Journal articles on the topic 'Werner Siemens'

AbstractThis article revisits the interplay between enterprise, technology, science, and the state in the latter stages of Prussia's “early industrialization.” Tracing the footsteps of Werner Siemens as he sought to establish a business in Berlin during the 1840s, it highlights the social networks that enabled individuals and ideas to circulate between the military establishment, administrative departments, scientific circles, and entrepreneurial communities. At heart, these abstract entities constituted dense clusters of individuals who shared strong connections to one another, but whose contacts with other groups also enabled them to mobilize resources. During the 1840s, fostered by the dynamism of Berlin's expansion, social networks stepped into the breach caused by the Reform Era's upheaval of traditional employment structures and the emergence of a market economy. They provided a means of negotiating the uncertain socioeconomic circumstances that characterizedVormärzPrussia.

Seit Mitte der 1970er Jahre hat sich für die Musik von Manfred Trojahn, Wolfgang Rihm, Reinhard Febel, Hans-Jürgen von Bose, Wolfgang von Schweinitz und Detlev Müller-Siemens die Bezeichnung "Neue Einfachheit" als typologischer und historiographischer Terminus durchgesetzt. Durch die gemeinsamen Lehrer György Ligeti und Klaus Huber entwickelten die untereinander vielfach befreundeten Komponisten eine Art Gegenschule zur Darmstädter Schule. Im engeren Sinne schulbildend wirkten sie jedoch erst seit den 1980er Jahren als Lehrer der heute dreißig- bis vierzigjährigen Komponisten. Anhand der Musik von Matthias Pintscher wird die Frage diskutiert, inwiefern es sich bei der Musik dieser jüngeren Generation um eine Reformulierung von Ansätzen ihrer Lehrer aus den 1970er Jahren handelt. Ihr Verhältnis zur Musik der Tradition, insbesondere zu Gustav Mahler, zu tonalen Formen und musiksprachlichen Gesten, zu Hans Werner Henze und Helmut Lachenmann, sowie ihre Ablehnung der seriellen und postseriellen Avantgarde legt dies nahe. Angesprochen ist auch die Musik von Rebecca Saunders, Jörg Widmann, Johannes Maria Staud und anderen. Die exemplarische Erörterung des Begriffs einer "Zweiten Neuen Einfachheit" anhand von Pintschers "Fünf Orchesterstücken" (1997) versteht sich als ein erstes Diskussionsangebot über und mit dieser jüngeren Komponistengeneration.

Die Medizintechniksparte von Siemens steht mitten in einem rasanten Umbau. Im Mai als eigenständiges Tochterunternehmen ausgegliedert, richtet der neue CEO Bernd Montag den Medizintechnik-Riesen im Weltmarkt neu aus. Die hochprofitable Sparte soll flexibler und kundenorientierter werden.

Die hohen Anforderungen an moderne Fertigungssysteme erfordern leistungsfähige Engineering-Lösungen. Wie man die Identifikation von Fehlerursachen in komplexen Anlagen erleichtert, wurde in einer Machbarkeitsstudie des Fraunhofer IPK im Auftrag von Siemens DI FA untersucht. In der vorgestellten Lösung werden die Daten der Anlage auf Feldbusebene erfasst und in den digitalen Zwilling eingespeist. So kann das Verhalten der Komponenten taktgenau nachvollzogen werden. Dies elaubt einen tiefen Einblick in das System und unterstützt so bei der Fehlerbehebung.   Powerful engineering tools are required to keep modern production systems manageable. Siemens DI FA and the Fraunhofer IPK present a novel tool for root cause analysis within complex manufacturing systems. The solution combines a CAx plant model with control data recorded from the field bus. This creates a comprehensive digital twin, allowing to analyse past machine behavior with bus clock resolution.

