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We studied whether in patients with COPD the use of metformin for diabetes treatment was linked to a pattern of lung function decline consistent with the hypothesis of anti-aging effects of metformin. Patients of GOLD grades 1–4 of the COSYCONET cohort with follow-up data of up to 4.5 y were included. The annual decline in lung function (FEV1, FVC) and CO diffusing capacity (KCO, TLCO) in %predicted at baseline was evaluated for associations with age, sex, BMI, pack-years, smoking status, baseline lung function, exacerbation risk, respiratory symptoms, cardiac disease, as well as metformin-containing therapy compared to patients without diabetes and metformin. Among 2741 patients, 1541 (mean age 64.4 y, 601 female) fulfilled the inclusion criteria. In the group with metformin treatment vs. non-diabetes the mean annual decline in KCO and TLCO was significantly lower (0.2 vs 2.3, 0.8 vs. 2.8%predicted, respectively; p 1 and FVC. These results were confirmed using multiple regression and propensity score analyses. Our findings demonstrate an association between the annual decline of lung diffusing capacity and the intake of metformin in patients with COPD consistent with the hypothesis of anti-aging effects of metformin as reflected in a surrogate marker of emphysema.

The aviation industry has committed itself to a scenario of reduction in emissions over the 3 decades ahead, which is especially challenging to fulfil as air traffic is expected to grow in the same time span. On the technical side, this calls for the development of radical aircraft technologies, such as the hybridization of the powertrain, or the use of different energy carriers (battery, hydrogen), which have been increasingly investigated in recent years. To this day however, it is not clear which technology combination could best address a given set of aircraft requirements, how realisable are such prospective aircraft designs within the time frame considered, nor how would those radical vehicle compare against conventional aircraft on the basis of techno-economic performance metrics. The CHYLA project at providing insights on those points, by providing an overview of scaling opportunities, challenges and limitations of key radical technologies where the credibility of underlying technology assumptions is an explicit factor in developing such a landscape. The presentation presents technical progress made in the project scope on three areas. First on energy network, where the behaviour of individual components of the network are modelled rather than assumed to provide a higher-fidelity design. Then on aircraft design, where a range of radical technology combinations, together with their underlying assumptions, can be tested on aircraft of various top-level requirements. Finally on the concept of “credible aircraft design” and its integration within an optimization framework, in order to find the best-performing vehicle that abides by a certain credibility level.

Alterations of cognitive functions have been described in COPD. Our study aimed to disentangle the relationship between the degree of cognitive function and COPD characteristics including quality of life (QoL).Data from 1969 COPD patients of the COSYCONET cohort (GOLD grades 1–4; 1216 male/ 753 female; mean (SD) age 64.9 ± 8.4 years) were analysed using regression and path analysis. The DemTect screening tool was used to measure cognitive function, and the St. George‘s respiratory questionnaire (SGRQ) to assess disease-specific QoL.DemTect scores were =60 years of age. For statistical reasons, we used the average of both algorithms independent of age in all subsequent analyses. The DemTect scores were associated with oxygen content, 6-min-walking distance (6-MWD), C-reactive protein (CRP), modified Medical Research Council dyspnoea scale (mMRC) and the SGRQ impact score. Conversely, the SGRQ impact score was independently associated with 6-MWD, FVC, mMRC and DemTect. These results were combined into a path analysis model to account for direct and indirect effects. The DemTect score had a small, but independent impact on QoL, irrespective of the inclusion of COPD-specific influencing factors or a diagnosis of cognitive impairment.We conclude that in patients with stable COPD lower oxygen content of blood as a measure of peripheral oxygen supply, lower exercise capacity in terms of 6-MWD, and higher CRP levels were associated with reduced cognitive capacity. Furthermore, a reduction in cognitive capacity was associated with reduced disease-specific quality of life. As a potential clinical implication of this work, we suggest to screen especially patients with low oxygen content and low 6-MWD for cognitive impairment.

