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A convenient method for the synthesis of γ-spirolactones in only 2–3 steps is described. Birch reduction of inexpensive and commercially available aromatic carboxylic acids in the presence of ethylene oxide affords hydroxy acids, which undergo direct lactonization during work-up. Suitable precursors are methyl-substituted benzoic acids, naphthoic, and dicarboxylic acids. Subsequent hydrogenation proceeds smoothly with Pd/C as catalyst and saturated γ-spirolactones are isolated in excellent yields and stereoselectivities. Thus, up to 3 new stereogenic centers can be constructed as sole diastereomers from achiral benzoic acids. Furthermore, it is possible to control the degree of saturation with Raney nickel or Wilkinson's catalyst to obtain products with 1 double bond. Overall, more than 30 new γ-spirolactones have been synthesized in analytically pure form.

The photooxygenation of 1,4-cyclohexadienes has been studied with a special focus on regio- and stereoselectivities. In all examples, only the methyl-substituted double bond undergoes an ene reaction with singlet oxygen, to afford hydroperoxides in moderate to good yields. We explain the high regioselectivities by a "large-group effect" of the adjacent quaternary stereocenter. Nitriles decrease the reactivity of singlet oxygen, presumably by quenching, but can stabilize proposed per-epoxide intermediates by polar interactions resulting in different stereoselectivities. Spiro lactams and lactones show an interesting effect on regio- and stereoselectivities of the ene reactions. Thus, singlet oxygen attacks the double bond preferentially anti to the carbonyl group, affording only one regioisomeric hydroperoxide. If the reaction occurs from the opposite face, the other regioisomer is exclusively formed by severe electrostatic repulsion in a perepoxide intermediate. We explain this unusual behavior by the fixed geometry of spiro compounds and call it a "spiro effect" in singlet oxygen ene reactions.

A convenient method for the synthesis of gamma-spirolactams in only three steps is described. Birch reduction of inexpensive and commercially available aromatic carboxylic acids in the presence of chloroacetonitrile affords nitriles in moderate to good yields. Suitable precursors are methyl-substituted benzoic acids, naphthoic, and anthroic acid. Subsequent catalytic hydrogenation proceeds smoothly with PtO2 or Raney Ni as catalysts and lactams are isolated in excellent yields and stereoselectivities. Thus, up to 3 new stereogenic centers can be constructed as sole diastereomers from achiral benzoic acids. Furthermore, it is possible to control the degree of saturation at different pressures, affording products with 0, 1, or 2 double bonds. Overall, more than 15 new gamma-spirolactams have been synthesized in analytically pure form.

Background and aim Low ejection fraction (EF) has been identified as a main risk factor for perioperative complications and mortality after coronary artery bypass grafting (CABG). The purpose of this study was to compare the efficacy and early as well as midterm outcomes of off-pump CABG (OPCAB) and conventional CABG (ONCAB) surgery in patients with reduced EF. Methods We performed a retrospective review of patient demographics, preoperative risk factors, operative and postoperative outcomes of patients with left ventricular EF (LV-EF) ≤35%, who underwent CABG at our institution between January 2015 and December 2017. Propensity score and multivariate logistic regression analysis were used to compare risk adjusted outcomes between groups. Results Overall, 111 consecutive CABG-patients with LV-EF ≤ 35% underwent either ONCAB (46 patients, 41.4%) or OPCAB surgery (65 patients, 58.6%). There was no difference in early mortality (5% vs. 7.5%, p = .64) between groups. After propensity score matching, OPCAB-patients required significantly less re-sternotomies for bleeding (20% vs. 2.5%, p = .03) and consequently received significantly less blood transfusions (57.5% vs. 32.5%, p = .03). Fewer OPCAB-patients experienced low cardiac output syndrome (22.5% vs. 42.5%, p = .06) and suffered from postoperative delirium (22.5% vs. 42.5%, p = .06). There were no differences in completeness of revascularization between groups (median 1 (1.0-1.33; 1.0-1.33) OPCAB versus median 1 (1-1.33; 0.67-2) ONCAB, p = .95). Survival after 6 months, one year and three years was similar for ONCAB- and OPCAB-patients (ONCAB 92.3%, 89.4%, and 89.4% vs. OPCAB 89.8%, 85.7%, and 82.1%; p = .403). More ONCAB-patients needed a coronary re-intervention during follow-up (8.6% vs. 2.3%, p = .402). Conclusion OPCAB-surgery is a safe and effective option for patients with reduced EF. Furthermore, it does not come at the expense of less complete revascularization or increased coronary re-intervention during early follow-up.

