engagement of stroke survivors using desktop virtual Reality-Based serious games for upper limb rehabilitation: A multiple case study

    Get PDF
    Engagement with upper limb rehabilitation post-stroke can improve rehabilitation outcomes. Virtual Reality can be used to make rehabilitation more engaging. In this paper, we propose a multiple case study to determine: (1) whether game design principles (identified in an earlier study as being likely to engage) actually do engage, in practice, a sample of stroke survivors with a Desktop Virtual Reality-based Serious Game designed for upper limb rehabilitation; and (2) what game design factors support the existence of these principles in the game. In this study, we considered 15 principles: awareness , feedback , interactivity , flow , challenge , attention , interest , involvement , psychological absorption , motivation , effort , clear instructions , usability , purpose , and a first-person view . Four stroke survivors used, for a period of 12 weeks, a Virtual Reality-based upper limb rehabilitation system called the Neuromender Rehabilitation System. The stroke survivors were then asked how well each of the 15 principles was supported by the Neuromender Rehabilitation System and how much they felt each principle supported their engagement with the system. All the 15 tested principles had good or reasonable support from the participants as being engaging. Use of feedback was emphasised as an important design factor for supporting the design principles, but there was otherwise little agreement in important design factors among the participants. This indicates that more personalised experiences may be necessary for optimised engagement. The insight gained can be used to inform the design of a larger scale statistical study into what engages stroke survivors with Desktop Virtual Reality-based upper limb rehabilitation

    GJ 9404 b:A Confirmed Eccentric Planet, and not a Candidate

    Get PDF
    Eccentric orbits can be decomposed into a series of sine curves which affects how the false alarm probability is computed when using traditional periodograms on radial-velocity data. Here we show that a candidate exoplanet orbiting the M dwarf GJ 9404, identified by the HADES survey using data from the HARPS-N spectrograph, is in fact a bona-fide planet on a highly eccentric orbit. Far from a candidate, GJ 9404 b is detected with a high confidence. We reach our conclusion using two methods that assume Keplerian functions rather than sines to compute a detection probability, a Bayes Factor, and the FIP periodogram. We compute these using nested sampling with {\tt kima}.Comment: 3 pages, 1 figur

    CHCHD4 regulates tumour proliferation and EMT-related phenotypes, through respiratory chain-mediated metabolism

    Get PDF
    Abstract: Background: Mitochondrial oxidative phosphorylation (OXPHOS) via the respiratory chain is required for the maintenance of tumour cell proliferation and regulation of epithelial to mesenchymal transition (EMT)-related phenotypes through mechanisms that are not fully understood. The essential mitochondrial import protein coiled-coil helix coiled-coil helix domain-containing protein 4 (CHCHD4) controls respiratory chain complex activity and oxygen consumption, and regulates the growth of tumours in vivo. In this study, we interrogate the importance of CHCHD4-regulated mitochondrial metabolism for tumour cell proliferation and EMT-related phenotypes, and elucidate key pathways involved. Results: Using in silico analyses of 967 tumour cell lines, and tumours from different cancer patient cohorts, we show that CHCHD4 expression positively correlates with OXPHOS and proliferative pathways including the mTORC1 signalling pathway. We show that CHCHD4 expression significantly correlates with the doubling time of a range of tumour cell lines, and that CHCHD4-mediated tumour cell growth and mTORC1 signalling is coupled to respiratory chain complex I (CI) activity. Using global metabolomics analysis, we show that CHCHD4 regulates amino acid metabolism, and that CHCHD4-mediated tumour cell growth is dependent on glutamine. We show that CHCHD4-mediated tumour cell growth is linked to CI-regulated mTORC1 signalling and amino acid metabolism. Finally, we show that CHCHD4 expression in tumours is inversely correlated with EMT-related gene expression, and that increased CHCHD4 expression in tumour cells modulates EMT-related phenotypes. Conclusions: CHCHD4 drives tumour cell growth and activates mTORC1 signalling through its control of respiratory chain mediated metabolism and complex I biology, and also regulates EMT-related phenotypes of tumour cells

    Quantifying risks and interventions that have affected the burden of lower respiratory infections among children younger than 5 years: an analysis for the Global Burden of Disease Study 2017

