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Background: Positive bronchodilator reversibility (BDR) is a diagnostic criterion for asthma. However, patients with asthma may exhibit negative BDR test. Aim: To describe frequency of positive and negative BDR in patients with severe asthma and associations with phenotypic characteristics. Methods: Positive BDR was defined as FEV1 increase > 200 ml AND > 12% upon testing with a short-acting beta-agonist (SABA). Results: Out of 2013 patients included in the German Asthma Net (GAN) severe asthma registry, 793 had data on BDR. Hereof, 250 (31.5%) had a positive and 543 (68.5%) had a negative BDR test. Comorbidities significantly associated with negative BDR were gastro-esophageal reflux (GERD) (28.0% vs 40.0%, p

Background Air trapping and lung hyperinflation are major determinants of prognosis and response to therapy in chronic obstructive pulmonary disease (COPD). They are often determined by body plethysmography, which has limited availability, and so the question arises as to what extent they can be estimated via spirometry. Methods We used data from visits 1–5 of the COPD cohort COSYCONET. Predictive parameters were derived from visit 1 data, while visit 2–5 data was used to assess reproducibility. Pooled data then yielded prediction models including sex, age, height, and body mass index as covariates. Hyperinflation was defined as ratio of residual volume (RV) to total lung capacity (TLC) above the upper limit of normal. (ClinicalTrials.gov identifier: NCT01245933). Results Visit 1 data from 1988 patients (Global Initiative for Chronic Obstructive Lung Disease grades 1–4, n=187, 847, 766, 188, respectively) were available for analysis (n=1231 males, 757 females; mean±sd age 65.1±8.4 years; forced expiratory volume in 1 s (FEV1) 53.1±18.4 % predicted (% pred); forced vital capacity (FVC) 78.8±18.8 % pred; RV/TLC 0.547±0.107). In total, 7157 datasets were analysed. Among measures of hyperinflation, RV/TLC showed the closest relationship to FEV1 % pred and FVC % pred, which were sufficient for prediction. Their relationship to RV/TLC could be depicted in nomograms. Even when neglecting covariates, hyperinflation was predicted by FEV1 % pred, FVC % pred or their combination with an area under the curve of 0.870, 0.864 and 0.889, respectively. Conclusions The degree of air trapping/hyperinflation in terms of RV/TLC can be estimated in a simple manner from forced spirometry, with an accuracy sufficient for inferring the presence of hyperinflation. This may be useful for clinical settings, where body plethysmography is not available., This proposed method allows estimation of hyperinflation in COPD by spirometry, obviating the need for body plethysmography or further techniques. Results are depicted in easily applicable nomograms that can be used in clinical practice. https://bit.ly/3c0tUNL