Significant efforts have been made in recent years to identify more environmentally benign and less hazardous alternatives to N,N-dimethylformamide (DMF) in solid-phase peptide synthesis (SPPS). Several greener solvents have been endorsed as suitable candidates yet finding a neat solvent that fully matches the qualities of DMF in SPPS has proven challenging. To this end, we recently demonstrated that green binary solvent mixtures are viable alternatives to DMF and showed that the polarity and viscosity profile of a binary solvent mixture can be used to predict its utility in SPPS. In this report, we systematically investigate how the composition of green binary solvent mixtures influences Fmoc-removal, peptide coupling and common side-reactions in SPPS and show that the purity profile is not impacted adversely in binary solvent mixtures when compared to DMF. Furthermore, we demonstrate that the sole variation of the composition of the binary solvent mixture during synthesis represents a novel and simple tool to mitigate certain side-reactions in SPPS, exemplified by suppression of Arg-lactamisation and aspartimide formation. When applied to the synthesis of the peptide therapeutic Bivalirudin on a 7.5 mmol scale, we showed that simply adjusting the solvent ratio in a single step of the synthesis significantly suppressed a problematic Arg-lactamisation side-reaction. These results underline that green binary solvent mixtures not only can replace DMF in SPPS but also provide novel solutions for mitigating common side-reactions in SPPS.

Solid-phase peptide synthesis (SPPS) enables routine synthesis of virtually any type of peptide sequence and is the preferred method for peptide synthesis in academia and the pharmaceutical industry alike. Still, SPPS typically requires significant amounts of hazardous solvents and thus suffers from a negative environmental footprint. Such drawbacks have spurred numerous initiatives for solvent substitution, reduction and recycling, and a handful solvents have recently been proposed as potential green alternatives to N,N-dimethylformamide (DMF). In this report, we recognise solvent viscosity and polarity in combination as key physicochemical parameters for SPPS and identify green binary solvent mixtures of dimethyl sulfoxide (DMSO) and 1,3-dioxolane or 2-methyl tetrahydrofuran that closely resemble DMF. In a series of reagent dissolution, resin swelling, peptide coupling and Fmoc-removal experiments we show that combining solvents offers unprecedented opportunities to predict and fine-tune the overall solvent properties for different aspects of SPPS. Lastly, the identified green binary solvent mixtures were employed for the synthesis of a range of challenging model peptides and peptide therapeutics on meaningful scale, demonstrating that binary solvent mixtures are viable green alternatives to DMF in SPPS.

Controlling settlement development, which is committed to the land-saving objective, requires precise monitoring of settlement development. This paper describes how the use of new land is related to various planning procedures in Germany. The extent to which the Federal Government, the Federal States and the municipalities contribute to land use was empirically determined on the basis of 30 representatively selected municipalities. The results of these studies show that around two thirds of Germany-wide land use is caused by municipalities within the framework of their municipal planning. Other developments resulting from planning approval procedures, for example, are driven by the Federal Government and the Federal States and contribute to one third of land use. The relatively high proportion of non-municipally induced new land use was not expected tobe as high. The result shows that efforts to save land at all spatial and planning levels are necessary in order to achieve the sustainability goals. Such investigations require comprehensive and continuously updated geometric bases for actual land use. This is the only way to measure changes in land use realistically and promptly and to verify the effects of land management. However, the ongoing methodological changes in land-use recording (geodata modelling, land-use nomenclature) and their time-delayed and different implementation in the Federal States have a negative impact on land-use monitoring.

Surgery of the aortic root in acute aortic dissection type A (AADA) remains a topic of vague evidence since the extend of dissection and surgeons' capability and interpretation of the disease vary remarkably. We aimed to interpret root operation strategies in the German Registry for Acute Aortic Dissection (GERAADA) cohort.GERAADA collected the data of 56 centers between July 2006 and June 2015. A total of 3382 patients undergoing operations for AADA were included and divided into three groups according to aortic root procedure types: supracommissural replacement (SCR), conduit replacement (CR) and valve sparing root replacement (VSRR).Patients in SCR (2425, 71.7%) were significantly older than CR (681, 20.1%) and VSRR (276, 8.2%) (63.4 vs 57.5 vs 54.2 yrs; p 0.001), more female (38.9 vs 32.0 vs 26.1%; p 0.001) and presented with less aortic regurgitation (26.3 vs 57.1 vs 56.5%; p 0.001). VSRR presented with slightly less multiple organ malperfusion (11.6 vs 12.0 vs 10.9%; p = 0.045) and were more often diagnosed for Marfan syndrome (2.4 vs 5.1 vs 9.1%; p 0.001). Thirty-day mortality was lower for VSRR (11.6%) compared to SCR (16.1%) and CR (19.8%; p = 0.010). Despite longer procedural times multivariable regression showed no influence of total arch replacement for VSRR on mortality compared to CR (OR 0.264; 95% CI, 0.033-2.117; p = 0.21).SCR remains the procedure of choice in elderly and compromised patients. Extended root preservation techniques may be applied even in combination with extended aortic arch surgery for selected patients for AADA with promising early outcomes.

Background Recurrent ventricular tachycardia (VT) can occur after left ventricular assist device (LVAD) implantation. In this case, medical treatment might be insufficient. We report a case of a left-sided thoracoscopic sympathectomy as a feasible treatment escalation in intractable VT. Case report A 72-year-old patient underwent an internal cardioverter defibrillator (ICD) implantation as primary prophylaxis for VTs in the setting of staged heart failure therapy. Afterwards, due to a progressive dilative cardiomyopathy he underwent a minimal-invasive LVAD implantation (HeartWare, Medtronic). After an uneventful minimal-invasive LVAD-implantation the patient was discharged to a rehabilitation program. However, after 7 weeks he developed recurrent VTs which were successfully terminated by ICD shocks deliveries leading to severe discomfort and frequent hospitalizations. Eventually, the patient was admitted with an electrical VT storm. Successful endocardial catheter ablation of all inducible VTs were performed combined with multiple rearrangements of his oral antiarrhythmic medication. However, all these treatments could not suppress further occurrence of VTs. After an interdisciplinary discussion the patient agreed to a left-sided video-assisted thoracoscopic sympathectomy. After a follow up of 150 days the patient was free from VTs apart from one short event. Conclusion We believe video-assisted thoracoscopic sympathectomy might be a surgical treatment option in patients with intractable recurrent VTs after catheter ablation of VT reentrant substrate even after minimal-invasive LVAD implantation.

