OBJECTIVES The purpose of this study was to assess the functional and prognostic correlates of B-lines during stress echocardiography (SE). BACKGROUND B-profile detected by lung ultrasound (LUS) is a sign of pulmonary congestion during SE. METHODS The authors prospectively performed transthoracic echocardiography (TTE) and LUS in 2,145 patients referred for exercise (n = 1,012), vasodilator (n = 1,054), or dobutamine (n = 79) SE in 11 certified centers. B-lines were evaluated in a 4-site simplified scan (each site scored from 0: A-lines to 10: white lung for coalescing B-lines). During stress the following were also analyzed: stress-induced new regional wall motion abnormalities in 2 contiguous segments; reduced left ventricular contractile reserve (peak/rest based on force, ≤2.0 for exercise and dobutamine, ≤1.1 for vasodilators); and abnormal coronary flow velocity reserve ≤2.0, assessed by pulsed-wave Doppler sampling in left anterior descending coronary artery and abnormal heart rate reserve (peak/rest heart rate) ≤1.80 for exercise and dobutamine (≤1.22 for vasodilators). All patients completed follow-up. RESULTS According to B-lines at peak stress patients were divided into 4 different groups: group I, absence of stress B-lines (score: 0 to 1; n = 1,389; 64.7%); group II, mild B-lines (score: 2 to 4; n = 428; 20%); group III, moderate B-lines (score: 5 to 9; n = 209; 9.7%) and group IV, severe B-lines (score: ≥10; n = 119; 5.4%). During median follow-up of 15.2 months (interquartile range: 12 to 20 months) there were 38 deaths and 28 nonfatal myocardial infarctions in 64 patients. At multivariable analysis, severe stress B-lines (hazard ratio [HR]: 3.544; 95% confidence interval [CI]: 1.466 to 8.687; p = 0.006), abnormal heart rate reserve (HR: 2.276; 95% CI: 1.215 to 4.262; p = 0.010), abnormal coronary flow velocity reserve (HR: 2.178; 95% CI: 1.059 to 4.479; p = 0.034), and age (HR: 1.031; 95% CI: 1.002 to 1.062; p = 0.037) were independent predictors of death and nonfatal myocardial infarction. CONCLUSIONS Severe stress B-lines predict death and nonfatal myocardial infarction. (Stress Echo 2020 - The International Stress Echo Study [SE2020]; NCT03049995).

Trans-resveratrol becomes more and more popular all over the world as a powerful antioxidant. Since its positive properties, including antioxidant, anti-inflammatory, anti-tumor are indisputable, nowadays trans-resveratrol is used as a component of various products from nutriceutics to body care formulations, where it is supposed to behave as natural antioxidant and anti-aging compound. It is also added to food packaging materials to increase their stability or/and prevent oxidation. Nevertheless, being released to the environment resveratrol easily forms various transformation products with potentially negative environmental and health effects. The present paper deals with transformation of pure resveratrol and its formulation used as UV-protectors in conditions of aquatic chlorination. Over 80 transformation products were tentatively identified using gas chromatography-high resolution mass spectrometry (GC-HRMS) and ultra pressure liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). Chlorinated phenols and biphenyls are the most relevant among them. Estimation of toxicity of resveratrol products was carried out using luminescent bacteria V. fischeri tests.

Estimation of unmeasured variables is a crucial objective in a broad range of applications. However, the estimation process turns into a challenging problem when the underlying model is nonlinear and even more so when additionally it exhibits multiple time scales. The existing results on estimation for systems with two time scales apply to a limited class of nonlinear plants and observers. We focus on analyzing nonlinear observers designed for the slow state variables of nonlinear singularly perturbed systems. Moreover, we consider the presence of bounded measurement noise in the system. We generalize current results by considering broader classes of plants and estimators to cover reduced‐order, full‐order, and higher‐order observers. First, we show that the singularly perturbed system has bounded solutions under an appropriate set of assumptions on the corresponding boundary layer and reduced systems. We then exploit this property to prove that, under reasonable assumptions, the error dynamics of the observer designed for the reduced system are semiglobally input‐to‐state practically stable when the observer is implemented on the original plant. We also conclude ℒ2 stability results when the measurement noise belongs to ℒ2∩ℒ∞ . In the absence of measurement noise, we state results on semiglobal practical asymptotical stability for the error dynamics. We illustrate the generality of our main results through three classes of systems with corresponding observers and one numerical example.