Verkauft Cerner sein Deutschlandgeschäft? Kündigt das Unternehmen deutsche KIS ab oder werden sie nur marginal weiterentwickelt? Bereits vor über einem Jahr hat sich der US-Gigant Cerner die Health-IT von Siemens einverleibt – doch viele Ängste der Kliniken sind geblieben.

Am UK Aachen und an der Kaiserswerther Diakonie soll im Zuge der „IT-Schlüssel-Themen“ der Entscheiderfabrik eine Fallakten-App entwickelt werden, die behandlungsbeteiligten Medizinern und Pflegern Kommunizieren auf mobilen Endgeräten erlaubt. Weitere Akteure des Themas: mgm, Siemens, Authentidate International.

Zwischen CNC und Cloud: Mit „Sinumerik Edge“ von Siemens werden hochfrequente CNC-Massen- daten anhand von Softwareapplikationen direkt vor Ort erfasst, vorverarbeitet und analysiert. Die daraus generierten Maßnahmen verbessern die Produktivität von Maschinen und Linien, ohne deren CNCs zu belasten.

Wenige wettbewerbsrechtliche Problemstellungen haben in der letzten Zeit so viel Aufmerksamkeit auch außerhalb der Fachmedien hervorgerufen wie die Frage nach der Behandlung Chinas bzw. chinesischer Unternehmen unter den Regularien des Wettbewerbsrechts der Europäischen Union. Prominentestes Beispiel hierfür sind sicherlich die Rufe nach einer Reform der Europäischen Fusionskontrolle, die seit der Untersagung des Zusammenschlusses der Unternehmen Siemens und Alstom durch die Europäische Kommission zunehmend lauter geworden sind. Während hier die Berücksichtigung zunehmender Konkurrenz aus Fernost im Rahmen der Zusammenschlusskontrolle im Vordergrund steht, stellt insbesondere auch die wettbewerbsrechtliche Beurteilung von Tätigkeiten chinesischer Staatsunternehmen auf dem Binnenmarkt das Unionsrecht vor Herausforderungen. Der folgende Beitrag beschäftigt sich daher schwerpunktmäßig mit Zusammenschlüssen unter Beteiligung chinesischer Staatsunternehmen und deren Zulässigkeit nach dem Fusionskontrollrecht, bevor die aktuellen Bestrebungen zur Reform des europäischen Wettbewerbsrechts seit der Entscheidung der Kommission im Fall Siemens/Alstom präsentiert werden.

ZusammenfassungNuklearmedizin als Fachgebiet wird zunehmend wichtiger für die Therapieentscheidung verschiedener Krankheitsbilder. Neu entwickelte Tracer, die nicht nur diagnostisch, sondern auch therapeutisch wirksam sind, erfordern aufseiten der Gerätetechnik neue, innovative Lösungen. Die Kombination der bewährten Gammakamera-Technik mit hochgenauer dosissparender CT-Bildgebung ermöglicht die Darstellung funktionaler metabolischer Vorgänge zeitgleich mit anatomischen Informationen. In diesem Artikel werden die aktuellen Lösungen von Siemens Healthineers für die molekulare Bildgebung im Detail dargestellt.

MindSphere ist das cloudbasierte, offene IoT-Betriebssystem von Siemens. Es verbindet Produkte, Anlagen, Systeme und Maschinen und ermöglicht es so, die Fülle von Daten aus dem Internet der Dinge (IoT) mit umfangreichen Analysen zu nutzen. Als eine sichere, skalierbare End-to-End-Lösung für die Industrie sorgt MindSphere für die Konnektivität von Anlagen und liefert somit handlungsrelevante Geschäftserkenntnisse, die zur Steigerung der Produktivität und Effizienz im gesamten Unternehmen nutzbar gemacht werden können. MindSphere ist weltweit verfügbar.