Die postoperative herzchirurgische Therapie ist neben der Weiterentwicklung der chirurgischen Techniken ein wesentlicher Bestandteil der Optimierung der ganzheitlichen Patientenversorgung. Von den moglichen postoperativen Komplikationen sind aufgrund der hohen Inzidenz besonders Herzrhythmusstorungen hervorzuheben. Sie konnen zu hamodynamischer Instabilitat, thrombembolischen Ereignissen, verlangertem stationarem Aufenthalt und erhohter Mortalitat fuhren. Zu den haufigsten gehoren die supraventrikularen Herzrhythmusstorungen. Im Vergleich dazu sind ventrikulare Herzrhythmusstorungen seltener, jedoch lebensbedrohlich. Vorbeugen und rechtzeitiges Erkennen dieser Komplikationen sind essenziell. Der vorliegende Beitrag fasst die haufigsten postoperativen Herzrhythmusstorungen mit den verschiedenen Therapieoptionen zusammen.

Over the past two decades, building culture has increasingly caught the attention of the architectural and planning professions. The building culture is to be understood in the broadest sense as the sum of all cultural, economic, technological, social and ecological factors influencing the quality and process of planning and construction. While the revitalisation and promotion of building culture is central to discussions on urban areas, these are generally ignored in regard to rural areas. This article aims to provide an overview of how building culture has been promoted in Germany’s rural areas, thereby contributing to international research on this topic. The paper adopts a general descriptive approach in examining the promotion of building culture in rural Germany. It provides background knowledge on institutional promotion and demonstrates the diverse approaches implemented in representative villages as best practices examples. The German experience confirms that the promotion of building culture is a meaningful and effective measure to help revitalise rural areas. Moreover, the three selected rural municipalities show how stakeholders from civil society are increasingly involved in measures to implement and promote building culture in the local context.

Dispersed low-density development–“urban sprawl”–has many detrimental environmental, economic, and social consequences. Sprawl leads to higher greenhouse-gas emissions and poses an increasing threat to the long-term availability of many vital ecosystem services. Therefore, urban sprawl is in stark contradiction to the principles of sustainable land use and to the need for a sustainability transformation. This study presents the degree of urban sprawl on the planet at multiple spatial scales (continents, UN regions, countries, subnational units, and a regular grid) for the period 1990–2014. Urban sprawl increased by 95% in 24 years, almost 4% per year, with built-up areas growing by almost 28 km2 per day, or 1.16 km2 per hour. The results demonstrate that Europe has been the most sprawled and also the most rapidly sprawling continent, by 51% since 1990. At the scale of UN regions, the highest relative increases in urban sprawl were observed in East Asia, Western Africa, and Southeast Asia. Urban sprawl per capita has been highest in Oceania and North America, exhibiting a minor decline since 1990, while it has been increasing rapidly in Europe, by almost 47% since 1990. The study revealed a strong relationship between urban sprawl and the level of human development as measured by the Human Development Index (HDI). The results suggest that it will be important for a more sustainable future to find a better balance between a high quality of life and using land more sparingly. There is an urgent need to stop urban sprawl, since current regulations and measures in developed countries are apparently not effective at limiting it. Monitoring urban sprawl can serve to guide policy development such as the implementation of targets and limits and to evaluate the effectiveness of urban growth management strategies at mitigating urban sprawl.

The development of bioresorbable materials for temporary implantation enables progress in medical technology. Iron (Fe)-based degradable materials are biocompatible and exhibit good mechanical properties, but their degradation rate is low. Aside from alloying with Manganese (Mn), the creation of phases with high electrochemical potential such as silver (Ag) phases to cause the anodic dissolution of FeMn is promising. However, to enable residue-free dissolution, the Ag needs to be modified. This concern is addressed, as FeMn modified with a degradable Ag-Calcium-Lanthanum (AgCaLa) alloy is investigated. The electrochemical properties and the degradation behavior are determined via a static immersion test. The local differences in electrochemical potential increase the degradation rate (low pH values), and the formation of gaps around the Ag phases (neutral pH values) demonstrates the benefit of the strategy. Nevertheless, the formation of corrosion-inhibiting layers avoids an increased degradation rate under a neutral pH value. The complete bioresorption of the material is possible since the phases of the degradable AgCaLa alloy dissolve after the FeMn matrix. Cell viability tests reveal biocompatibility, and the antibacterial activity of the degradation supernatant is observed. Thus, FeMn modified with degradable AgCaLa phases is promising as a bioresorbable material if corrosion-inhibiting layers can be diminished.

