89 research outputs found

    On Semi-Algebraic Proofs and Algorithms

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    An artificial intelligence algorithm is highly accurate for detecting endoscopic features of eosinophilic esophagitis

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    The endoscopic features associated with eosinophilic esophagitis (EoE) may be missed during routine endoscopy. We aimed to develop and evaluate an Artificial Intelligence (AI) algorithm for detecting and quantifying the endoscopic features of EoE in white light images, supplemented by the EoE Endoscopic Reference Score (EREFS). An AI algorithm (AI-EoE) was constructed and trained to differentiate between EoE and normal esophagus using endoscopic white light images extracted from the database of the University Hospital Augsburg. In addition to binary classification, a second algorithm was trained with specific auxiliary branches for each EREFS feature (AI-EoE-EREFS). The AI algorithms were evaluated on an external data set from the University of North Carolina, Chapel Hill (UNC), and compared with the performance of human endoscopists with varying levels of experience. The overall sensitivity, specificity, and accuracy of AI-EoE were 0.93 for all measures, while the AUC was 0.986. With additional auxiliary branches for the EREFS categories, the AI algorithm (AI-EoE-EREFS) performance improved to 0.96, 0.94, 0.95, and 0.992 for sensitivity, specificity, accuracy, and AUC, respectively. AI-EoE and AI-EoE-EREFS performed significantly better than endoscopy beginners and senior fellows on the same set of images. An AI algorithm can be trained to detect and quantify endoscopic features of EoE with excellent performance scores. The addition of the EREFS criteria improved the performance of the AI algorithm, which performed significantly better than endoscopists with a lower or medium experience level

    Mechanism of action of novel NO-releasing furoxan derivatives of aspirin in human platelets

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    1. Incorporation of a nitric oxide (NO)-releasing moiety in aspirin can overcome its gastric side effects. 2. We investigated the NO-release patterns and antiplatelet effects of novel furoxan derivatives of aspirin (B8 and B7) in comparison to existing antiplatelet agents. 3. Cyclooxygenase (COX) activity was investigated in purified enzyme using an electron paramagnetic resonance-based technique. Concentration–response curves for antiplatelet agents±the soluble guanylate cyclase inhibitor, ODQ (50 μM) were generated in platelet-rich plasma (PRP) and washed platelets (WP) activated with collagen using turbidometric aggregometry. NO was detected using an isolated NO electrode. 4. The furoxan derivatives of aspirin (B8, B7) and their NO-free furazan equivalents (B16, B15; all 100 μM) significantly inhibited COX activity (P<0.01; n=6) in vitro and caused aspirin-independent, cGMP-dependent inhibition of collagen-induced platelet aggregation in WP. B8 was more potent than B7 (PRP IC(50)=0.62±0.1 μM for B8; 400±89 μM for B7; P<0.0001. WP IC(50)s=0.6±0.1 and 62±10 μM, respectively). The NO-free furazan counterparts were less potent antiplatelet agents (WP IC(50)s=54±3 μM and 62±10 μM, respectively; P<0.0001, B8 vs B16). Of the hybrids investigated, only B8 retained antiplatelet activity in PRP. 5. NO release from furoxan–aspirin hybrids was undetectable in buffer alone, but was accelerated in the presence of either plasma or plasma components, albumin (4%), glutathione (GSH; 3 μM) and ascorbate (50 μM), the effects of which were additive for B7 but not B8. NO generation from furoxans was greatly enhanced by platelet extract, an effect that could largely be explained by the synergistic effect of intracellular concentrations of GSH (3 mM) and ascorbate (1 mM). 6. We conclude that the decomposition of furoxan–aspirin hybrids to generate biologically active NO is catalysed by endogenous agents which may instil a potential for primarily intracellular delivery of NO. The blunting of the aspirin effects of furoxan hybrids is likely to be due to loss of the acetyl moiety in plasma; the observed antiplatelet effects are thereby primarily mediated via NO release. Compounds of this class might represent a novel means of inhibiting platelet aggregation by a combination of NO generation and COX inhibition

    Chemosensory Cues to Conspecific Emotional Stress Activate Amygdala in Humans

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    Alarm substances are airborne chemical signals, released by an individual into the environment, which communicate emotional stress between conspecifics. Here we tested whether humans, like other mammals, are able to detect emotional stress in others by chemosensory cues. Sweat samples collected from individuals undergoing an acute emotional stressor, with exercise as a control, were pooled and presented to a separate group of participants (blind to condition) during four experiments. In an fMRI experiment and its replication, we showed that scanned participants showed amygdala activation in response to samples obtained from donors undergoing an emotional, but not physical, stressor. An odor-discrimination experiment suggested the effect was primarily due to emotional, and not odor, differences between the two stimuli. A fourth experiment investigated behavioral effects, demonstrating that stress samples sharpened emotion-perception of ambiguous facial stimuli. Together, our findings suggest human chemosensory signaling of emotional stress, with neurobiological and behavioral effects

    Adaptive Radiation in Mediterranean Cistus (Cistaceae)

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    lineage consists of 12 species primarily distributed in Mediterranean habitats and is herein subject to analysis. lineages), which display asymmetric characteristics: number of species (2 vs. 10), leaf morphologies (linear vs. linear to ovate), floral characteristics (small, three-sepalled vs. small to large, three- or five-sepalled flowers) and ecological attributes (low-land vs. low-land to mountain environments). A positive phenotype-environment correlation has been detected by historical reconstructions of morphological traits (leaf shape, leaf labdanum content and leaf pubescence). Ecological evidence indicates that modifications of leaf shape and size, coupled with differences in labdanum secretion and pubescence density, appear to be related to success of new species in different Mediterranean habitats.

    5-Lipoxygenase Metabolic Contributions to NSAID-Induced Organ Toxicity

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    Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

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    BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

    A computer simulation of solidification taking into account the movement of the liquid phase

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    In the paper, we present the results of solidification simulation taking into account the movement of the liquid phase. The results are obtained from an author software which is implemented on the base of a stabilized finite elements method (Petrov-Galerkin formulation). Using that formulation the Navier-Stokes equation is solved together with the convection term (Boussinesq approximation). The Finite Element Method (FEM) formulation is responsible for solidification, approximating the solution of the heat conduction equation (with the internal heat source term responsible for the heat released during the phase transition). The movement of the liquid phase in a solidifying cast that is caused by convection can significantly affect the process of heat transfer from the casting to the mold, which in turn has an influence on the temperature distribution in the cast and may cause a change in the location of the defects. The presented results allow to assess under what conditions the effect of convection on the solidification process is significant

    A computer simulation of solidification taking into account the movement of the liquid phase

    No full text
    In the paper, we present the results of solidification simulation taking into account the movement of the liquid phase. The results are obtained from an author software which is implemented on the base of a stabilized finite elements method (Petrov-Galerkin formulation). Using that formulation the Navier-Stokes equation is solved together with the convection term (Boussinesq approximation). The Finite Element Method (FEM) formulation is responsible for solidification, approximating the solution of the heat conduction equation (with the internal heat source term responsible for the heat released during the phase transition). The movement of the liquid phase in a solidifying cast that is caused by convection can significantly affect the process of heat transfer from the casting to the mold, which in turn has an influence on the temperature distribution in the cast and may cause a change in the location of the defects. The presented results allow to assess under what conditions the effect of convection on the solidification process is significant
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