In the EU, five biologics have been approved as add-on therapy for patients with severe asthma. Until recently, none of the biologics was approved for home use and had to be administered under medical supervision, a time-consuming schedule for both patients and physicians, accompanied by greater expenditure. However, over the last year, four out of the five biologics have been granted approval for patient self-administration at home. The objective of this multiple-choice survey was to understand how patients with severe asthma treated with omalizumab and their treating physicians view the potential home use of biologics exemplified by omalizumab. The questionnaires were answered by 120 physicians and 432 patients (response rate: 51.7 % and 20.6 %, respectively). Overall, 44.7 % of patients were in favour of self-administration at home while 30.6 % opposed this method of administration and 23.8 % of patients were neutral. Especially teenagers and young adults had a positive attitude towards self-administration. 76.7 % of the questioned physicians were in favour of home use for certain patients. Time saving was the main advantage for self-administration mentioned by patients (53.2 %) as well as by physicians (72.5 %). The main concern for patients was 'making a mistake while injecting' (43.8 %) while 'forgetting to inject omalizumab' (73.3 %) was the main concern for physicians. 44.4 % of patients expressed a wish for individual training and 70.8 % of physicians agreed with this statement. The latter group also considered a starter kit including several information materials (54.2 %) as well as an electronic reminder system (50.8 %) as useful. In conclusion, self-administration of biologics has the potential to be timesaving for both patients and physicians.In der EU sind derzeit 5 Biologika als Add-on-Behandlung bei schwerem Asthma zugelassen. Bisher musste die Administration unter medizinischer Aufsicht erfolgen, was sowohl für Patienten als auch Arztpraxen mit einem erhöhten Zeit- und Kostenaufwand einhergeht. Im Laufe des letzten Jahres wurde allerdings die Selbstapplikation für 4 der 5 Biologika zugelassen. Ziel dieser Umfrage war es, mittels Multiple-Choice-Fragebögen das Potenzial einer Selbstapplikation von Biologika aus der Sicht von Patienten und Ärzten am Beispiel von Omalizumab einzuschätzen. In die Auswertung flossen 432 Patienten- und 120 Ärzte-Fragebögen ein (Rücklaufquote: 51,7 % bzw. 20,6 %). Insgesamt bewerteten 44,7 % der Patienten eine Selbstapplikation positiv, 30,6 % ablehnend und 23,8 % neutral. V. a. in den Altersgruppen der Jugendlichen und jungen Erwachsenen wurde eine Selbstapplikation überwiegend positiv bewertet. 76,7 % der befragten Ärzte würden eine Selbstapplikation für bestimmte Patienten befürworten. Als wichtigster Vorteil wurde bei Patienten bzw. Ärzten v. a. die Zeitersparnis (53,2 % bzw. 72,5 %) genannt. Bedenken äußerten die Patienten v. a. zu Fehlern beim Spritzen (43,8 %), während bei Ärzten am häufigsten „vergessen Omalizumab zu spritzen“ (73,3 %) genannt wurde. Von 44,4 % der Patienten wurde der Wunsch nach einer persönlichen Schulung zur Selbstapplikation als Unterstützung geäußert, während bei den Ärzten neben dieser Unterstützung (70,8 %) v. a. auch ein Starterkit mit verschiedensten Infomaterialien (54,2 %) sowie ein elektronisches Erinnerungs-System (App) als sinnvoll erachtet wurden (50,8 %). Zusammenfassend ergab die Umfrage, dass die praxisexterne Selbstapplikation von Biologika sowohl bei Patienten als auch Ärzten überwiegend befürwortet wurde und zu einer Zeitersparnis beitragen kann.

Systemic allergic reactions to vaccines are very rare. In this study we assessed the management and outcome suspected SARS-CoV-2 vaccine hypersensitivity. We present data of 219 individuals, who experienced symptoms suspicious for an allergic reaction after the first (n=214) or the second vaccination (n=5). 195 reactions occurred after the first application of mRNA-based vaccines (157 Comirnaty®, and 38 Spikevax®) and eighteen reactions were reported after first application of a vector vaccine (Vaxzevria®). Of these 162 experienced immediate symptoms. Skin symptoms occurred in 91 cases. The most frequent cutaneous symptom was angioedema (n=45), followed by generalized urticaria (n=36) and generalized erythema/flush (n=20). 70 patients had cardiovascular symptoms, 45 showed respiratory symptoms and gastrointestinal symptoms were recorded in 14 patients. The allergological assessment of 334 individuals (219 with reactions after COVID vaccination and 115 with a history of vaccine related reactions) showed in 17% a suspicion of sensitization against the SARS-CoV-2 vaccine and/or their ingredients defined as one positive skin test and/or BAT. The majority of the SPT/IDT with the vaccines were negative. Of the 214 patients with suspected allergic symptoms after the first vaccination, 67/67 patients tolerated the re-vaccination. In this study, 334 individuals of a cohort resembling >2000 persons presenting for an allergy workup regarding SARS-CoV-2 vaccination only 45 were diagnosed in concordance with the anaphylaxis definition of the Brighton collaboration with anaphylactic immediate hypersensitivity reaction after SARS-CoV-2 vaccination. Identifiable characteristics of these patients with suspected, but also diagnosed SARS-CoV-2 vaccine hypersensitivity were female gender and the symptom angioedema. Overall, IgE-mediated hypersensitivity towards SARS-CoV-2 vaccines is extremely low and not increased in comparison to the reported hypersensitivity for other vaccines.