Der Aufwand für den Aufbau eines monolitischen Manufacturing Operations Management (MOM) ist sehr hoch. Deswegen und aufgrund der Aquise der Low-Code-Plattform Mendix hat Siemens untersucht, ob sich eine MOM-Lösung auf Basis von App-Bausteinen entwickeln lässt. Gleichzeitig wurde untersucht, wie sich eine solche Lösung von einer herkömmlichen Entwicklung unterscheidet und wie sie eingesetzt werden muss, damit sie Mehrwert erzeugt. Es zeigt sich, dass deren Modularität eine schrittweise Digitalisierung in kleinen und mittelständischen Unternehmenseinheiten ermöglicht.

Cloud-Plattformen werden in der industriellen Anwendung immer relevanter. Sie dienen sowohl als Datenablage, nehmen jedoch zunehmend auch Modellierungs-, Strukturierungs- und Austauschaspekte, sowohl für Engineering- als auch für Live-Daten wahr. In diesem Beitrag wird eine praxisnahe Anwendung vorgestellt, mithilfe derer Ingenieure in der Lage sind, die stetig steigende Anzahl von Daten in der Cloud sinnvoll abzubilden. Vorlage bilden hierzu bestehende Strukturen in Planungs-(CAE) bzw. Engineering-Systemen der Automatisierungstechnik und des Anlagenbaus. Das hierfür entwickelte Werkzeug „VisualHierarchy Modeller“ wird durch die Autoren am Beispiel der Cloudplattform MindSphere der Siemens AG vorgestellt. Dabei werden im gesamten Beitrag Analogien zur klassischen Software- und Plattform-Entwicklung aufgezeigt, um die angewendeten Konzepte sinnvoll zu klassifizieren.

Ein Ring mit vielen Schlüsseln und eine umfangreiche Liste mit Passwörtern – Mitarbeiter, die in Industrieunternehmen Anlagen bedienen, müssen sich oft mit allerlei Sicherheitsmechanismen zum Anlagenschutz „herumschlagen“. Diese nicht unbedingt zeitgemäßen Lösungen sollen Anlagen vor unbefugtem Zugriff schützen. Aber weder mechanische Schlüssel noch Passwörter für das HMI (Human Maschine Interface) ermöglichen eine zuverlässige, einfache und praktikable Nachverfolgung der Bediener und Techniker. Zudem ist es problematisch, wenn Schlüssel verloren gehen oder Passwörter vergessen werden. Der sichere Maschinenzugriff stellt Anwender immer wieder vor Herausforderungen. Eine zuverlässige und pragmatische Lösung bietet der Sirius Act ID Key von Siemens.

Zusammenfassung Ziel: Unter Ausnutzung des kontinuierlichen Energiespektrums von Compton-gestreuten Photonen haben wir die untere Energieschwelle eines Positronen-Emissions-Tomographen (PET) bestimmt. Methode: In der PET werden bei der Datenakquisition Photonen erfaßt, deren Energie in dem Bereich liegt, der durch die untere und obere Schwelle des Energiediskriminators festgelegt ist. Um diese experimentell zu bestimmen, wird gewöhnlich die Energieantwort der Detektoren mit Gammastrahlern unterschiedlicher Energie gemessen, wobei man auf die Verfügbarkeit von Strahlern mit den gewünschten Energien angewiesen ist. Nutzt man hingegen das Energiespektrum von Compton-gestreuten Photonen, steht dafür auch eine kontinuierliche Energieverteilung zur Verfügung, die eine direkte Messung der Energieantwort der Detektoren erlaubt. Für die Messungen wurde eine aktivierte Cu-64-Punktquelle (ø = 1 mm) verwendet, die in eine Aluminiumkugel (ø = 2 cm) eingebracht wurde. Ergebnisse: Die von uns an dem Ganzkörperscanner ECAT EXACT HR+ (CTI/Siemens) gemessenen Werte für die untere Energieschwelle lagen systematisch unter den nominellen Werten und bestätigen damit die Resultate, die von C. Watson für Linienquellen gefunden wurden. Schlußfolgerung: Dies hat zur Folge, daß mehr niederenergetische Photonen gemessen werden als angenommen, was insbesondere bei der Streukorrektur berücksichtigt werden muß.

