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Since 2010, an intensified ambulatory cardiology care programme has been implemented in southern Germany. To improve patient management, the structure of cardiac disease management was improved, guideline-recommended care was supported, new ambulatory medical services and a morbidity-adapted reimbursement system were set up. Our aim was to determine the effects of this programme on the mortality and hospitalisation of enrolled patients with cardiac disorders. We conducted a comparative observational study in 2015 and 2016, based on insurance claims data. Overall, 13,404 enrolled patients with chronic heart failure (CHF) and 19,537 with coronary artery disease (CAD) were compared, respectively, to 8,776 and 16,696 patients that were receiving usual ambulatory cardiology care. Compared to the control group, patients enrolled in the programme had lower mortality (Hazard Ratio: 0.84; 95% CI: 0.77–0.91) and fewer all-cause hospitalisations (Rate Ratio: 0.94; 95% CI: 0.90–0.97). CHF-related hospitalisations in patients with CHF were also reduced (Rate Ratio: 0.76; 95% CI: 0.69–0.84). CAD patients showed a similar reduction in mortality rates (Hazard Ratio: 0.81; 95% CI: 0.76–0.88) and all-cause hospitalisation (Rate Ratio: 0.94; 95% CI: 0.91–0.97), but there was no effect on CAD-related hospitalisation. We conclude that intensified ambulatory care reduced mortality and hospitalisation in cardiology patients.
Das Staatsangehörigkeitsrecht verankert rechtlich Vorstellungen über Zugehörigkeit und bestimmt wer vollumfängliche Rechte in einer Gesellschaft hat und wer nicht. Jahrzehntelang wurde Migration in Deutschland als etwas temporäres betrachtet. Im Staatsangehörigkeitsrecht galt bis zur Reform 1999/2000 weitgehend das „ius sanguinis“, das Abstammungsrecht, das auf einem rassistischen und völkischen Staatsverständnis beruht. Diese Reform bedeutete somit mehr als eine reine Gesetzesänderung. Sie war eine Anerkennung Deutschlands als Einwanderungsland und die Veränderung der Vorstellung deutscher Identität. Als Reaktion entbrannte infolge der Reformpläne eine hitzige, rassistische Debatte in der Öffentlichkeit über ebendiese Fragen, die unter dem polarisierten Schlagwort „Doppelpass“ verhandelt wurde. Es war die lauteste migrationspolitische Debatte dieser Zeit.
Kurze Zeit vor Beginn dieser Debatte war die rechtsterroristische Gruppe „Nationalsozialistischer Untergrund“ (NSU) abgetaucht, um einem Haftbefehl zu entgehen. Der NSU war ein deutsches, neonazistisches Netzwerk, in dessen Mittelpunkt drei Terrorist*innen standen. Sie verübten über einen Zeitraum von zwölf Jahren eine rassistische Mordserie an neun Personen türkischer, kurdischer und griechischer Herkunft sowie drei Sprengstoffanschläge auf migrantische Orte und ermordeten eine Polizistin. Den ersten ihrer Sprengstoffanschläge begingen sie nur einen Monat nach der Unterzeichnung der Reform. Wenige Monate nach dem Inkrafttreten des Gesetzes begannen sie mit dem Anschlag auf Enver Şimşek ihre rassistische Mordserie.
Diese Arbeit untersucht anhand der Struktur der Historisch-Materialistischen Politikanalyse das Migrationsregime um die Staatsangehörigkeitsreform von 1999/2000 und wie der NSU darin verortet werden kann.
Die Kontextanalyse stellt auf der Grundlage einer Literaturrecherche die relevanten historischen und strukturellen Faktoren der Debatte sowie des NSU dar. Im nächsten Schritt werden mithilfe einer Analyse von Zeitungsartikel aus dieser Zeit die relevanten Akteur*innen identifiziert und in die vier Hegemonieprojekte neoliberal, sozial, linksliberal-alternativ und konservativ gruppiert. Darauffolgend wird der Ablauf der Debatte in vier Phasen darstellt und als Aushandlung der vier Hegemonieprojekte rekonstruiert. Dabei zeigt sich, dass kein Projekt sich vollumfänglich durchsetzen und Hegemonie erreichen konnte, sie jedoch unterschiedlich stark in den Medien repräsentiert wurden.