Background Peripheral neuropathy is a common comorbidity in COPD. We aimed to investigate associations between alterations commonly found in COPD and peripheral neuropathy, with particular emphasize on the distinction between direct and indirect effects. Methods We used visit 4 data of the COPD cohort COSYCONET, which included indicators of polyneuropathy (repeated tuning fork and monofilament testing), excluding patients with diabetes a/o increased HbA1c. These indicators were analysed for the association with COPD characteristics, including lung function, blood gases, 6-min walk distance (6-MWD), timed-up-and-go-test (TUG), exacerbation risk according to GOLD, C-reactive protein (CRP), and ankle-brachial index (ABI). Based on the results of conventional regression analyses adjusted for age, BMI, packyears and gender, we utilized structural equation modelling (SEM) to quantify the network of direct and indirect relationships between parameters. Results 606 patients were eligible for analysis. The indices of polyneuropathy were highly correlated with each other and related to base excess (BE), ABI and TUG. ABI was linked to neuropathy and 6-MWD, exacerbations depended on FEV1, 6-MWD and CRP. The associations could be summarized into a SEM comprising polyneuropathy as a latent variable (PNP) with three measured indicator variables. Importantly, PNP was directly dependent on ABI and particularly on BE. When also including patients with diabetes and/or elevated values of HbA1c (n = 742) the SEM remained virtually the same. Conclusion We identified BE and ABI as major determinants of peripheral neuropathy in patients with COPD. All other associations, particularly those with lung function and physical capacity, were indirect. These findings underline the importance of alterations of the micromilieu in COPD, in particular the degree of metabolic compensation and vascular status.

Anodes manufactured from NiO- and yttria-stabilized zirconia (Y2O3 doped ZrO2, YSZ) powders are today's state of the art for solid oxide fuel cells (SOFCs) because they are easy to manufacture and have high performance in both anode-supported and electrolyte-supported cells. However, such cells can show significant degradation or fail completely if nickel is reoxidized during high-temperature operation even though it can be reduced again. Tests with stacks and systems have shown that system shutdown procedures, accidental air entry due to component failure or controlled air feed to the anode side as a result of operational necessities may occur and result in the reoxidation of the metallic nickel. This reoxidation is not only associated with a volume expansion, but also with significant structural changes in the anode microstructure, generating stresses in the anode itself, as well as in the electrolyte. These stresses can exceed the stability of the components, potentially promoting crack growth, which leads to degradation of the SOFC or complete failure. This problem has been addressed by a number of contributions in the literature over the last decade, but interest is increasing, particularly because SOFC systems are being discussed for transport and mobile applications requiring new system specifications. The most critical problem to be overcome is the tolerance of a large number of intentional redox cycles due to system requirements during operating lifetime. This article gives an overview of the various approaches to the redox problem by summarizing many of the contributions, starting with a basic understanding of the underlying physicochemical processes of Ni reduction and oxidation and ending at stack-level results, leading finally to their combination with recent findings. It aims to elaborate reliable results and open questions on this topic considering the mechanical and electrochemical aspects of the problem.

The internal reforming of methane in a solid oxide fuel cell (SOFC) is investigated and modeled for flow conditions relevant to operation. To this end, measurements are performed on anode-supported cells (ASC), thereby varying gas composition (yCO = 4–15%, y H 2 = 5 − 17 % , y C O 2 = 6 − 18 % , y H 2 O = 2 − 30 % , y C H 4 = 0.1 − 20 % ) and temperature (600–850 °C). In this way, operating conditions for both stationary applications (methane-rich pre-reformate) as well as for auxiliary power unit (APU) applications (diesel-POX reformate) are represented. The reforming reaction is monitored in five different positions alongside the anodic gas channel by means of gas chromatography. It is shown that methane is converted in the flow field for methane-rich gas compositions, whereas under operation with diesel reformate the direction of the reaction is reversed for temperatures below 675 °C, i.e. (exothermic) methanation occurs along the anode. Using a reaction model, a rate equation for reforming could be derived which is also valid in the case of methanation. By introducing this equation into the reaction model the methane conversion along a catalytically active Ni-YSZ cermet SOFC anode can be simulated for the operating conditions specified above.

The influence of hydrocarbons containing fuel gases on cell performance and coke formation is investigated in this work, wherein acetylene is applied as model compound for the coke formation. The dependence of coke yield on acetylene amount (volume fraction of 0.05% to 0.50%) and gas composition is analyzed. Further parameters, which are varied, are temperature (650 {degree sign}C to 850 {degree sign}C) and operation time. It could be shown, that the mass of coke, that is formed on the cell, depends strongly on acetylene volume fraction and temperature. As a consequence acetylene has a severe influence on the electrical cell performance and acetylene concentration and temperature can be correlated to degradation effects.