Flour-based confectionary is the most popular confectionary and have an important position in food technology in general. Those products present the most often consumed confectionary products and their growth in EU market has been increasing per capita consumption [1] owing to their sweet taste and nice aroma and flavor, easy accessibility–ready to use and well-established habits [2], lower production costs, convenience and long shelf life [3].

In medium-size, spiny striatal neurons of the direct pathway, dopamine D1- and adenosine A1-receptors are co-expressed and are mutually antagonistic. Recently, a mutation in the gene encoding the A1-receptor (A1R-G279S7.44) was identified in an Iranian family: two affected off-springs suffered from early onset L-DOPA-responsive Parkinson's disease. The link between the mutation and the phenotype is unclear. Here, we explored the functional consequence of the G279S substitution on the activity of the A1-receptor after heterologous expression in HEK293 cells. The mutation did not affect surface expression and ligand binding, but changed the susceptibility to heat denaturation: the thermodynamic stability of A1R-G279S7.44was enhanced by about 2 and 8 K when compared to wildtype A1-receptorand A1R-Y288A7.53 (a folding-deficient variant used as a reference), respectively. In contrast, the kinetic stability was reduced indicating a lower energy barrier for conformational transitions in A1R-G279S7.44(73 {plus minus} 23 kJ/mol) than in wildtype A1R(135 {plus minus} 4 kJ/mol) or in A1R-Y288A7.53 (184 {plus minus} 24 kJ/mol). Consistent with this lower energy barrier, A1R-G279S7.44was more effective in promoting guanine nucleotide-exchange than wildtype A1R. We detected similar levels of complexes formed between D1-receptors and wildtype A1R or A1R-G279S7.44by co-immunoprecipitation and bioluminescence resonance energy transfer (BRET). However, lower concentrations of agonist were required for half-maximum inhibition of dopamine-induced cAMP accumulation in cells co-expressing D1-receptor and A1R-G279S7.44than in those co-expressing wildtype A1R. These observations predict enhanced inhibition of dopa-minergic signaling by A1R-G279S7.44 in vivo consistent with a pathogenic role in Parkinson's disease. Significance Statement Parkinson's diseaseis caused by a loss of dopaminergic input from the substantia nigrato the caudate nucleus and the putamen. Activation of the adenosine A1-receptor antagonizes respon-ses elicited by dopamine D1-receptors. We show that this activity is more pronounced in a mutant version of the adenosine A1-receptor (A1R-G279S7.44), which was identified in individuals suffering from early onset Parkinson's disease.

The aim of this paper is to present and validate a framework for assessing healthcare facilities in low-resource settings to collect evidence and inform policies on the harmonisation, regulation and contextualised design of medical devices. A literature review and focus groups with several experts of medical device design, clinical engineering, health technology assessment and management, allowed the creation of a protocol, comprising two parts: a semi-structured interview and electrical safety measures. Three hospitals were assessed in Benin and three in Uganda. All the health centres resulted to be facing typical challenges for low-resource settings, including the lack of funding, expertise, a well-established maintenance program, spare parts and consumables, and unreliable power supplies. As there is a paucity of information regarding low-resource settings, the proposed framework can be used by clinical or biomedical engineers to assess and thereby propose actions for improving the conditions of healthcare settings.

Purpose The aim of this paper is to present and validate a framework for assessing healthcare facilities in low-resource settings to collect evidence and inform policies on the harmonisation, regulation and contextualised design of medical devices. Methods A literature review and focus groups with several experts of medical device design, clinical engineering, health technology assessment and management, allowed the creation of a protocol, comprising two parts: a semi-structured interview and electrical safety measures. Results Three hospitals were assessed in Benin and three in Uganda. All the health centres resulted to be facing typical challenges for low-resource settings, including the lack of funding, expertise, a well-established maintenance program, spare parts and consumables, and unreliable power supplies. Conclusion As there is a paucity of information regarding low-resource settings, the proposed framework can be used by clinical or biomedical engineers to assess and thereby propose actions for improving the conditions of healthcare settings.