We studied whether in patients with stable COPD blood gases (BG), especially oxygenated hemoglobin (OxyHem) as a novel biomarker confer information on disease burden and prognosis and how this adds to the information provided by the comorbidity pattern and systemic inflammation. Data from 2137 patients (GOLD grades 1–4) of the baseline dataset of the COSYCONET COPD cohort were used. The associations with dyspnea, exacerbation history, BODE-Index (cut-off ≤2) and all-cause mortality over 3 years of follow-up were determined by logistic and Cox regression analyses, with sex, age, BMI and pack years as covariates. Predictive values were evaluated by ROC curves. Capillary blood gases included SaO2, PaO2, PaCO2, pH, BE and the concentration of OxyHem [haemoglobin (Hb) x fractional SaO2, g/dL] as a simple-to-measure correlate of oxygen content. Inflammatory markers were WBC, CRP, IL-6 and -8, TNF-alpha and fibrinogen, and comorbidities comprised a broad panel including cardiac and metabolic disorders. Among BG, OxyHem was associated with dyspnoea, exacerbation history, BODE-Index and mortality. Among inflammatory markers and comorbidities, only WBC and heart failure were consistently related to all outcomes. ROC analyses indicated that OxyHem provided information of a magnitude comparable to that of WBC, with optimal cut-off values of 12.5 g/dL and 8000/µL, respectively. Regarding mortality, OxyHem also carried independent, additional information, showing a hazard ratio of 2.77 (95% CI: 1.85–4.15, p 8000/µL was 2.33 (95% CI: 1.60–3.39, p 2. It thus appears well suited for clinical use with minimal equipment, especially for GPs.

Research initiatives in hybrid-electric/sustainable aviation typically address only a single vehicle or single vehicle class. However, it can be expected that for novel propulsion and energy solutions to reach a sufficient maturity level an approach not too different from the early days of aviation could be followed: starting small to prove a technology and gradually scaling it up to larger and larger classes of vehicles. Therefore, it is important to sketch a landscape of technologies and identify areas suitable for scaling, as well as limitations or challenges for development. The CHYLA project aims to contribute to the overall research and development in sustainable aviation by providing exactly this; an overview of scaling opportunities, challenges and limitations of key radical technologies where the credibility of underlying technology assumptions is an explicit factor in developing such a landscape. In CHYLA we introduce the concept of “credible aircraft design”, which refers to the influence of the uncertainty in the assumptions behind the design to quantify how realisable, or in other words, how credible, is the design. Since technical work on the project has just started, the presentation givesa general overview of the CHYLA scope, approach and objectives.&nbsp

Bronchiectasis (BE) might be frequently present in COPD but masked by COPD symptoms. We studied the relationship of clinical signs of bronchiectasis to the presence and extent of its radiological signs in patients of different COPD severity. Visit 4 data (GOLD grades 1-4) of the COSYCONET cohort was used. Chest CT scans were evaluated for bronchiectasis in 6 lobes using a 3-point scale (0: absence, 1: ≤50%, 2: >50% BE-involvement for each lobe). 1176 patients were included (61%male, age 67.3y), among them 38 (3.2%) with reported physicians' diagnosis of bronchiectasis and 76 (6.5%) with alpha1-antitrypsin deficiency (AA1D). CT scans were obtained in 429 patients. Within this group, any signs of bronchiectasis were found in 46.6% of patients, whereby ≤50% BE occurred in 18.6% in ≤2 lobes, in 10.0% in 3-4 lobes, in 15.9% in 5-6 lobes; >50% bronchiectasis in at least 1 lobe was observed in 2.1%. Scores ≥4 correlated with an elevated ratio FRC/RV. The clinical diagnosis of bronchiectasis correlated with phlegm and cough and with radiological scores of at least 3, optimally ≥5. In COPD patients, clinical diagnosis and radiological signs of BE showed only weak correlations. Correlations became significant with increasing BE-severity implying radiological alterations in several lobes. This indicates the importance of reporting both presence and extent of bronchiectasis on CT. Further research is warranted to refine the criteria for CT scoring of bronchiectasis and to determine the relevance of radiologically but not clinically detectible bronchiectasis and their possible implications for therapy in COPD patients.