Im letzten Schritt betrachtet diese Arbeit Verbindungen dieser Migrationsregime-Analyse zum NSU. Sie kommt zu dem Ergebnis, dass der NSU kein Akteur im Migrationsregime um die Staatsangehörigkeitsdebatte von 1998/99 war. Aufgrund der geringen Erkenntnisse über spezifische Meinungen des NSU zum Staatsangehörigkeitsrecht, können keine kausalen Beziehungen hergestellt werden. Dennoch zeigt diese Arbeit Gemeinsamkeiten in den Weltbildern, Annahmen und migrationspolitischen Zielen des NSU, des konservativen Hegemonieprojektes sowie Teilen der Bevölkerung auf. Dadurch wird ein Beitrag dazu geleistet den NSU als Produkt und Teil der deutschen Gesellschaft zu begreifen.
Our knowledge of early evolution of snakes is improving, but all that we can infer about the evolution of modern clades of snakes such as boas (Booidea) is still based on isolated bones. Here, we resolve the phylogenetic relationships of Eoconstrictor fischeri comb. nov. and other booids from the early-middle Eocene of Messel (Germany), the best-known fossil snake assemblage yet discovered. Our combined analyses demonstrate an affinity of Eoconstrictor with Neotropical boas, thus entailing a South America-to-Europe dispersal event. Other booid species from Messel are related to different New World clades, reinforcing the cosmopolitan nature of the Messel booid fauna. Our analyses indicate that Eoconstrictor was a terrestrial, medium- to large-bodied snake that bore labial pit organs in the upper jaw, the earliest evidence that the visual system in snakes incorporated the infrared spectrum. Evaluation of the known palaeobiology of Eoconstrictor provides no evidence that pit organs played a role in the predator–prey relations of this stem boid. At the same time, the morphological diversity of Messel booids reflects the occupation of several terrestrial macrohabitats, and even in the earliest booid community the relation between pit organs and body size is similar to that seen in booids today.
Background: Patients with rare diseases (RDs) are often diagnosed too late or not at all. Clinical decision support systems (CDSSs) could support the diagnosis in RDs. The MIRACUM (Medical Informatics in Research and Medicine) consortium, which is one of four funded consortia in the German Medical Informatics Initiative, will develop a CDSS for RDs based on distributed clinical data from ten university hospitals. This qualitative study aims to investigate (1) the relevant organizational conditions for the operation of a CDSS for RDs when diagnose patients (e.g. the diagnosis workflow), (2) which data is necessary for decision support, and (3) the appropriate user group for such a CDSS.
Methods: Interviews were carried out with RDs experts. Participants were recruited from staff physicians at the Rare Disease Centers (RDCs) at the MIRACUM locations, which offer diagnosis and treatment of RDs.
An interview guide was developed with a category-guided deductive approach. The interviews were recorded on an audio device and then transcribed into written form. We continued data collection until all interviews were completed. Afterwards, data analysis was performed using Mayring’s qualitative content analysis approach.
Results: A total of seven experts were included in the study. The results show that medical center guides and physicians from RDC B-centers (with a focus on different RDs) are involved in the diagnostic process. Furthermore, interdisciplinary case discussions between physicians are conducted.
The experts explained that RDs exist which cannot be fully differentiated, but rather described only by their overall symptoms or findings: diagnosis is dependent on the disease or disease group. At the end of the diagnostic process, most centers prepare a summary of the patient case. Furthermore, the experts considered both physicians and experts from the B-centers to be potential users of a CDSS. The experts also have different experiences with CDSS for RDs.
Conclusions: This qualitative study is a first step towards establishing the requirements for the development of a CDSS for RDs. Further research is necessary to create solutions by also including the experts on RDs.
