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Human speakers generally find it easy to refer to entities in such a way that their hearers can determine who or what is being talked about. In an attempt to model this behaviour, researchers in computational linguistics have explored the development of algorithms that operate in a deliberate manner, choosing attributes of an intended referent on the basis of their ability to distinguish that entity from its distractors. Psycholinguistic models, on the other hand, suggest that speakers align their referring expressions at several linguistic levels with those used previously in the discourse. This implies more subconscious reuse, and less deliberate choice, than is found in computational models of referring expression generation. Which of these is a more accurate characterisation of what people do? Do both models capture aspects of human referring behaviour? In this paper, we use a machine-learning approach to explore these questions. In our first study, we examine how underlying factors of the psycholinguistic and the computational models impact on the production of reference in dialogue. In our second study, we explore the psychological validity of another crucial aspect of some computational approaches to reference production: their serial dependency characteristic, whereby attributes are included in a referring expression based on which other attributes have already been chosen. The results of both studies suggest that the assumptions underpinning computational algorithms do not play a large role in people's referring behaviour. [ABSTRACT FROM AUTHOR]

Background Pulmonary arterial hypertension (PAH) is a progressive condition harboring a poor prognosis. Iron deficiency in PAH correlates with disease severity and mortality. While replacement therapy may be beneficial, dietary iron absorption is impaired in PAH patients by hepcidin, a key regulatory protein of iron homoeostasis. We therefore assessed the therapeutic potential and safety of intravenous iron supplementation in patients with PAH and iron deficiency. Methods 20 patients with PAH and iron deficiency, who were on stable targeted PAH therapy, received a single infusion of ≤1000mg ferric carboxymaltose. All patients were assessed at baseline and two months after iron treatment. Exercise capacity was evaluated based on the 6-minute-walking distance (6MWD), and quality of life (QoL) was assessed by the SF-36 questionnaire (100 point scale). The effects were compared to 20 matched patients with stable PAH without iron deficiency who did not receive ferric carboxymaltose. Results In iron deficient patients, iron supplementation led to a marked improvement of iron status (serum iron 5.7±0.4 to 11.1±1.1μmol/L, ferritin 29.3±6.3 to 145.2±25.4μg/L, transferrin saturation 7.5±0.7 to 19.3±2.3%, all p≤0.001). Iron-deficient patients receiving ferric carboxymaltose showed a significant increase of the 6MWD from 346.5±28.3 to 374.0±25.5m (p=0.007), whereas no significant changes were found in the control group not receiving iron supplementation (6MWD 389.9±25.3 to 379.6±26.2m; n.s.), resulting in a net increase in the 6MWD of 37.8m (p=0.003). This was associated with an improvement in QoL (SF-36 score from 44.3±3.7 to 50.6±3.6; p=0.01). Only minimal side-effects were reported. Conclusions These data indicate that parenteral iron supplementation with ferric carboxymaltose significantly improves exercise capacity and QoL and is well tolerated in patients with PAH and iron deficiency, and when administered in addition to targeted PAH therapies. Our results provide proof of concept for further studies evaluating the potential of iron as an adjunct in PAH treatment on a larger scale. [ABSTRACT FROM AUTHOR]

Aims CD73 (ecto-5′-nucleotidase) is expressed by a broad range of immune cells and attenuates inflammation in several acute disease models. This study therefore explored the role of CD73-derived adenosine in a model of chronic vascular inflammation such as atherogenesis. Methods and results CD73−/− mice were backcrossed into the apolipoprotein E (ApoE−/−) background. In CD73−/−/ApoE−/− double mutants, atherosclerotic lesion formation was increased by ∼50% compared with ApoE−/−. However, the cellular composition and extracellular matrix of the plaques did not differ. Surprisingly, we found significant activity and expression of CD73 in the plaque of ApoE−/− mice which increased over time. CD73 co-localized with macrophages, Tregs, and cells of mesenchymal origin. Genome-wide microarray analysis of the aorta lacking CD73 revealed upregulation of endothelin-1 (Edn1) mRNA together with changes of genes in lipid metabolism and the Wnt and nuclear factor kappa B pathways. Measurement of plasma levels verified the upregulation of Edn1 in CD73−/− and double mutants. Plasma triglycerides (TG) were also found to be significantly elevated in the CD73−/−/ApoE−/− mice compared with ApoE−/− controls. Conclusion Lack of CD73 promotes atherogenesis most likely by de-inhibition of resident macrophages and T cells. Elevated Edn1 and TG levels may have contributed. This establishes CD73-derived adenosine as a direct or indirect regulator of atherogenesis. [ABSTRACT FROM PUBLISHER]

Abstract: The transplantation of pigment epithelial cells as a therapeutic modality for retinal degeneration requires that the transplanted cells form a monolayer in the subretinal space that will establish communication with photoreceptors. Since previous studies have shown that transplanted cells in suspension do not form a monolayer, it will be necessary to transplant preformed pigment epithelial cell monolayers at the location of the exposed photoreceptors. To establish cell monolayers, retinal pigment epithelial (RPE) cells were cultured on ultrathin collagen membranes. Cells were examined for morphology, for characteristics of differentiation and viability. Membrane degradation and long-term biocompatibility in vivo were assessed following subconjunctival and subretinal implantation in rabbits. These studies have shown that RPE cells adhere, proliferate, form monolayers, and acquire differentiated properties on a collagen membrane that has features similar to Bruch''s membrane. Membranes transplanted subconjunctivally and subretinally exhibit excellent biocompatibility without any evidence of inflammation or rejection. RPE cells cultured on collagen membranes acquire differentiated characteristics similar to those of RPE cells in vivo and form complete monolayers that are amenable to be transplanted to the subretinal space. The collagen membranes are non-toxic and do not elicit any rejection or inflammatory response when implanted subconjunctivally or subretinally in rabbits. [Copyright &y& Elsevier]

In the article, the authors present a systematic study on the cases of silent hypoxemia in COVID-19 patients and their implications for outpatient care. Topics include the Medical Emergency Team (MET) pilot project by the Municipal Fire Brigade Cologne to conduct medical interventions in said patients and the associated risk of peracute respiratory decompensation and dynamic deterioration in silent hypoxemia.