Fragestellung: Die chronische Subluxation des Nervus ulnaris aus dem Sulcus im Bereich des Ellbogens kann in seltenen Fällen Ursache unklarer chronischer Beschwerden an der Innenseite des Ellbogens sein. Methodik: Ein 30-jähriger Patient klagte über rezidivierende Schmerzzustände mit Kribbelparästhesien im Bereich des 4. und 5. Fingers unklarer Genese; ein 15-jähriger Knabe kam wegen eines tastbaren Strangs an der medialen Seite des Ellbogens ohne wesentliche Beschwerden in die Ambulanz. Die Untersuchung erfolgte mit einem hochfrequenten Linearschallkopf der Firma Siemens in Längs- und Querschnitt, ergänzt durch die dynamische Untersuchung. Ergebnisse: In beiden Fällen konnte der Nervus ulnaris in seinem gesamten Verlauf im Längs- und Querschnitt sicher identifiziert werden. Die Sonomorphologie und Echogenität sowie die Grösse des Nerven entsprach der gesunden Gegenseite. In beiden Fällen konnte die Subluxation des Nerven unter Flexion des Ellbogens über den Epicondylus medialis sonographisch nachgewiesen und dokumentiert werden. Schlussfolgerung: Die Sonographie ermöglicht bei der dynamischen Untersuchung eine Diagnose und Dokumentation einer Subluxation des Nervus ulnaris, wobei letztere bei der Indikationsstellung zur Operation zunehmend an Bedeutung gewinnt.

Abstract rFIX-Fc is an extended half-life (EHL) recombinant FIX concentrate approved for the prophylaxis and treatment of bleeding events in haemophilia B. A high laboratory and reagent-specific variability is described for rFIX-Fc activity measurements, overall in lower FIX concentrations. The aim of this single-center study was to evaluate the intra-laboratory variability of 17 different combinations coagulometers/reagents including both one stage clotting (OSC) and chromogenic assays with a focus on lower concentrations. Human FIX deficient plasma (FIX<1%, George King Bio-Medical) was spiked with rFIX-Fc at 150%, 100%, 80%, 20%, 5%, 2% and 1% based on label potency. We evaluated the spikes recovery with 3 coagulometers (STAR MAX (Stago), ACL TOP700 (Werfen) and Cs2100 (Siemens)) using for each instrument captive silica based aPTT reagents (PTT automate (Stago) and Pathromtin (Siemens)) and non-silica based (CK Prest (Stago), Synthafax (Werfen) and Actin FS (Siemens)). Two reagents (STA-Cephascreen (Stago) and Synthafax (Werfen)) were evaluated on all coagulometers because they potentially behave one the same way for EHL FIX products. The 2 available chromogenic assays (ROS FIXa (Rossix) and Biophen FIX:C were evaluated on all coagulometer. All experiments were performed by the same staff, in a single room, in triplicates with 3 dilutions. For a given combination, all the concentrations were evaluated on the same calibration curve. The spike recovery were calculated as the (mean of 3 experiments / targeted FIX value) x 100. The range values of 70% - 130% were considered as acceptable for spike recoveries'. The summary of all spikes recoveries' are presented in table 1. We confirmed that kaolin based OSC assays underestimate rFIX-Fc including for low concentrations. Acceptable recoveries were found for PTT automate on Stago coagulometer from 150% to 5% and an underestimation was found for low concentrations (2% and 1 %). Pathromtin and Actin FS performed on Cs2100 display acceptable recoveries on all the range of target values. Synthasil performed on ACL TOP700 have acceptable recoveries from 150% to 20% and an overestimation was found for low concentrations (5% to 1%). STA-Cephascreen performed on the 3 coagulometers has acceptable recoveries, except for low concentrations (5% to 1%) on ACL TOP coagulometer, leading to an overestimation of rFIX-FC measurements. Synthafax performed on the 3 coagulometers has acceptable recoveries with ACL TOP700 coagulometer for all the range of concentrations. This reagent adapted on STAR MAX coagulometer shows an overall overestimation of rFIX-Fc measurements (except for the 150% target concentration) and when adapted on a Cs2100 coagulometer, it displays acceptable recoveries except for low concentrations (5% to 1%) that are overestimated. The two chromogenic assays have acceptable recoveries for rFIX-Fc on all coagulometers from 150% to 50% concentrations. ROS FIXa underestimated rFIX-Fc recovery for the lower concentrations (1% and 2%) on STAR MAX and ACL TOP700 coagulometers. Biophen FIX:C underestimated rFIX-Fc recoveries for concentrations below 50% with all coagulometers. This study provides the pattern of several combinations coagulometers - reagents for rFIX-Fc measurements and confirms a high variability for several reagents for low concentrations. Table. Table. Disclosures Lebreton: Sobi: Consultancy, Research Funding.