Apesar de decorrer das praticas sociais vivenciadas pelos universitarios, o ensino da escrita academica tem sido pouco presente nos cursos de licenciaturas. Isso se reflete na formacao desses estudantes e futuros professores, que costumam apresentar lacunas no ler-escrever textos da esfera academica. Considerada ainda a escassez de producoes cientificas brasileiras acerca desse tema, este estudo busca investigar as principais tendencias da producao cientifica sobre letramento academico na formacao de professores na area de Letras, publicadas no banco de teses da CAPES, entre 2013 e 2017, visando mapear os desafios e as contribuicoes do debate acerca do letramento academico na formacao de professores. Trata-se de uma pesquisa bibliografica do tipo estado da arte que considera os trabalhos completos de dissertacoes e teses publicadas nessa plataforma e desenvolvidas no contexto brasileiro. Nessa investigacao, encontraram-se apenas quatro trabalhos publicados sobre o tema na area de Letras, reafirmando a necessidade de investimento em pesquisa para avancar nas imbricacoes entre letramentos academicos e letramento docente.

Abstract. In this paper we evaluate characteristics of three optical particulate matter sensors/sizers (OPS): high-end spectrometer 11-D (Grimm, Germany), low-cost sensor OPC-N2 (Alphasense, United Kingdom) and in-house developed MAQS (Mobile Air Quality System), which is based on another low-cost sensor – PMS5003 (Plantower, China), under realistic conditions of strong and mild urban pollution. Results were compared against a reference gravimetric system, based on a Gemini (Dadolab, Italy), 2.3 m3 h−1 air sampler, with two channels (simultaneously measuring PM2.5 and PM10 concentrations). The measurements were performed in Sarajevo, the capital of Bosnia-Herzegovina, from December 2019 until May 2020. This interval is divided into period 1 – strong pollution – and period 2 – mild pollution. The city of Sarajevo is one of the most polluted cities in Europe in terms of particulate matter: the average concentration of PM2.5 during the period 1 was 83 µg m−3, with daily average values exceeding 500 µg m−3. During period 2, the average concentration of PM2.5 was 20 µg m−3. These conditions represent a good opportunity to test optical devices against the reference instrument in a wide range of ambient particulate matter (PM) concentrations. The effect of an in-house developed diffusion dryer for 11-D is discussed as well. In order to analyse the mass distribution of particles, a scanning mobility particle sizer (SMPS), which together with the 11-D spectrometer gives the full spectrum from nanoparticles of diameter 10 nm to coarse particles of diameter 35 µm, was used. All tested devices showed excellent correlation with the reference instrument in period 1, with R2 values between 0.90 and 0.99 for daily average PM concentrations. However, in period 2, where the range of concentrations was much narrower, R2 values decreased significantly, to values from 0.28 to 0.92. We have also included results of a 13.5-month long-term comparison of our MAQS sensor with a nearby beta attenuation monitor (BAM) 1020 (Met One Instruments, USA) operated by the United States Environmental Protection Agency (US EPA), which showed similar correlation and no observable change in performance over time.

Nanosheet heterostructures offer emergent optical/electronic properties. These could be achieved using selective materials binding peptides, but lack of understanding of selectivity impedes advancement. Here we examine peptides with affinity for graphene or h-BN using quantitative experiments and molecular simulation to identify traits for design of 2D nanosheet selective peptides.

Von Willebrand factor (VWF) plays a major role in arterial thrombosis. Antiplatelet drugs induce only a moderate relative risk reduction after atherothrombosis, and their inhibitory effects are compromised under high shear rates when VWF levels are increased. Therefore, we investigated the ex vivo effects of a third-generation anti-VWF aptamer (BT200) before/after stimulated VWF release. We studied the concentration-effect curves BT200 had on VWF activity, platelet plug formation under high shear rates (PFA), and ristocetin-induced platelet aggregation (Multiplate) before and after desmopressin or endotoxin infusions in healthy volunteers. VWF levels increased > 2.5-fold after desmopressin or endotoxin infusion (p < 0.001) and both agents elevated circulating VWF activity. At baseline, 0.51 µg/ml BT200 reduced VWF activity to 20% of normal, but 2.5-fold higher BT200 levels were required after desmopressin administration (p < 0.001). Similarly, twofold higher BT200 concentrations were needed after endotoxin infusion compared to baseline (p < 0.011). BT200 levels of 0.49 µg/ml prolonged collagen-ADP closure times to > 300 s at baseline, whereas 1.35 µg/ml BT200 were needed 2 h after desmopressin infusion. Similarly, twofold higher BT200 concentrations were necessary to inhibit ristocetin induced aggregation after desmopressin infusion compared to baseline (p < 0.001). Both stimuli elevated plasma VWF levels in a manner representative of thrombotic or pro-inflammatory conditions such as arterial thrombosis. Even under these conditions, BT200 potently inhibited VWF activity and VWF-dependent platelet function, but higher BT200 concentrations were required for comparable effects relative to the unstimulated state.