Multiple, site-specific protein conjugation is increasingly attractive for the generation of antibody-drug conjugates (ADCs). As it is important to control the number and position of cargoes in an ADC, position-selective generation of reactive sites in the protein of interest is required. Formylglycine (FGly) residues are generated by enzymatic conversion of cysteine residues embedded in a certain amino acid sequence motif with a formylglycine-generating enzyme (FGE). The addition of copper ions increases FGE activity leading to the conversion of cysteines within less readily accepted sequences. With this tuned enzyme activity, it is possible to address two different recognition sequences using two aerobic formylglycine-generating enzymes. We demonstrate an improved and facile strategy for the functionalization of a DARPin (designed ankyrin repeat protein) and the single-chain antibody scFv425-Fc, both directed against the epidermal growth factor receptor (EGFR). The single-chain antibody was conjugated with monomethyl auristatin E (MMAE) and carboxyfluorescein (CF) and successfully tested for receptor binding, internalization, and cytotoxicity in cell culture, respectively.

During our transthoracic echocardiography (TTE) courses, medical students showed difficulty in spatial orientation. We implemented the use of 3D printed cardiac models of standard TTE views PLAX, PSAX, and A4C and assessed their efficacy in TTE-teaching.One hundred fifty-three participants were split into two groups. A pre-test-retest of anatomy, 2D -, and 3D orientation was conducted. The intervention group (n = 77) was taught using 3D models; the control group (n = 76) without. Both were comparable with respect to baseline parameters. Besides test-scores, a Likert scale recorded experiences, difficulties, and evaluation of teaching instruments.From the 153 students evaluated, 123 improved, 20 did worse, and ten achieved the same result after the course. The median overall pre-test score was 29 of 41 points, and the retest score was 35 (p 0.001). However, the intervention group taught with the 3D models, scored significantly better overall (p = 0.016), and in 2D-thinking (p = 0.002) and visual thinking (p = 0.006) subtests. A backward multivariate linear regression model revealed that the 3D models are a strong individual predictor of an excellent visual thinking score. In addition, our study showed that students with difficulty in visual thinking benefited considerably from the 3D models.Students taught using the 3D models significantly improved when compared with conventional teaching. Students regarded the provided models as most helpful in their learning process. We advocate the implementation of 3D-printed heart models featuring the standard views for teaching echocardiography. These findings may be transferable to other evidence based medical and surgical teaching interventions.

For many applications, implants overtake body function for a certain time. Bioresorbable implants reduce patient burden as they prevent adverse consequences due to remaining implants or operations for removal. Such materials are in clinical use but do not fulfill the requirements of all applications. Iron (Fe) is promising to develop further bioresorbable materials as it offers biocompatibility and good mechanical properties. Alloying, e.g., with manganese (Mn), is necessary to adapt the mechanical behavior and the degradation rate. However, the degradation rate of FeMn is too low. The creation of phases with high electrochemical potential evokes anodic dissolution of the FeMn, increasing the degradation rate. Therefore, silver (Ag), which is insoluble with Fe, has high potential, is biocompatible, and offers antibacterial properties, can be used. Powder-based processes such as laser beam melting (LBM) are favorable to process such immiscible materials. A degradable Ag alloy has to be used to enable the dissolution of Ag phases after the FeMn. This study reports first about the successful processing of FeMn with 5 wt.% of a degradable Ag–calcium–lanthanum (AgCaLa) alloy and enables further targeted adaption due to the gained understanding of the effects influencing the morphology and the chemical composition of the Ag phases.

Acute aortic Stanford type A dissection remains a frequent and life-limiting event for patients with Marfan syndrome. Outcome results in this high-risk group are limited.The German Registry for Acute Aortic Dissection Type A collected the data of 56 centers between July 2006 and June 2015. Of 3385 patients undergoing operations for acute aortic Stanford type A dissection, 117 (3.5%) were diagnosed with Marfan syndrome. We performed a propensity score match comparing patients with Marfan syndrome with patients without Marfan syndrome in a 1:2 fashion.Patients with Marfan syndrome were significantly younger (42.9 vs 62.2 years; P .001), predominantly male (76.9% vs 62.9%; P = .002), and less catecholamine dependent (9.4% vs 20.3%; P = .002) compared with the unmatched cohort. They presented with aortic regurgitation (41.6% vs 23.0%; P .001) and involvement of the supra-aortic vessels (50.4% vs 39.5%; P = .017) more often. Propensity matching revealed 82 patients with Marfan syndrome (21 female) with no significant differences in baseline characteristics compared with patients without Marfan syndrome (n = 159, 36 female; P = .607). Although root preservation was more frequent in patients with Marfan syndrome, procedure types did not differ significantly (18.3% vs 10.7%; P = .256). Aortic arch surgery was performed more frequently in matched patients (87.5% vs 97.8%; P = .014). Thirty-day mortality did not differ between patients with and without Marfan syndrome (19.5% vs 20.1%; P = .910). Multivariate regression showed no influence of Marfan syndrome on 30-day mortality (odds ratio, 0.928; 95% confidence interval, 0.346-2.332; P = .876).Marfan syndrome does not adversely affect 30-day outcomes after surgical repair for acute aortic Stanford type A dissection compared with a matched cohort. Long-term outcome analysis is needed to account for the influence of further downstream interventions.