Konventionelle akustische Hörgeräte bleiben trotz stetigen technischen Verbesserungen in ihrer Leistungsfähigkeit beschränkt. Aus physikalischen Gründen können damit Frequenzen über 5 kHz nicht oder nur sehr schwach übertragen werden. Der Hochfrequenzbereich ist aber für das Verstehen von Konsonanten entscheidend. Erst damit kann der Inhalt von Worten erfasst und verstanden werden. Im Weiteren ist das Problem der Lärmverstärkung durch akustische Hörgeräte nicht gelöst. Weitere Problemgebiete sind: hartnäckige Gehörgangsinfekte, Intoleranz für Ohrpassstücke, Feedbackpfeifen und Resonanzen beim Sprechen oder Singen. Implantierbare Hörgeräte wie die Soundbridge von Symphonix-Siemens und das MET von Otologics bieten neue Möglichkeiten der Hörverbesserung und der akustisch schöneren Versorgung. Seit der ersten Implantation einer Soundbridge im Jahr 1996 in der Schweiz profitieren seither weltweit fast tausend Patienten von diesem Quantensprung der Rehabilitation ihrer Schwerhörigkeit. Es handelt sich bei diesen Systemen um Teilimplantate. Ein externer Audioprozessor mit Mikrofon, Batterie, Computerchip und Sendeanlage wird mit Magnethaftung hinter dem Ohr im Haarbereich getragen. In der Regel werden vor einer Implantation zuerst die Möglichkeiten der konventionellen Hörgeräte ausgeschöpft. Im Erwerbsalter ist die Finanzierung in der Schweiz durch die IV gesichert. Im AHV-Alter werden die Kosten des externen Teils von der AHV übernommen. Für die Kosten der Implantation fragen wir die Krankenkassen an. In der Schweiz haben sich bisher erst einige wenige Otologen für dieses neue Gebiet interessiert. Die initial höheren Kosten eines Implantats werden durch die längere Lebensdauer von 20 bis 30 Jahren kompensiert. Konventionelle Hörgeräte müssen alle 5 bis 6 Jahre gewechselt werden. Wegen der qualitativen Verbesserung des Hörens und Verstehens wird die Zahl der Patienten mit implantierten Hörgeräten in den nächsten Jahren deutlich zunehmen. Weitere Implantatsysteme sind in klinischer Erprobung.