Background: Rare Diseases (RDs), which are defined as diseases affecting no more than 5 out of 10,000 people, are often severe, chronic and life-threatening. A main problem is the delay in diagnosing RDs. Clinical decision support systems (CDSSs) for RDs are software systems to support clinicians in the diagnosis of patients with RDs. Due to their clinical importance, we conducted a scoping review to determine which CDSSs are available to support the diagnosis of RDs patients, whether the CDSSs are available to be used by clinicians and which functionalities and data are used to provide decision support.
Methods: We searched PubMed for CDSSs in RDs published between December 16, 2008 and December 16, 2018. Only English articles, original peer reviewed journals and conference papers describing a clinical prototype or a routine use of CDSSs were included. For data charting, we used the data items “Objective and background of the publication/project”, “System or project name”, “Functionality”, “Type of clinical data”, “Rare Diseases covered”, “Development status”, “System availability”, “Data entry and integration”, “Last software update” and “Clinical usage”.
Results: The search identified 636 articles. After title and abstracting screening, as well as assessing the eligibility criteria for full-text screening, 22 articles describing 19 different CDSSs were identified. Three types of CDSSs were classified: “Analysis or comparison of genetic and phenotypic data,” “machine learning” and “information retrieval”. Twelve of nineteen CDSSs use phenotypic and genetic data, followed by clinical data, literature databases and patient questionnaires. Fourteen of nineteen CDSSs are fully developed systems and therefore publicly available. Data can be entered or uploaded manually in six CDSSs, whereas for four CDSSs no information for data integration was available. Only seven CDSSs allow further ways of data integration. thirteen CDSS do not provide information about clinical usage.
Conclusions: Different CDSS for various purposes are available, yet clinicians have to determine which is best for their patient. To allow a more precise usage, future research has to focus on CDSSs RDs data integration, clinical usage and updating clinical knowledge. It remains interesting which of the CDSSs will be used and maintained in the future.
According to the free radical theory of aging, reactive oxygen species (ROS) have been proposed to be a major cause of aging for a long time. Meanwhile, it became clear that ROS have diverse functions in a healthy organism. They act as second messengers, and as transient inhibitors of phosphatases and others. In fact, their detrimental role is highly dependent on the context of their production. NADPH oxidases (Nox) have been discovered as a controllable source of ROS. NoxO1 enables constitutive ROS formation by Nox1 by acting as a constitutively active cytosolic subunit of the complex. We previously found that both Nox1 and NoxO1 were highly expressed in the colon, and that NoxO1-/- deficiency reduces colon health. We hypothesized that a healthy colon potentially contributes to longevity and NoxO1 deficiency would reduce lifetime, at least in mouse. In contrast, here we provide evidence that the knockout of NoxO1 results in an elongated life expectancy of mice. No better endothelial function, nor an improved expression of genes related to longevity, such as Sirt1, were found, and therefore may not serve as an explanation for a longer life in NoxO1 deficiency. Rather minor systemic differences, such as lower body weight occur. As a potential reason for longer life, we suggest better DNA repair capacity in NoxO1 deficient mice. Although final fatal DNA damage appears similar between wildtype and NoxO1 knockout animals, we identified less intermediate DNA damage in colon cells of NoxO1-/- mice, while the number of cells with intact DNA is elevated in NoxO1-/- colons. We conclude that NoxO1 deficiency prolongs lifetime of mice, which correlates with less intermediate and potentially fixable DNA damage at least in colon cells.
Diese Dissertation soll die Frage beantworten, ob die Forderung der Krankenkassen, die Nabelhernie und die epigastrische Hernie als ambulante Operation zu realisieren, gerechtfertigt bzw. sinnvoll ist. Sie soll ferner Steuergrößen und Maßnahmen identifizieren, die die Überführung des Eingriffs in den ambulanten Rahmen begünstigen können.