The COPD Assessment Test (CAT) is in widespread use for the evaluation of patients with chronic obstructive pulmonary disease (COPD). We assessed whether the CAT items carry additional information beyond the sum score regarding COPD characteristics including emphysema. Patients of GOLD grades 1 to 4 from the COPD cohort COSYCONET (German COPD and Systemic Consequences - Comorbidities Network) with complete CAT data were included (n = 2270), of whom 493 had chest CT evaluated for the presence of emphysema. Comorbidities and lung function were assessed following standardised procedures. Cross-sectional data analysis was based on multiple regression analysis of the single CAT items against a panel of comorbidities, lung function, or CT characteristics (qualitative score, 15th percentile of mean lung density), with age, BMI and gender as covariates. This was supported by exploratory factor analysis. Regarding the relationship to comorbidities and emphysema, there were marked differences between CAT items, especially items 1 and 2 versus 3 to 8. This grouping was basically confirmed by factor analysis. Items 4 and 5, and to a lower degree 1, 2 and 6, appeared to be informative regarding the presence of emphysema, whereas the total score was not or less informative. Regarding comorbidities, similar findings as for the total CAT score were obtained for the modified Medical Research Council scale (mMRC) which was also informative regarding emphysema. Our findings suggest that the usefulness of the CAT can be increased if evaluated on the basis of single items which may be indicating the presence of comorbidities and emphysema.

In recent years the field of soft robotics has gained a lot of interest both in academia and industry. In contrast to rigid robots, which are potentially very powerful and precise, soft robots are composed of compliant materials like gels or elastomers (Rich et al., 2018; Majidi, 2019). Their exclusive composition of nearly entirely soft materials offers the potential to extend the use of robotics to fields like healthcare (Burgner-Kahrs et al., 2015; Banerjee et al., 2018) and advance the emerging domain of cooperative human-machine interaction (Asbeck et al., 2014). One material class used frequently in soft robotics as actuators are electroactive polymers (EAPs). Especially dielectric elastomer actuators (DEAs) consisting of a thin elastomer membrane sandwiched between two compliant electrodes offer promising characteristics for actuator drives (Pelrine et al., 2000). Under an applied electric field, the resulting electrostatic pressure leads to a reduction in thickness and an expansion in the free spatial directions. The resulting expansion can reach strain levels of more than 300% (Bar-Cohen, 2004). This paper presents a bioinspired worm-like crawling robot based on DEAs with additional textile reinforcement in its silicone structures. A special focus is set on the developed cylindrical actuator segments that act as linear actuators.

This paper is aimed at giving an overview of possible cooling technologies for electrical machines and their assessment for aviation applications, e.g., fan or propeller drives. The most important demand for aircraft is the minimization of the drive system weight comprising electrical machine, power electronics, and the cooling system. The potential of aluminum winding an overview about several cooling technologies with the Rankine or Brayton cycle or utilizing the phase change of the cooling fluid is given. As an alternative approach, the cooling structure inside the machine is studied. A very interesting potential was discovered with direct slot cooling (DSC) removing the heat where it is produced and, thus, simplifying the cooling system effort and its weight. Since it is one of the most promising approaches, this cooling method is studied in depth. Furthermore, it can also be combined with one of the cooling technologies discussed above.