ZusammenfassungDeutsch für den Beruf ist nicht nur in Deutschland, im Kontext von Integration (DaZ für Berufszwecke), sondern auch im Ausland (im DaF-Bereich) ein hoch aktuelles und bildungspolitisch relevantes Thema. Dies gilt ganz besonders für China, wo das vor 35 Jahren eingeführte duale Ausbildungssystem boomt, in dessen Rahmen einige große deutsche Firmen als Ausbilder agieren (z. B. BMW, Daimler, Schleich, Siemens und andere). Selbstverständlich wächst in diesem Zusammenhang der Bedarf an geeigneten Unterrichtsmaterialien für Deutsch als Fach- und Berufsfremdsprache an Berufsschulen, Berufsfachschulen und für innerbetriebliche Weiterbildungen.Im vorliegenden Beitrag wird das von Studierenden des MA-Studiengangs „Interkulturelle Germanistik/DaF“ der Universität Göttingen in Zusammenarbeit mit dem Goethe-Institut Peking und dem Fachverband Deutsch als Fremd- und Zweitsprache e.V. entwickelte zweisprachige Lehrwerk DaF für die Automobilfertigung in China (A2–B1) vorgestellt, das in entsprechenden Ausbildungsgängen an chinesischen Berufsschulen oder bei firmeninternen Weiterbildungen eingesetzt werden kann und wird. Dabei werden folgende Aspekte beleuchtet: die Rahmenbedingungen und Durchführung des Projekts, das Konzept und die didaktischen Besonderheiten des Lehrwerks (Lehrwerkaufbau, Regionalisierung und Zielgruppenbestimmung, das Konzept der funktionalen Mehrsprachigkeit, der Szenariodidaktik und des interkulturellen Lernens in der Berufs- und Fachsprachenvermittlung) sowie dessen Nachhaltigkeit und generell die Adaptierbarkeit solcher kollaborativer Aktivitäten.

Zusammenfassung Das Ziel dieser Arbeit bestand in der Entwicklung eines langwelligen Strahlungsthermometers zur berührungslosen Messung von Oberflächentemperaturen in stationären Gasturbinen während des Betriebs der Turbinen innerhalb des EU-geförderten Projektes „Sensors Towards Advanced Monitoring and Control of Gas Turbine Engines (Acronym STARGATE)“. Im Rahmen der Arbeit wurden die infrarot-optischen Eigenschaften der Wärmedämmschichten und der vorhandenen Brenngase am ZAE Bayern bei hohen Temperaturen bis 1600 K und Drücken bis 13 bar bestimmt. Mit Hilfe dieser experimentellen Charakterisierungen konnte ein geeigneter Spektralbereich um 10 μm für das langwellige Strahlungsthermometer identifiziert werden. Entsprechend dieser Erkenntnisse wurde zunächst ein Laboraufbau mit geeigneten optischen Bauteilen (Filter, IR-Wellenleiter, etc.) realisiert und verifiziert. Anschließend wurde ein Prototyp für Messungen in Gasturbinen während des Betriebs der Turbinen entwickelt und in einem Turbinenteststand der Firma Siemens AG in Berlin erfolgreich getestet. Abschließend wurde eine Unsicherheitsanalyse durchgeführt, die eine erweiterte Messunsicherheit der gemessenen Temperaturen von etwa ± 30 K ergab.

Deutsches Historisches Museum (Hg.): Der Luthereffekt. 500 Jahre Protestantismus in der Welt Karl-Heinz Göttert: Luthers Bibel. Geschichte einer feindlichen Übernahme Werner Greiling, Holger Böning, Uwe Schirmer (Hg.): Luther als Vorkämpfer? Reformation, Volksaufklärung und Erinnerungskultur um 1800 Jakob Knab: Luther und die Deutschen (1517-2017) Marcel Nieden (Hg.): Ketzer, Held und Prediger. Martin Luther im Gedächtnis der Deutschen Andrew Pettegree: Die Marke Luther. Wie ein unbekannter Mönch eine deutsche Kleinstadt zum Zentrum der Druckindustrie und sich selbst zum berühmtesten Mann Europas machte – und die protestantische Reformation lostrat Alois Prinz: Wie aus Martin LUTHER wurde Hole Rößler (Hg.): Luthermania. Ansichten einer Kultfigur Lyndal Roper: Der Mensch Martin Luther. Die Biografie Heinz Schilling: 1517. Weltgeschichte eines Jahres Uwe Siemon-Netto: Luther – Lehrmeister des Widerstands Christopher Spehr, Michael Haspel, Wolfgang Holler (Hg.): Weimar und die Reformation. Luthers Obrigkeitslehre und ihre Wirkungen