Seit den achtziger Jahren des letzten Jahrhunderts wird versucht, durch die kurzstationäre und ambulante Operation verschiedener Krankheitsbilder der Forderung nach Kostenersparnis im Gesundheitswesen nachzukommen. Von den Krankenkassen wird gefordert, den Verschluss einer Hernia umbilicalis: Ohne Plastik: Mit Exstirpation einer Nabelzyste, den Verschluss einer Hernie epigastrica: Ohne Plastik sowie den Verschluss einer Hernia umbilicalis: Mit Plastik im Rahmen einer ambulanten Operation zu korrigieren. Entsprechend wurden diese Eingriffe 2005 in die Liste der ambulant zu erbringenden und stationsersetzenden Maßnahmen aufgenommen. Dennoch liegt die durchschnittliche stationäre Verweildauer nach diesem Eingriff weiterhin bei 3,5 Tagen.
Phylogenetisch ist die Entstehung von Nabelhernien durch anatomisch präformierte Schwachstellen der Bauchwand bedingt, an denen Muskulatur fehlt und nur Aponeurosen und Faszien vorhanden sind. Die Entstehung wird aber auch durch Begleiterkrankungen und Risikofaktoren begünstigt.
In die vorliegende Untersuchung wurden nach Anwendung verschiedener Ausschlusskriterien 95 Patienten aufgenommen, die im Zeitraum zwischen dem 24. August 2009 und dem 24. Juni 2012 mit der Hauptdiagnose einer Nabelhernie bzw. epigastrischen Hernie - Diagnose nach ICD10 - K42.0, K42.1, K42.9, K43.0, K43.1 und K43.9 in der Klinik für Allgemein- und Viszeralchirurgie der Hochtaunuskliniken Bad Homburg operiert wurden. Die selektierten Patienten, welche betrachtet wurden, teilten sich in 61 primäre Nabelhernien, fünf Rezidivnabelhernien, elf epigastrische Hernien, drei Rezidive epigastrischer Hernien und 15 Kombinationseingriffe mit simultaner Operation einer Nabelhernie und einer Leistenhernie auf.
Als Operationsverfahren kam entweder eine Naht Stoß-auf-Stoß (NSAS), die Technik nach Mayo mit einer Fasziendoppelung oder die Implantation von alloplastischem Fremdmaterial entweder mittels eines Ventralex™ Patch oder Proceed™ Patch in Sublay-Technik oder bei ausgedehnten Befunden eine retromuskuläre Mesh Plastik (RMMP) zum Einsatz. Als laparoskopisches Verfahren wurde das Intraperitoneale Onlay Mesh (IPOM) verwendet.
Die Auswertung für die deskriptive Statistik erfolgte mit Microsoft® Excel® 2013. Anschließend wurde die Auswertung der explorativen wie auch der mathematisch/induktiven Statistik mit Hilfe von BiAS. für Windows™ Version 11/2015 durchgeführt.
Nach Analyse des Patientengutes konnte anhand von Korrelationsanalysen herausgearbeitet werden, dass das Alter, die Anzahl der Begleiterkrankungen, die Anzahl der Risikofaktoren und die ASA-Klassifikation (American Society of Anesthesiologists), die Größe der Bruchlücke in Zentimetern und die Schmerzen am zweiten postoperativen Tag einen schwachen Zusammenhang rho (ρ) zwischen 0,23 und 0,39 mit der Liegedauer bei jedoch signifikanten p-Wert p ≤ 0,05 aufwiesen. Einen stärkeren Zusammenhang mit einem Korrelationskoeffizienten ρ von 0,42 und 0,40 im Hinblick auf die Liegedauer zeigten hierbei die Operationsdauer und die Schmerzen am ersten postoperativen Tag. Den stärksten signifikanten Zusammenhang mit einem ρ von 0,64 zeigten die Schmerzen am dritten postoperativen Tag.
Die Verweildauer wurde auch durch die Wahl des Operationsverfahrens beeinflusst. Hier ergab sich eine signifikante Verlängerung der Verweildauer durch unterschiedliche Operationsverfahren sowohl in der Begutachtung des Gesamtkollektivs als auch in der Subgruppe NSAS, Mayo und Patch.
Im Anschluss konnte anhand multivariater Analysen festgestellt werden, dass die Operationsdauer, das Operationsverfahren und die ASA-Klassifikation mit p-Werten ≤ 0,05 mit der Liegedauer signifikant korrelierten. Auch konnte mit Hilfe der multivariaten Analyse aufgezeigt werden, dass die Größe der Bruchlücke in Zentimetern und die Schmerzen am ersten und zweiten postoperativen Tag mit Signifikanzwerten ≤ 0,05 mit der Liegedauer korrelierten.