Rationale Alterations of acid-base metabolism are an important outcome predictor in acute exacerbations of COPD, whereas sufficient metabolic compensation and adequate renal function are associated with decreased mortality. In stable COPD there is, however, only limited information on the combined role of acid-base balance, blood gases, renal and respiratory function on exacerbation risk grading. Methods We used baseline data of the COPD cohort COSYCONET, applying linear and logistic regression analyses, the results of which were implemented into a comprehensive structural equation model. As most informative parameters it comprised the estimated glomerular filtration rate (eGFR), lung function defined via forced expiratory volume in 1 s (FEV1), intrathoracic gas volume (ITGV) and (diffusing capacity for carbon monoxide (DLCO), moreover arterial oxygen content (CaO2), partial pressure of oxygen (PaCO2), base exess (BE) and exacerbation risk according to GOLD criteria. All measures were adjusted for age, gender, body-mass index, the current smoking status and pack years. Results 1506 patients with stable COPD (GOLD grade 1–4; mean age 64.5 ± 8.1 y; mean FEV1 54 ± 18 %predicted, mean eGFR 82.3 ± 16.9 mL/min/1.73 m2) were included. BE was linked to eGFR, lung function and PaCO2 and played a role as indirect predictor of exacerbation risk via these measures; moreover, eGFR was directly linked to exacerbation risk. These associations remained significant after taking into account medication (diuretics, oral and inhaled corticosteroids), whereby corticosteroids had effects on exacerbation risk and lung function, diuretics on eGFR, BE and lung function. Conclusion Even in stable COPD acid-base metabolism plays a key integrative role in COPD risk assessment despite rather small deviations from normality. It partially mediates the effects of impairments in kidney function, which are also directly linked to exacerbation risk.

The demand for alternative fueling methods to reduce the need for fossil fuels is not limited to the electrification of ground vehicles. More-electric and all-electric aircraft pose challenges, with extensive requirements in terms of power density, efficiency, safety, and environmental sustainability. This paper focuses on electrical machines and their components, especially for high-power applications like the main propulsion. The electrical machine is evaluated from different aspects, followed by a closer look at the components and materials to determine the suitability of the current standard materials and advanced technologies. Furthermore, the mechanical and thermal aspects are reviewed, including new and innovative concepts for the cooling of windings and for the use of additive manufacturing. Aircraft have special demands regarding weight and installation space. Following recent developments and looking ahead to the future, the need and the possibilities for light and efficient electrical machines are addressed. All of the approaches and developments presented lead to a better understanding of the challenges to be expected and highlight the upcoming opportunities in electrical machine design for the use of electric motors and generators in future aircraft. Several prototypes of electrical machines for smaller aircraft already exist, such as the electric drive of the Siemens powered Extra 330LE. The focus of this paper is to provide an overview of current technical possibilities and technical interrelations of high performance electric drives for aviation. A 1 MW drive is exemplified to present the possibilities for future drives for airplanes carrying a larger number of passengers. All presented techniques can also be applied to other drive power classes.

The term bronchial hyperresponsiveness is generally used to describe a heightened airway smooth muscle bronchoconstrictor response measured by bronchoprovocation testing. However, the airway also responds to inflammation or bronchoprovocation with increased mucus secretion. We use the term “secretory hyperresponsiveness” to mean increased mucus secretion either intrinsically or in response to bronchoprovocation. This is not the same as retained phlegm or sputum. Unlike smooth muscle contraction, which is rapidly reversible using a bronchodilator, mucus hypersecretion produces airflow limitation that reverses more slowly and depends upon secretion clearance from the airway. Certain groups of patients appear to have greater mucus secretory response, including those with middle lobe syndrome, cough-dominant (”cough-variant”) asthma, and severe asthma. Secretory hyperresponsiveness also is a component of forms of lung cancer associated with bronchorrhea. An extreme form of secretory hyperresponsiveness may lead to plastic bronchitis, a disease characterized by rigid branching mucus casts that obstruct the airway. Secretory hyperresponsiveness and mucus hypersecretion appear to be related to activation of the extracellular-regulated kinase 1/2, signaling through the epidermal growth factor receptor, or secretory phospholipases A2. Recognizing secretory hyperresponsiveness as a distinct clinical entity may lead to more effective and targeted therapy for these diseases.