Im Dezember 2015 traten die Gesellschafter Dr. Michael Otto und Benjamin Otto sowie die sieben damaligen Vorstande der Otto Group vor alle MitarbeiterInnen des Konzerns. Sie stiesen damit die tiefgreifendste Veranderung in der 70-jahrigen Unternehmensgeschichte an: Den Kulturwandel 4.0. Dieser fordert und fordert das Umdenken bisheriger Denk- und Verhaltensweisen, um die (Zusammen-)Arbeit im Konzern nachhaltig zu verandern und den Erfolg zu sichern. Der Kulturwandel 4.0 erfordert Kraft, um alle Unsicherheiten und Herausforderungen, die im Prozess unweigerlich verankert sind, auszuhalten. In diesem Beitrag werden die Herangehensweise an einen solchen umfassenden Veranderungsprozess und die dazugehorigen Herausforderungen beschrieben sowie erste Best Practices und Erkenntnisse hinsichtlich moglicher Erfolgsfaktoren skizziert. Deutlich wird, dass die digitale Transformation weit mehr mit sich bringt als technologische Veranderungen. Dies wird auch an einem Beispiel des stationaren Einzelhandels beschrieben.

Spatestens seit den 1950er und 1960er Jahren hat die Literaturwissenschaft – namentlich durch das im New Criticism propagierte Verfahren des close reading – ein Interesse an den Mikrostrukturen literarischer Texte entwickelt. Bis heute gehort die Analyse stilistischer und semantischer Nuancen zur literaturwissenschaftlichen Praxis. Trotzdem hat sich erst in den letzten Jahren, im Zuge einer zunehmenden Beschaftigung mit der Schriftlichkeit der Literatur, eine systematische Forschung zur Interpunktion und Zeichensetzung etabliert.

The aim was to evaluate the incidence of stroke in the setting of cardiac surgery with or without hemodynamically relevant asymptomatic carotid stenosis contralateral to the occlusion. We designed a historical cohorts study, focused on patients with unilateral totally occluded internal carotid arteries who were referred for any cardiac surgery at our center. Isolated unilateral occlusions were assigned to group 1 (n = 60), and those with a contralateral stenosis grade ≥ 60% were included in group 2 (n = 51). A total of 111 patients operated in our center from 1997 to 2016 were included. Patients in group 2 had an asymptomatic contralateral internal carotid artery stenosis with a mean stenosis grade of 71 ± 20%. Simultaneous carotid endarterectomy (CEA) was performed in 22 patients from group 2. The overall mortality was 8/111 (7.2%). Carotid-associated mortality was not observed, whereas an overall stroke incidence of 8/111 (7.2%) was detected. The group-related outcome showed comparable results for mortality (group 1: 4/60 (6.7%) vs. group 2: 4/51 (7.8%); p = 1.0). Regarding stroke incidence, group 2 had a higher incidence of overall strokes (2/60 (3.3%) vs. 6/51 (11.8%); p = 0.14) with more contralateral (0/60 (0%) vs. 2/51 (3.9%); p = 0.209) and ipsilateral strokes (2/60 (3.3%) vs. 4/51 (7.8%); p = 0.411). Stroke rate peaked in patients with simultaneous carotid and cardiac surgery (n = 22; 18.2%; p = 0.048). Performing simultaneous CEA during cardiac surgery in the presence of a contralateral occlusion may promote stroke. Asymptomatic contralateral carotid stenosis is a risk factor for stroke in patients with carotid occlusion prior to cardiac surgery.

l-Amino acid oxidases (LAAOs) are flavoproteins, which use oxygen to deaminate l-amino acids and produce the corresponding α-keto acids, ammonia, and hydrogen peroxide. Here we describe the heterologous expression of LAAO4 from the fungus Hebeloma cylindrosporum without signal sequence as fusion protein with a 6His tag in Escherichia coli and its purification. 6His-hcLAAO4 could be activated by exposure to acidic pH, the detergent sodium dodecyl sulfate, or freezing. The enzyme converted 14 proteinogenic l-amino acids with l-glutamine, l-leucine, l-methionine, l-phenylalanine, l-tyrosine, and l-lysine being the best substrates. Methyl esters of these l-amino acids were also accepted. Even ethyl esters were converted but with lower activity. Km values were below 1 mM and vmax values between 19 and 39 U mg−1 for the best substrates with the acid-activated enzyme. The information for an N-terminal aldehyde tag was added to the coding sequence. Co-expressed formylglycine-generating enzyme was used to convert a cysteine residue in the aldehyde tag to a Cα-formylglycine residue. The aldehyde tag did not change the properties of the enzyme. Purified Ald-6His-hcLAAO4 was covalently bound to a hexylamine resin via the Cα-formylglycine residue. The immobilized enzyme could be reused repeatedly to generate phenylpyruvate from l-phenylalanine with a total turnover number of 17,600 and was stable for over 40 days at 25 °C.