    Get PDF
    Background Despite large reductions in under-5 lower respiratory infection (LRI) mortality in many locations, the pace of progress for LRIs has generally lagged behind that of other childhood infectious diseases. To better inform programmes and policies focused on preventing and treating LRIs, we assessed the contributions and patterns of risk factor attribution, intervention coverage, and sociodemographic development in 195 countries and territories by drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) LRI estimates. Methods We used four strategies to model LRI burden: the mortality due to LRIs was modelled using vital registration data, demographic surveillance data, and verbal autopsy data in a predictive ensemble modelling tool; the incidence of LRIs was modelled using population representative surveys, health-care utilisation data, and scientific literature in a compartmental meta-regression tool; the attribution of risk factors for LRI mortality was modelled in a counterfactual framework; and trends in LRI mortality were analysed applying changes in exposure to risk factors over time. In GBD, infectious disease mortality, including that due to LRI, is among HIV-negative individuals. We categorised locations based on their burden in 1990 to make comparisons in the changing burden between 1990 and 2017 and evaluate the relative percent change in mortality rate, incidence, and risk factor exposure to explain differences in the health loss associated with LRIs among children younger than 5 years. Findings In 2017, LRIs caused 808 920 deaths (95% uncertainty interval 747 286ā€“873 591) in children younger than 5 years. Since 1990, there has been a substantial decrease in the number of deaths (from 2 337 538 to 808 920 deaths; 65Ā·4% decrease, 61Ā·5ā€“68Ā·5) and in mortality rate (from 362Ā·7 deaths [330Ā·1ā€“392Ā·0] per 100 000 children to 118Ā·9 deaths [109Ā·8ā€“128Ā·3] per 100 000 children; 67Ā·2% decrease, 63Ā·5ā€“70Ā·1). LRI incidence declined globally (32Ā·4% decrease, 27Ā·2ā€“37Ā·5). The percent change in under-5 mortality rate and incidence has varied across locations. Among the risk factors assessed in this study, those responsible for the greatest decrease in under-5 LRI mortality between 1990 and 2017 were increased coverage of vaccination against Haemophilus influenza type b (11Ā·4% decrease, 0Ā·0ā€“24Ā·5), increased pneumococcal vaccine coverage (6Ā·3% decrease, 6Ā·1ā€“6Ā·3), and reductions in household air pollution (8Ā·4%, 6Ā·8ā€“9Ā·2). Interpretation Our findings show that there have been substantial but uneven declines in LRI mortality among countries between 1990 and 2017. Although improvements in indicators of sociodemographic development could explain some of these trends, changes in exposure to modifiable risk factors are related to the rates of decline in LRI mortality. No single intervention would universally accelerate reductions in health loss associated with LRIs in all settings, but emphasising the most dominant risk factors, particularly in countries with high case fatality, can contribute to the reduction of preventable deaths

    The Cortical Signature of Alzheimer's Disease: Regionally Specific Cortical Thinning Relates to Symptom Severity in Very Mild to Mild AD Dementia and is Detectable in Asymptomatic Amyloid-Positive Individuals

    Get PDF
    Alzheimer's disease (AD) is associated with neurodegeneration in vulnerable limbic and heteromodal regions of the cerebral cortex, detectable in vivo using magnetic resonance imaging. It is not clear whether abnormalities of cortical anatomy in AD can be reliably measured across different subject samples, how closely they track symptoms, and whether they are detectable prior to symptoms. An exploratory map of cortical thinning in mild AD was used to define regions of interest that were applied in a hypothesis-driven fashion to other subject samples. Results demonstrate a reliably quantifiable in vivo signature of abnormal cortical anatomy in AD, which parallels known regional vulnerability to AD neuropathology. Thinning in vulnerable cortical regions relates to symptom severity even in the earliest stages of clinical symptoms. Furthermore, subtle thinning is present in asymptomatic older controls with brain amyloid binding as detected with amyloid imaging. The reliability and clinical validity of AD-related cortical thinning suggests potential utility as an imaging biomarker. This ā€œdisease signatureā€ approach to cortical morphometry, in which disease effects are mapped across the cortical mantle and then used to define ROIs for hypothesis-driven analyses, may provide a powerful methodological framework for studies of neuropsychiatric diseases

    Towards a Critique of Educative Violence: Walter Benjamin and ā€˜Second Educationā€™

    Get PDF
    Although modern systems of mass education are typically defined in their opposition to violence, it has been argued that it is only through an insistent and critical focus upon violence that radical thought can be sustained. This article seeks to take up this challenge in relation to Walter Benjaminā€™s lesser-known writings on education. Benjamin retained throughout his life a deep suspicion about academic institutions and about the pedagogic, social and economic violence implicated in the idea of cultural transmission. He nonetheless remained committed to the possibility of another kind of revolutionary potential inherent to true education and, when he comes to speak of this in his Critique of Violence, it is remarkable that he describes it as manifesting an educative violence. This article argues that Benjaminā€™s philosophy works toward a critique of educative violence that results in a distinction between a ā€˜firstā€™ and ā€˜secondā€™ kind of education and asks whether destruction might have a positive role to play within pedagogical theories in contrast to current valorisations of creativity and productivity
    • ā€¦
    corecore