Vorausschauende Betriebsstrategien können den ohnehin geringen Kraftstoffverbrauch von Plug-In-Hybridfahrzeugen (PHEV) weiter senken. Sie weisen jedoch häufig einen hohen Ressourcenbedarf sowie eine hohe Sensitivität für auf der Fahrstrecke auftretende Störungen auf. Im Rahmen der vorliegenden Arbeit wird deswegen untersucht, wie sich unterschiedliche auf der Fahrstrecke auftretende Störungen, wie beispielsweise unvorhergesehene Verkehrsbehinderungen, auf das Kraftstoffeinsparpotential von vorausschauenden PHEV-Betriebsstrategien auswirken. Weiter wird untersucht, inwieweit bereits weniger komplexe und ressourcenaufwändige Betriebsstrategie-Ansätze eine signifikante Kraftstoffeinsparung herbeiführen können und wo dies nur mittels komplexer Ansätze möglich ist. Dazu wurde eine Benchmark-Studie durchgeführt in deren Zuge die Leistung dreier Software-Ansätze zur Betriebsstrategie-Optimierung in verschiedenen Testszenarien simulativ verglichen wurde. Als am wenigsten komplexer Software-Ansatz kam dabei ein nicht vorausschauender, regelbasierter Betriebsstrategie-Optimierer zum Einsatz. Weiterhin wurde ein vorausschauender für die Verwendung im Fahrzeug optimierter ressourceneffizienter Ansatz, sowie – als Benchmark – ein vorausschauender idealer Betriebsstrategie-Optimierer evaluiert. Die verwendeten Betriebsstrategie-Optimierer sowie die genutzte Simulationsumgebung wurden dabei im Rahmen der vorliegenden Arbeit entwickelt. Die erlangten Daten wurden anschließend stichprobenartig im Fahrversuch validiert. Eine hohe praktische Aussagekraft der Simulations- und Messergebnisse wurde zum einen dadurch erreicht, dass für die Simulationsdurchführung besonders praxisrelevante Testszenarien gewählt wurden. Zum anderen wurde die Auslegung der verwendeten Betriebsstrategie-Optimierer direkt anhand eines für die Simulation und die Fahrversuche herangezogenen seriennahen PHEV-Prototypen vorgenommen. Mit den so gewonnenen Erkenntnissen werden in einem Ausblick schließlich Verbesserungspotentiale an vorausschauenden PHEV-Betriebsstrategien hinsichtlich Ressourceneffizienz als auch Robustheit gegenüber auftretenden Störungen abgeleitet. Auch werden mögliche weitergehende Untersuchungen vorgeschlagen., Predictive operating strategies can further reduce the already low fuel consumption of plug-in hybrid vehicles (PHEVs). However, they often have a high resource requirement and a high sensitivity to disturbances occurring on the route. Therefore, the present study investigates how different disturbances occurring on the route, such as unforeseen traffic obstructions, affect the fuel saving potential of predictive PHEV operation strategies. Furthermore, it is investigated to what extent already less complex and resource-intensive operating strategy approaches can bring about significant fuel savings and where this is only possible by means of complex approaches. For this purpose, a benchmark study was carried out during which the performance of three software approaches for operating strategy optimization was simulatively compared in various test scenarios. The least complex software approach used was a non-predictive, rule-based operating strategy optimizer. Furthermore, a predictive resource-efficient approach optimized for in-vehicle use was evaluated, as well as - as a benchmark - a predictive ideal operating strategy optimizer. The operating strategy optimizers used as well as the simulation environment were developed in the course of this thesis. The results from the simulations were then validated in real world driving tests. A high practical significance of the simulation and real-world evaluation results was achieved on the one hand by selecting particularly practice-relevant test scenarios for the simulation. On the other hand, the operating strategy optimizers were designed for a near-production PHEV prototype which was also used for the simulation and the driving tests. Finally, the simulation and real-world evaluation results were used to derive potential improvements to predictive PHEV operating strategies in terms of resource efficiency and robustness. Possible further research is also suggested.