Human settlements are mainly formed by buildings with their different characteristics and usage. Despite the importance of buildings for the economy and society, complete regional or even national figures of the entire building stock and its spatial distribution are still hardly available. Available digital topographic data sets created by National Mapping Agencies or mapped voluntarily through a crowd via Volunteered Geographic Information (VGI) platforms (e.g. OpenStreetMap) contain building footprint information but often lack additional information on building type, usage, age or number of floors. For this reason, predictive modeling is becoming increasingly important in this context. The capabilities of machine learning allow for the prediction of building types and other building characteristics and thus, the efficient classification and description of the entire building stock of cities and regions. However, such data-driven approaches always require a sufficient amount of ground truth (reference) information for training and validation. The collection of reference data is usually cost-intensive and time-consuming. Experiences from other disciplines have shown that crowdsourcing offers the possibility to support the process of obtaining ground truth data. Therefore, this paper presents the results of an experimental study aiming at assessing the accuracy of non-expert annotations on street view images collected from an internet crowd. The findings provide the basis for a future integration of a crowdsourcing component into the process of land use mapping, particularly the automatic building classification.

Implants often overtake body function just for a certain time and remain as an unnecessary foreign body or have to be removed. Thus, resorbable implants are highly beneficial to reduce patient burden. Besides established materials, Iron-(Fe)-based alloys are in focus due to superior mechanical properties and good biocompatibility. However, their degradation rate needs to be increased. Phases with high electrochemical potential could promote the dissolution of residual material based on the galvanic coupling. Silver (Ag) is promising due to its high electrochemical potential (+0.8 V vs. SHE), immiscibility with Fe, biocompatibility, and anti-bacterial properties. But to prevent adverse consequences the Ag-particles, remaining after dissolution of the matrix, need to dissolve. Thus, a bioresorbable Ag-alloy is required. Regarding the electrochemical potential and degradation behavior of binary alloys, Cerium (Ce) and Lanthanum (La) are well-suited considering their biocompatibility and antibacterial behavior. Accordingly, this research addresses AgCe and AgCeLa alloys as additives for Fe-based materials with adapted degradation behavior. Furthermore, degradable Ag-alloys combined with inert implant materials could enable the controlled release of antibacterial active Ag-ions.

A large share of urban land is dedicated to commercial and industrial activities. While this is considered key for economic development, the contribution of such areas to urban expansion has also been strongly criticised from environmental and societal perspectives. Clearly, the interrelations between economic activity and land use are highly relevant to planning and policy development. Yet relatively little is known about patterns of commercial and industrial land at the level of city regions and their effect on economic development. The goal of this contribution is to present an empirical approach for analysing the development of commercial and industrial land within city regions and to place this in a socio-economic context. We argue that land provision at suitable (i.e. central) locations has a positive effect on employment. To test this hypothesis, we investigate relevant land use changes by analysing processed topographic land use data and location by centrality in regional road networks, using the example of city regions in southern Germany for the period 2006–2018. Our results reveal regional patterns of distinct spatial and socio-economic trends that indicate suburbanisation processes and the emergence of polycentric patterns. While employed is closely correlated with absolute change in land in both large and small regions, the correlation between location and employment decreases with the size of regions. The results confirm the viability of the chosen approach to illuminate processes within functionally-interlinked city regions and promote a discussion of cause-effect relationships between the provision of commercial/industrial areas and employment.

OBJECTIVES Preventing type A aortic dissection requires reliable prediction. We developed and validated a multivariable prediction model based on anthropometry to define patient-adjusted thresholds for aortic diameter and length. METHODS We analysed computed tomography angiographies and clinical data from 510 control patients, 143 subjects for model validation, 125 individuals with ascending aorta ectasia (45–54 mm), 58 patients with aneurysm (≥55 mm), 206 patients with type A aortic dissection and 19 patients who had received a computed tomography angiography ≤2 years before they suffered from a type A aortic dissection. Computed tomography angiographies were analysed using curved planar reformations. RESULTS In the control group, the mean ascending aortic diameter was 33.8 mm [standard deviation (SD) ±5.2 mm], and the length, measured from the aortic valve to the brachiocephalic trunk, was 91.9 mm (SD ±12.2 mm); both diameter and length were correlated with anthropometric parameters and were smaller than the respective values in all pathological groups (P 25% in the ectasia and aneurysm groups. CONCLUSIONS The regression model provides a patient-adjusted prediction of the thresholds for aortic diameter and length. In our retrospective data, the model resulted in better identification of aortas at the risk of dissection than the conventional 55-mm diameter threshold. The model is available as an Internet calculator (www.aorticcalculator.com).

Im Dezember 2015 traten die Gesellschafter Dr. Michael und Benjamin Otto sowie die sieben damaligen Vorstande der Otto Group auf einer Veranstaltung in der Hamburger Konzernzentrale vor mehreren hundert Mitarbeitern. Sie stiesen dort einen Prozess an, der die tief greifendste Veranderung in der 70-jahrigen Unternehmensgeschichte werden sollte: Den Kulturwandel 4.0. Dieser fordert und fordert das Umdenken bisheriger Denk- und Verhaltensweisen aller Mitarbeiterinnen und Mitarbeiter, um die (Zusammen-)arbeit im Konzern nachhaltig zu verandern. Und er erfordert Kraft, um alle Unsicherheiten und Herausforderungen, die im Prozess unweigerlich verankert sind, auszuhalten. In diesem Beitrag werden die Herangehensweise an einen solchen umfassenden Veranderungsprozess und dazugehorige Herausforderungen beschrieben, sowie erste Best Practices und Erkenntnisse hinsichtlich moglicher Erfolgsfaktoren skizziert.