Nach der durchgeführten Analyse, wie auch nach Betrachtung der Literatur, ist die Grundlage zur Durchführbarkeit einer ambulanten Operation die Erfüllung der medizinischen Voraussetzungen, die Erfüllung der Kriterien für ambulante Operationen und die Erfüllung der Entlassungskriterien. Zudem sollten Patienten mit kardiovaskulären Erkrankungen, insbesondere bei Vorliegen einer Herzinsuffizienz, aber auch bei COPD, Asthma und Schlafapnoesyndrom und einem BMI größer 30 nicht für eine ambulante Operation in Betracht gezogen werden. Auch gelten ein ASA Status größer als 2, Nebenwirkungen der (Allgemein-)Narkose wie PONV, Schwindel, Schläfrigkeit und ein erhöhtes postoperatives Schmerzniveau sowie eine große Defektgröße als hinderlich für die ambulante Durchführung der Operationen.
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Die vorliegende Studie versucht einen Beitrag zur Erforschung von Implementationsmöglichkeiten des bilingualen Sprachvermögens von Schüler*innen mit Migrationshintergrund für den Regelschulkontext zu leisten, indem ein bilinguales Interaktionsangebot beim Peer-Learning für türkisch-deutschsprachig aufwachsende Schüler*innen der dritten und vierten Klasse in einem quasi-experimentellen Setting unter Verwendung von Mixed Methods untersucht wird.
Methoden
(2020)
Rezension zu: Akremi, Leila, Nina Baur, Hubert Knoblauch und Boris Traue (Hrsg.): Handbuch Interpretativ forschen. Weinheim, Basel: Beltz Juventa 2018. 961 Seiten. ISBN: 978-3-7799-3126-3. Preis: C 49,95.
This paper defends The Transformation of Values into Prices on the Basis of Random Systems, published in EIER, by answering to the Comments made in the same journal by Professors Mori, Morioka and Yamazaki. The clarifications mainly concern the justification of the randomness assumptions, the conditions needed to obtain the equality of total profit with total surplus value in the simplified one-industry system and the invariance of the results to changes in the units of measurement.
Background: Alterations in the SCN5A gene encoding the cardiac sodium channel Nav1.5 have been linked to a number of arrhythmia syndromes and diseases including long-QT syndrome (LQTS), Brugada syndrome (BrS) and dilative cardiomyopathy (DCM), which may predispose to fatal arrhythmias and sudden death. We identified the heterozygous variant c.316A > G, p.(Ser106Gly) in a 35-year-old patient with survived cardiac arrest. In the present study, we aimed to investigate the functional impact of the variant to clarify the medical relevance.
Methods: Mutant as well as wild type GFP tagged Nav1.5 channels were expressed in HEK293 cells. We performed functional characterization experiments using patch-clamp technique.
Results: Electrophysiological measurements indicated, that the detected missense variant alters Nav1.5 channel functionality leading to a gain-of-function effect. Cells expressing S106G channels show an increase in Nav1.5 current over the entire voltage window.
Conclusion: The results support the assumption that the detected sequence aberration alters Nav1.5 channel function and may predispose to cardiac arrhythmias and sudden cardiac death.
Monoterpenes and their monoterpenoid derivatives form a subclass of terpene(oid)s. They are widely used in medicines/pharmaceuticals, as flavor and fragrance compounds, or in agriculture and are also considered as future biofuels. However, for many of these substances, the extraction from natural sources poses challenges such as occurring at low concentrations in their raw material or because the natural sources are diminishing. Furthermore, many of the structurally more complex terpenoids cannot be chemically synthesized in an economic way. Therefore, microbial production provides an attractive alternative, taking advantage of the often distinct regio- and stereoselectivity of enzymatic reactions. However, monoterpenes and monoterpenoids are challenging products for industrial biotechnology processes due to their pronounced cytotoxicity, which complicates the production in microorganisms compared to longer-chain terpenes (sesquiterpenes, diterpenes, etc.).