The internal reforming of methane on Ni/CGO and Ni/YSZ anodes was investigated with single cells operated at steam to carbon ratios from 0 to 3 and at temperatures of 800 °C and 950 °C. The incorporation of gas extraction ports allowed the measurement of the local gas composition in the anode gas compartment by gas chromatography. The methane conversion is presented as a function of feed gas composition, temperature, gas flow velocity, and electrical load. The impact of the anode material on the reforming reaction and on cell performance is shown. Methane conversion along the Ni/CGO anode was calculated with a one-dimensional model; the required kinetic parameters were obtained by data fitting.

This study presents new geochemical (major and trace element, Nd–Sr isotope) and U–Pb zircon, monazite, titanite and rutile data for various rock types (eclogite, high-pressure granulite, amphibolite, orthogneiss, leucosome) of the high-grade metamorphic Marianske Lazně Complex in the western Bohemian Massif. Concordant U–Pb zircon analyses from the mafic to intermediate samples disclose the Marianske Lazně Complex as a mixture of c. 540 Ma oceanic rocks juxtaposed at depth with lower-crustal rocks of the structurally overlying Tepla–Barrandian Unit. This interpretation refutes earlier models in which the Marianske Lazně Complex was interpreted as a dismembered Cambro-Ordovician ophiolite complex affected by Variscan subduction. Metamorphic zircon in mafic rocks of the Marianske Lazně Complex, as well as monazite from orthogneiss, and titanite in leucosome yield ages around 380 Ma. On the basis of detailed petrography and cathodoluminescence imaging we conclude that the c. 380 Ma age reflects the timing of Variscan exhumation and associated decompression melting under upper amphibolite-facies to granulite-facies conditions. Thereby, the data derived from metamorphic zircon of eclogites and high-pressure granulite, unexpectedly, do not date the timing of eclogitization, which could have happened just before Variscan exhumation, or even shortly after Late Cadomian protolith formation.

New U–Pb monazite and zircon data combined with a study of their internal morphologies significantly clarifies the controversy surrounding the Palaeozoic geodynamic evolution of the Sudetes Mountains in the northeastern Bohemian Massif. Variably thin rims of secondary magmatic overgrowth on zircons from an anatectic granite in the Góry Sowie block are dated by a U–Pb zircon lower intercept age of 353±61 Ma, by magmatic monazite growth at 378±2 Ma, and by xenotime crystallization at 383–370 Ma in a late syntectonic pegmatite, reflecting the anatectic event associated with a single‐cycle Variscan orogeny in this area.

New U–Pb zircon and titanite data from the Muskoka domain, Grenville Province, Ontario, provide protolith and metamorphic ages for the southwestern Central Gneiss Belt. Discordant analyses from a migmatitic orthogneiss and its leucosome form a linear array with an upper intercept age of 1457 ± 6 Ma and a lower intercept age of 1064 ±18 Ma. U–Pb analyses on metamorphic zircon from an amphibolite yield a set of concordant analyses with an average 207Pb/206Pb age of 1079 ± 3 Ma. A weakly migmatitic granitoid rock and a transecting charnockitic vein in the immediate footwall of the Central Metasedimentary Belt boundary thrust zone yielded a discordant array of analyses wth an upper intercept age of 1394 ± 13 Ma and a lower intercept age of 1066 ± 8 Ma. The charnockitic vein yielded concordant zircon ages of 1077 ± 2 Ma. The upper intercept ages are interpreted in terms of protolith crystallization, and the concordant and lower intercept ages as Grenviilian high-grade metamorphism and associated anatexis. We have found no evidence for a ca. 1190–1160 Ma metamorphic event in these rocks, as required by some regional tectonic interpretations. We conclude that emplacement of the Central Metasedimentary Belt over the Central Gneiss Belt, which caused high-grade metamorphism in the Muskoka domain, occurred at or shortly before ca. 1080 Ma, and that this marks the time of accretion of the Central Metasedimentary Belt to the southeast margin of Laurentia.