OBJECTIVES There is an ongoing discussion about how to treat coronary stents during bypass surgery: Should patent stents be left alone and the stented vessels be ungrafted, or should every stented coronary artery receive a bypass graft? This study aims to determine the relevance of perioperative stent stenosis or occlusion on postoperative outcomes up to 3 years postoperatively. METHODS Patients undergoing coronary artery bypass grafting surgery (CABG) (±concomitant procedures) with previous percutaneous coronary intervention from 4 centres were prospectively included in this observatory study between April 2015 and June 2017. A coronary angiography was conducted between the fifth and seventh postoperative days. The preoperative and postoperative angiograms were assessed in a core laboratory, assessing the patencies of coronary stents and bypass grafts. The core lab investigators were blinded to the patients’ characteristics and perioperative course. RESULTS A total of 107 patients were included in the study. In the postoperative coronary angiography, 265 bypass grafts and 189 coronary stents were examined angiographically. Ninety-seven percent of preoperatively patent stents remained patent. New coronary stent stenoses were observed in 5 patients (4.7%). All 5 patients were asymptomatic and managed conservatively. Bypass stenoses were observed in 12 patients (11%), of whom were managed conservatively, 4 underwent percutaneous coronary intervention and 1 underwent redo-CABG. Two years postoperatively, 97% of patients were alive. Patients with new stent stenosis tended to have a better survival compared with patients with bypass stenosis (100% vs 73%; P = 0.09) up to 3 years postoperatively. CONCLUSIONS Perioperative coronary stent stenosis occurs rarely. It is safe to leave a patently stented coronary vessel without bypass grafting.

Resorbable implants are highly beneficial to reduce patient burden since they need not be removed after a defined period. Currently, magnesium (Mg) and polymers are being applied as bioresorbable materials. However, for some applications the insufficient mechanical properties and high degradation rate of Mg cause the need for new materials. Iron (Fe)-based alloys are promising due to their biocompatibility and good mechanical properties, but their degradation rate is too low and needs to be adapted eg. via alloying with manganese (Mn). Besides, phases with high electrochemical potential lead to increased degradation of residual material with lower potential based on the galvanic coupling. Here, silver (Ag) is promising for the formation of such phases due to its high electrochemical potential (+0.8 V vs. SHE), immiscibility with Fe, biocompatibility, and anti-bacterial properties. Since remaining silver particles can lead to adverse consequences as thrombosis, these particles need to dissolve after the matrix material. Thus a silver alloy with high electrochemical potential, biocompatibility, and adjusted degradation behavior is required as an additive for iron-based bioresorbable materials. Several silver alloying systems are possible, but regarding the electrochemical potential and degradation behavior of binary alloys, calcium (Ca) and lanthanum (La) are best-suited considering their biocompatibility. Accordingly, this research addresses AgCa and AgCaLa alloys as additives for iron-based degradable materials with adapted degradation behavior

OBJECTIVES We measured aortic dimensions, particularly length parameters, using 3D imaging with the aim of refining the risk-morphology for Stanford type A aortic dissection (TAD). METHODS Computer tomography angiography studies were analysed using the curved multiplanar reformats. At defined landmarks, the diameters and lengths of aortic segments were recorded. Three groups were compared retrospectively: patients actually suffering from a TAD (TAD-group; n = 150), patients before suffering a TAD (preTAD-group n = 15) and a healthy control group ( n = 215). Receiver operating characteristic curves (ROCs) were analysed (control versus preTAD) to study the diagnostic value of the individual variables. RESULTS Median diameters of preTAD (43 mm) and TAD (50 mm) aortas were significantly ( P

The catheter-based Impella 5.0 left ventricular assist device is a powerful and less invasive alternative for patients in cardiogenic shock. The use as second-line therapy in patients with precedent extracorporeal life support (ECLS) has not been described before now. We analyzed our experience of consecutive patients treated with this alternative strategy. From April 2014 to December 2014, eight patients had been implanted as a second-line option after ECLS support. The reason for the change from ECLS to Impella 5.0 was absence of cardiac recovery for primary weaning and complications of ECLS therapy. The mean time of ECLS support prior to Impella implantation was 12 ± 7 days. The implantation of the Impella 5.0/CP was technically successful in all patients, and the ECLS could be explanted in all eight patients who received Impella implantation as a second-line treatment. The second-line Impella 5.0 therapy resulted in two patients who turned into left ventricular assist device (LVAD) candidates, two primary weaning candidates, and four patients who died in the setting of sepsis or absent cardiac recovery and contraindications for durable LVAD therapy. Thereby, the overall hospital discharge survival as well as the 180-day survival was 50% for Impella 5.0 implantations as second-line procedure after ECLS. The latest follow-up survival of this second-line strategy after ECLS was three out of eight, as one patient died after 299 days of LVAD support due to sepsis. The use of Impella 5.0 constitutes a possible second-line therapeutic option for those patients who do not show cardiac recovery during prolonged ECLS support or suffer from complications of ECLS therapy. This treatment allows additional time for decisions regarding cardiac recovery or indication for durable LVAD therapy.

