64 research outputs found

    Prism adaptation to rightward optical deviation improves postural imbalance in left-hemiparetic patients

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    AbstractLeft-hemiparetic patients show predominant postural imbalance as compared to right-hemiparetic patients. The right hemisphere is crucial for generating internal maps used for perceptual and premotor processing of spatial information. Predominant postural imbalance with right-brain damage could thus result from a distortion of an internal postural map. Well-known manifestations of distorted internal maps due to right-hemisphere lesions, such as hemineglect, may show improvement following prism adaptation shifting the visual field to the right. We therefore investigated the effect of prism adaptation on postural imbalance in left-hemiparetic patients. Three groups of five patients were either adapted to prisms deviating the visual field to the right or left or exposed to neutral prisms while performing reaching movements of the right arm. Postural imbalance was reduced only following prism adaptation to the right. Thus, brief adaptation (i.e., 3 min) to rightward-shifting prisms can dramatically improve postural imbalance. This result shows that the effect of exposure to prisms that horizontally shift the visual field to the right in a reaching task generalizes to the postural system, and it suggests an interaction between horizontal and vertical reference frames. This also supports the theory that predominant postural imbalance in patients with right-brain damage may be partly related to a distortion of an internal postural map

    In vitro and in vivo evaluation of a dextran-graft-polybutylmethacrylate copolymer coated on CoCr metallic stent

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    International audienceIntroduction: The major complications of stent implantation are restenosis and late stent thrombosis. PBMA polymers are used for stent coating because of their mechanical properties. We previously synthesized and characterized Dextrangraft-polybutylmethacrylate copolymer (Dex-PBMA) as a potential stent coating. In this study, we evaluated the haemocompatibility and biocompatibility properties of Dex-PBMA in vitro and in vivo.Methods: Here, we investigated: (1) the effectiveness of polymer coating under physiological conditions and its ability to release Tacrolimus®, (2) the capacity of Dex-PBMA to inhibit Staphylococcus aureus adhesion, (3) the thrombin generation and the human platelet adhesion in static and dynamic conditions, (4) thebiocompatibility properties in vitro on human endothelial colony forming cells (ECFC) and on mesenchymal stem cells (MSC) and in vivo in rat models, and (5) we implanted Dex-PBMA and Dex-PBMA TAC coated stents in neointimal hyperplasia restenosis rabbit model. Results: Dex-PBMA coating efficiently prevented bacterial adhesion and release Tacrolimus®. Dex-PBMA exhibit haemocompatibility properties under flow and ECFC and MSC compatibility. In vivo, no pathological foreign body reaction was observed neither after intramuscular nor intravascular aortic implantation. After Dex-PBMA and Dex-PBMATAC coated stents 30 days implantation in a restenosis rabbit model, an endothelial cell coverage was observed and the lumenpatency was preserved.Conclusion: Based on our findings, Dex-PBMA exhibited vascular compatibility and can potentially be used as a coating for metallic coronary stents

    Water, sanitation and hygiene for the prevention of diarrhoea

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    Background Ever since John Snow’s intervention on the Broad St pump, the effect of water quality, hygiene and sanitation in preventing diarrhoea deaths has always been debated. The evidence identified in previous reviews is of variable quality, and mostly relates to morbidity rather than mortality

    Interactive Language Learning by Robots: The Transition from Babbling to Word Forms

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    The advent of humanoid robots has enabled a new approach to investigating the acquisition of language, and we report on the development of robots able to acquire rudimentary linguistic skills. Our work focuses on early stages analogous to some characteristics of a human child of about 6 to 14 months, the transition from babbling to first word forms. We investigate one mechanism among many that may contribute to this process, a key factor being the sensitivity of learners to the statistical distribution of linguistic elements. As well as being necessary for learning word meanings, the acquisition of anchor word forms facilitates the segmentation of an acoustic stream through other mechanisms. In our experiments some salient one-syllable word forms are learnt by a humanoid robot in real-time interactions with naive participants. Words emerge from random syllabic babble through a learning process based on a dialogue between the robot and the human participant, whose speech is perceived by the robot as a stream of phonemes. Numerous ways of representing the speech as syllabic segments are possible. Furthermore, the pronunciation of many words in spontaneous speech is variable. However, in line with research elsewhere, we observe that salient content words are more likely than function words to have consistent canonical representations; thus their relative frequency increases, as does their influence on the learner. Variable pronunciation may contribute to early word form acquisition. The importance of contingent interaction in real-time between teacher and learner is reflected by a reinforcement process, with variable success. The examination of individual cases may be more informative than group results. Nevertheless, word forms are usually produced by the robot after a few minutes of dialogue, employing a simple, real-time, frequency dependent mechanism. This work shows the potential of human-robot interaction systems in studies of the dynamics of early language acquisition

    Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis

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    Chronic mucocutaneous candidiasis disease (CMCD) may be caused by autosomal dominant (AD) IL-17F deficiency or autosomal recessive (AR) IL-17RA deficiency. Here, using whole-exome sequencing, we identified heterozygous germline mutations in STAT1 in 47 patients from 20 kindreds with AD CMCD. Previously described heterozygous STAT1 mutant alleles are loss-of-function and cause AD predisposition to mycobacterial disease caused by impaired STAT1-dependent cellular responses to IFN-γ. Other loss-of-function STAT1 alleles cause AR predisposition to intracellular bacterial and viral diseases, caused by impaired STAT1-dependent responses to IFN-α/β, IFN-γ, IFN-λ, and IL-27. In contrast, the 12 AD CMCD-inducing STAT1 mutant alleles described here are gain-of-function and increase STAT1-dependent cellular responses to these cytokines, and to cytokines that predominantly activate STAT3, such as IL-6 and IL-21. All of these mutations affect the coiled-coil domain and impair the nuclear dephosphorylation of activated STAT1, accounting for their gain-of-function and dominance. Stronger cellular responses to the STAT1-dependent IL-17 inhibitors IFN-α/β, IFN-γ, and IL-27, and stronger STAT1 activation in response to the STAT3-dependent IL-17 inducers IL-6 and IL-21, hinder the development of T cells producing IL-17A, IL-17F, and IL-22. Gain-of-function STAT1 alleles therefore cause AD CMCD by impairing IL-17 immunity

    Human IFN-γ immunity to mycobacteria is governed by both IL-12 and IL-23

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    Hundreds of patients with autosomal recessive, complete IL-12p40 or IL-12Rß1 deficiency have been diagnosed over the last 20 years. They typically suffer from invasive mycobacteriosis and, occasionally, from mucocutaneous candidiasis. Susceptibility to these infections is thought to be due to impairments of IL- 12–dependent IFN-? immunity and IL-23–dependent IL-17A/IL-17F immunity, respectively. We report here patients with autosomal recessive, complete IL- 12Rß2 or IL-23R deficiency, lacking responses to IL-12 or IL- 23 only, all of whom, unexpectedly, display mycobacteriosis without candidiasis. We show that aß T, ?d T, B, NK, ILC1, and ILC2 cells from healthy donors preferentially produce IFN-? in response to IL-12, whereas NKT cells and MAIT cells preferentially produce IFN-? in response to IL-23. We also show that the development of IFN-?–producing CD4+ T cells, including, in particular, mycobacterium-specific TH1* cells (CD45RA-CCR6+), is dependent on both IL-12 and IL-23. Last, we show that IL12RB1, IL12RB2, and IL23R have similar frequencies of deleterious variants in the general population. The comparative rarity of symptomatic patients with IL-12Rß2 or IL-23R deficiency, relative to IL-12Rß1 deficiency, is, therefore, due to lower clinical penetrance. There are fewer symptomatic IL-23R– and IL-12Rß2–deficient than IL-12Rß1–deficient patients, not because these genetic disorders are rarer, but because the isolated absence of IL-12 or IL-23 is, in part, compensated by the other cytokine for the production of IFN-?, thereby providing some protection against mycobacteria. These experiments of nature show that human IL-12 and IL-23 are both required for optimal IFN-?–dependent immunity to mycobacteria, both individually and much more so cooperatively

    Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

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    Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries
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