Anodes for stationary SOFC systems are most likely to be operated with natural gas at temperatures above 800 °C, whereas mobile SOFC applications such as APUs (auxiliary power units) operated below 800 °C use (liquid) hydrocarbons. The fuel (gasoline or diesel) cannot be converted by 100% in the reformer and so a reformate containing higher hydrocarbons has to be converted at the anode. In operation with hydrocarbons, at high fuel utilization or at sequential redox cycles, the nickel catalyst is subject to various degradation processes. The dominating process depends on the anodic oxygen partial pressure applied and possibly deteriorates the electrochemical performance of the anode. Sequential cyclic reduction and oxidation (redox) can quickly lead to an aging of the anode or even a complete failure of the cell (fracture of the thin film electrolyte). In operation with hydrocarbons, i.e., at low oxygen partial pressures, degradation ranging from (i) reversible damage by occupancy of the Ni catalyst surface with various deposits to (ii) irreversible damage to the Ni catalyst by carbon whisker growth occurs. Moreover, the kinetics of methane conversion under various operating conditions, the carbon formation in the presence of higher hydrocarbons (acetylene), and the analysis of electro-oxidation and gas diffusion in stable operation with hydrogen or biomass-derived gas are also treated in this article. Keywords: Ni/8 YSZ anode; methane reforming kinetics; redox durability; hydrocarbons; carbon deposition; biogas; impedance analysis; distribution of relaxation times

© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Chem. Ing. Tech. 2014, 86, No. 9, 1615–1632 Dye-ligand affinity chromatography is widely utilized for protein separation and purification. Immobilized textile trazine dyes, particularly Cibacron blue, have been applied as affinity chromatography tools for a long time. However, its interaction with a large number of seemingly unrelated proteins inevitably compromises its protein-binding specificity. This endows Cibacron blue with a serious drawback. To cope with the lack of specificity of textile dyes, a better understanding of the binding and specific mechanisms between dye-ligand and different proteins is required. For a detailed investigation into the interaction between Cibacron blue and proteins, molecular dynamics simulations were applied to study the interactions of Cibacron blue with two different proteins, serum albumin and hemoglobin. Allatom models of these affinity interaction systems were employed for a precise study. The interaction as well as the binding sites of proteins are analyzed and discussed in detail. For a better understanding of the specific mechanism, the simulations of these two proteins are compared. The simulation results are combined with the former experimental results to obtain a comprehensive understanding, which is important for the design of new dye-ligands as well as for optimization of dye-ligand affinity chromatography.

The internal reforming of methane in a solid oxide fuel cell (SOFC) has been modeled for operation conditions relevant to both stationary and auxiliary power unit (APU) applications. A 2D-FEM model was developed in COMSOL Multiphysics. Aim of this model is the space-resolved prediction of the gas composition in the anode side of planar anode supported single cells. The isothermal model accounts for the mass transport phenomena in the fuel-gas channel and the anode substrate. A global rate expression is applied to model the gas conversion caused by the internal reforming reactions. The kinetic parameters were fitted to experimental data. In the investigated parameter range, the model shows good correlation with experimental data. As the model is capable to coherently calculate the complex species transport phenomena and the kinetics of the chemical reactions, the limitation of pore transport on the effective chemical reaction kinetics can be reproduced with the model.

The influence of hydrocarbon-containing fuel gases on cell performance and coke formation is investigated in this work, wherein acetylene is applied as a model compound for the coke formation. The dependence of coke yield on acetylene amount (volume fraction of 0.05-0.50%) and gas composition is analyzed. Further parameters which are varied are temperature (650-850°C) and operation time. It is shown that the mass of coke that is formed on the cell depends strongly on acetylene volume fraction and temperature. As a consequence, acetylene has a severe influence on the electrical cell performance, and acetylene concentration and temperature can be correlated to degradation effects.

The aim of this study was to define the structural characteristics in a series of 21 analogues of the anti-histaminergic drug diphenhydramine which are important for the interaction with cytochrome P-450. The compounds gave substrate (type I) binding spectra with rat hepatic microsomal cytochrome P-450. The main findings were: (1) two phenyl rings are needed for strong binding: saturation or elimination of one ring, or restriction of two phenyls with a two-carbon bridge results in a decrease of binding, (2) substitution on one or both aromatic rings has only a small influence on binding, (3) an amine nitrogen contributes to better binding; decrease or absence of basicity weakens binding, and (4) a chain of 4 to 7 atoms connecting the basic centre with the aromatic part is needed; reduction of the chain length, or restriction of it to a cyclic structure causes decrease or loss of binding ability.

A one-dimensional model was developed which describes the conversion of methane on a planar Ni/CGO-anode. The model includes the reforming and the shift reactions. The simulation results were compared to gas concentrations measured at the inlet, the center and the outlet of the anode gas compartment by gas chromatography. The anode was operated at T = 800°C and T = 950°C, volumetric feed rates of v Φ N = 115 to 420 ml / min and steam-to-carbon ratios of 2 and 3, respectively. The results of the simulation agree well with the measured values.