Background: Cardiovascular diseases are the leading cause of death worldwide. Particularly aortic aneurysms are problematic and underdiagnosed: Existing diagnostic techniques either lack sensitivity or require specialized expertise, are invasive and costly which hampers effective screening. The objective of this proof-of-concept study is to develop an easy-to-use, non-invasive diagnostic method to generate suspicious facts about the presence of aortic aneurysms at the family physician level. This study is based on previous in-silico results and reports on the first clinical study ever to validate attempts to diagnose aortic aneurysms using machine learning techniques. Method: Two feature selection approaches for a classification “control group vs. aneurysms in the thoracic or abdominal aorta“ using Naive Bayes and K-Nearest-Neighbor-algorithms were applied to in-vivo data from a clinical study including 55 patients. The first attempt based on parameter estimation of AutoRegressive-MovingAverage (ARMAX)-models, the second on frequency response of the transfer function, both computed using two peripheral photoplethysmographic signals. Results: In both cases only around 60% overall accuracy was achieved, but as classifiers trained and tested with randomly permuted labels show less accuracy, an intrinsic effect of aneurysms could be verified. Compared to previous in-silico results, the lower accuracy can be explained by low signal-to-noise ratio of the sensors used in connection with the low peripheral perfusion of the highly morbid patients, variability and number of patients in the clinical study. Conclusion: Both approaches have shown basic classification quality in a proof-of-concept clinical setting, however to overcome remaining uncertainties, training of the classifier with a larger number of patients is necessary. Nevertheless, we assume, that the method will improve the interpretation of cardiovascular signals in the early diagnosis of aortic aneurysms in near future. (clinical study approved by Ethics Committee, University Hospital Tubingen (Germany) (No. 136/2018801)).

Purpose:C-reactive protein (CRP) and white blood cell (WBC) count are routine blood chemistry parameters in monitoring infection. Little is known about the natural history of their serum levels in conservative and operative spondylodiscitis treatment.Methods:Pre- and postoperative serum levels of CRP and WBC count in 145 patients with spondylodiscitis were retrospectively assessed. One hundred and four patients were treated by debridement, spondylodesis, and an antibiotic regime, 41 only with a brace and antibiotics. The results of the surgical group were compared to 156 patients fused for degenerative disc disease (DDD).Results:Surgery had a significant effect on peak postoperative CRP levels. In surgically managed patients, CRP peaked at 2–3 days after surgery (spondylodiscitis: pre-OP: 90 mg/dl vs. post-OP days 2–3: 146 mg/dl; DDD: 9 mg/dl vs. 141 mg/dl; p < 0.001), followed by a sharp decline. Although values were higher for spondylodiscitis patients, dynamics of CRP values were similar in both groups. Nonoperative treatment showed a slower decline. Surgically managed spondylodiscitis showed a higher success rate in identifying bacteria. Specific antibiotic treatment led to a more predictable decline of CRP values. WBC did not show an interpretable profile.Conclusion:CRP is a predictable serum parameter in patients with spondylodiscitis. WBC count is unspecific. Initial CRP increase after surgery is of little value in monitoring infection. A preoperative CRP value, and control once during the first 3 days after surgery is sufficient. Closer monitoring should then be continued. Should a decline not be observed, therapy needs to be scrutinized, antibiotic treatment reassessed, and concomitant infection contemplated.

Background Emergency coronary artery bypass grafting (CABG) in the setting of acute coronary syndrome (ACS) has been associated with increased morbidity and mortality. Avoiding cardiopulmonary bypass might be advantageous, but the role of off-pump CABG (OPCAB) remains controversial, as it has been associated with incomplete revascularization in several studies. The objective of this study was to evaluate the feasibility, efficacy, and outcome of OPCAB surgery in ACS patients. Methods We performed a retrospective review of ACS patients who underwent on-pump CABG (ONCAB) or OPCAB, either emergently or delayed, at our institution. Results Between January 2015 and December 2016, a total of 205 consecutive ACS patients underwent either ONCAB (109 patients, 53.2%) or OPCAB surgery (96 patients, 46.8%). EuroSCORE II levels (5.6 ± 7.2 vs 4.9 ± 6.5, p = 0.226) and demography were comparable between groups.A trend towards lower postoperative mortality was observed in OPCAB patients (2.1 vs 5.5%). The incidence of postoperative stroke and low cardiac output syndrome, as well as the duration of inotropic support and the need for re-sternotomy, was significantly lower in the OPCAB group (p CABG performed instantly in an emergency situation was not associated with increased mortality or morbidity when compared with delayed procedures, and OPCAB surgery in emergency patients was associated with lower postoperative morbidity and shorter stays in the intensive care unit (p There were no differences in completeness of revascularization between groups (median 1 [1–1.33;0.33–1.67] OPCAB versus median 1 (1–1.33;0.67–2) ONCAB, p = 0.617), even in the emergency setting. Conclusion OPCAB surgery is safe and effective in ACS and may be considered in hemodynamically stable patients in the emergency setting.