Durch die immer stärker werdenden Forderungen nach effizienten und emissionsarmen Antriebslösungen, schreitet die Elektrifizierung des Verkehrssektors voran. Zur Steigerung der Reichweite eines Elektrofahrzeugs wird der Wirkungsgrad des gesamten Antriebsstranges stetig optimiert. Da gerade bei großen Zwischenkreisspannungen die Verwendung eines Multilevel-Wechselrichters zu geringeren Schaltverlusten und Rippelströmen führt, werden diese vermehrt eingesetzt. Diesen Vorteilen steht die Notwendigkeit einer Balancierung der Spannungslevel als Nachteil gegenüber. Das Gesamtsystem aus Antriebsmaschine und Multilevel-Wechselrichter weist aufgrund des diskret umschaltenden Wechselrichters sowohl eine kontinuierliche als auch eine diskrete Systemdynamik auf. Da das diskrete Verhalten einen signifikanten Einfluss auf die in den Signalen enthaltenen Rauschanteile hat, ist es für eine detaillierte Systemanalyse ratsam das diskrete Verhalten möglichst genau in der Modellierung abzubilden. Die bereits existierenden Modulationsverfahren für Multilevel-Wechselrichter betrachten nur bedingt das diskrete Verhalten des zu regelnden Systems. Einer Beschreibung des Systems durch Methoden der Regelungstechnik geht meist die Vernachlässigung oder Näherung des diskreten Verhaltens durch entsprechende Modelle voraus. Eine Möglichkeit die gesamte Systemdynamik zu berücksichtigen, ist die Theorie der schaltenden Systeme. Der Fokus der oben genannten Arbeit liegt auf der Anwendung dieser Theorie zur Modellierung des Systems aus Antriebsmaschine und Multilevel-Wechselrichter. Basierend auf dem so modellierten System wird ein Hysterese-basiertes Stromregelverfahren entwickelt, welches neben dem Erreichen und Folgen einer Stromreferenztrajektorie die Balancierung der Spannungslevel des Multilevel-Wechselrichters gewährleistet. Neben diesen Hauptforderungen werden zudem die Schaltfrequenz nach oben und die Mindesteinschaltdauer der schaltenden Bauelemente nach unten begrenzt. Das vorgestellte Verfahren wird innerhalb einer Simulationsumgebung durch Vorgabe einer Stromreferenztrajektorie und eines Drehzahlprofils hinsichtlich Regelgüte, Stromrippel und Schaltfrequenzverhalten evaluiert. Aufgrund der weiten Verbreitung der beiden Bauformen wird als Antriebsmaschine eine permanenterregte Synchronmaschine und als Multilevel-Wechselrichter ein neutral point clamped t type 3 level converter verwendet., Due to the increasing demand for efficient and low-emission drive solutions, the electrification of the transport sector is advancing. To increase the range of an electric vehicle, the efficiency of the entire drive train is constantly being optimized. Since the application of a multilevel converter leads to lower switching losses and ripple currents, especially with large DC link voltages, they are increasingly implemented. These advantages are countered by the necessity of balancing the voltage levels as a disadvantage. The overall system of drive machine and multilevel converter exhibits both continuous and discrete system dynamics due to the discrete switching converter. Since the discrete behavior has a significant influence on the noise components contained in the signals, it is advisable for a detailed system analysis to represent the discrete behavior as accurately as possible in the modeling. The already existing modulation methods for multilevel converters only consider the discrete behavior of the controlled system to a limited extent. A description of the system by methods of control engineering is usually preceded by the neglect or approximation of the discrete behavior by corresponding models. One possibility to consider the whole system dynamics is the theory of switched systems. The focus of the above work is on applying this theory to model the system of drive machine and multilevel converter. Based on the system modeled in this way, a hysteresis-based current control method is developed which, in addition to achieving and following a current reference trajectory, ensures the balancing of the voltage levels of the multilevel converter. In addition to these main requirements, the switching frequency is also upper bounded and the minimum duty cycle of the switching devices is lower bounded. The presented method is evaluated within a simulation environment by prescribing a current reference trajectory and a speed profile with respect to control performance, current ripple and switching frequency behavior. Due to the widespread use of the two designs, a permanent magnet synchronous machine is used as the drive machine and a neutral point clamped t type 3 level converter is used as the multilevel converter.