The aim of this thesis was to generate a biotechnological complement to fossil-resources-based chemical processes for industrial monoterpenoid production. Therefore, a starting point for the further development of a microbial cell factory based on the microbe Pseudomonas putida KT2440 was aimed to be created. This production organism should be able to conduct a whole- cell biocatalysis to selectively oxyfunctionalize monoterpene hydrocarbons using renewable industrial by-products and waste streams as raw material for monoterpenoid production (Figure 1). As a model substance, the production of (-)-menthol should be addressed due to its industrial significance. (-)-Menthol is one of the world’s most widely-used flavor and fragrance compounds by volume as well as a medical component, having an annual production volume of over 30,000 tons. An approach for (-)-menthol production from renewable resources could be a biotechnological(-chemical) two-step conversion (Figure 1), starting from (+)-limonene, a by-product of the citrus fruit processing industry.
The thesis project was divided into three parts. In the first part, enzymes (limonene-3- hydroxylases) were to be identified that can convert (+)-limonene into the precursor of (-)-menthol, (+)-trans-isopiperitenol. To counteract product toxicity, in the second part, the tolerance of the intended production organism P. putida KT2440 towards monoterpenes and their monoterpenoid derivatives should be increased. Finally, in the third part, the identified hydroxylase enzymes would be expressed in the improved P. putida KT2440 strain to create a whole-cell biocatalyst for the first reaction step of a two-step (-)-menthol production, starting from (+)-limonene.
To achieve these objectives, different genetic/molecular biology and analytical methods were applied. In this way, two cytochrome P450 monooxygenase enzymes from the fungi Aureobasidium pullulans and Hormonema carpetanum could be identified and functionally expressed in Pichia pastoris, which can catalyze the intended hydroxylation reaction on (+) limonene with high stereo- and regioselectivity. A further characterization of the enzyme from A. pullulans showed that apart from (+) limonene the protein can also hydroxylate ( ) limonene, - and -pinene, as well as 3-carene.
Furthermore, within this thesis, mechanisms of microbial monoterpenoid resistance of P. putida could be identified. It was shown that the different monoterpenes and monoterpenoids tested have very different toxicity levels and that mainly the Ttg efflux pumps of P. putida GS1 are responsible for the tolerance to many of these compounds. Based on these results, a P. putida KT2440 strain with increased resistance to various monoterpenoids, including isopiperitenol, could then be generated, which can be used as a host organism for the further development of monoterpenoid-producing cell factories.
While within the scope of this work the heterologous expression of the fungal gene in prokaryotic cells in a functional form could not be realized despite different approaches, the identified enzymes, the monoterpenoid-tolerant P. putida strain and a plasmid developed for heterologous gene expression in P. putida provide a starting point for the further design of a microbial cell factory for biotechnological monoterpenoid production.
Degeneration of neurons, such as the inner ear spiral ganglion neurons (SGN), may be decelerated or even stopped by neurotrophic factor treatment, such as brain-derived neurotrophic factor (BDNF), as well as electrical stimulation (ES). In a clinical setting, drug treatment of the SGN could start directly during implantation of a cochlear implant, whereas electrical stimulation begins days to weeks later. The present study was conducted to determine the effects of consecutive BDNF and ES treatments on SGN density and electrical responsiveness. An electrode drug delivery device was implanted in guinea pigs 3 weeks after deafening and five experimental groups were established: two groups received intracochlear infusion of artificial perilymph (AP) or BDNF; two groups were treated with AP respectively BDNF in addition to ES (AP + ES, BDNF + ES); and one group received BDNF from the day of implantation until day 34 followed by ES (BDNF ⇨ ES). Electrically evoked auditory brainstem responses were recorded. After one month of treatment, the tissue was harvested and the SGN density was assessed. The results show that consecutive treatment with BDNF and ES was as successful as the simultaneous combined treatment in terms of enhanced SGN density compared to the untreated contralateral side but not in regard to the numbers of protected cells.