Zusammenfassung Ziel: Mit rotierenden Stabquellen ist die zur Schwächungskorrektur der PET notwendige Transmissionsmessung auch nach Injektion der 18FDG technisch möglich (PIT). Die Arbeit untersucht die regionalen Schwächungskoeffizienten, Zählratendichten und relativen regionalen Uptake-Werte der PIT-korrigierten Myokard-PET verglichen mit der herkömmlichen Transmission vor der Radionuklidapplikation (RT), die mit einer Repositionierung des Patienten verbunden ist. Methodik: Ein Thorax-Phantom mit homogener Myokardfüllung, mit simulierten Myo- kard-Defekten und sechs Patienten mit fortgeschrittener koronarer Herzkrankheit und zurückliegenden Myokardinfarkten wurden in einem Tomographen ECAT Exact (Siemens CTI), bestückt mit drei rotierenden 68Ge/68Ga Stabquellen von je 120 MBq, untersucht. Die Transmissionsdaten (PIT, RT) einerseits und zum anderen die Emissionsdaten wurden unkorrigiert (Ε-UK) sowie schwächungskorrigiert mit der PIT (Ε-PIT) und der RT (E-RT) regional quantifiziert (lineare Schwächungskoeffizienten, Zählratendichten, standardisierte [SUV] und relative Speicherwerte bezogen auf das Maximum). Ergebnisse: Sowohl in den Phantomsimulationen als auch in den Patientenmessungen differierten die Schwächungskoeffizienten signifikant zwischen der PIT und RT. Im Vergleich zwischen Ε-PIT und E-RT konnten Auswirkungen auf die regionalen Speicherwerte nur bei myokardialen Aktivitätskonzentrationen größer als 10 kBq × ml−1 im Phantom gesichert werden. Die relativen Speicherwerte des simulierten Defektes im Phantom oder die SUV bzw. relativen Speicherwerte in den Patientenmessungen variierten nicht signifikant zwischen Ε-PIT und E-RT. Schlußfolgerung: Bei den für die klinische Myokard-PET eingesetzten FDG-Aktivitäten bis 300 MBq und einer Aktivität der Transmissionsquellen von je 120 MBq konnte eine relevante Beeinflussung der regionalen relativen Speicherwerte nicht nachgewiesen werden, wenn die Transmission nach der FDG-Appli- kation erfolgte.

Zusammenfassung Ziel der retrospektiven Studie war die Ermittlung der Prävalenz echter Thrombopenie und EDTA-induzierter Pseudothrombopenie bei Pferd und Pony sowie die Evaluation der diagnostischen und prognostischen Aussagekraft bei echter Thrombopenie. Material und Methoden: Bei 3592 internistischen Patienten (Jahre 2008-2015) wurde eine hämatologische Untersuchung (ADVIA® 2120, Siemens) durchgeführt. Einschlusskriterien waren eine Thrombozytenzahl von < 90 x 109/l (EDTABlut) bzw. < 84 x 109/l (Zitratblut). Es erfolgte eine Einteilung in echte, EDTA-induzierte und fragliche Thrombopenie. Probanden mit einer echten Thrombopenie wurden bezüglich des Vorstellungsgrundes in neun Gruppen sowie in vier Diagnosegruppen (Entzündung, Neoplasie, nichtentzündliche Darmerkrankung, sonstige Erkrankungen) eingeteilt. Die Häufigkeit der Diagnosen wurde mit derer der gesamten Patientenpopulation der Klinik verglichen. Ergebnisse: Bei 123/3592 Patienten (3,4 %) bestand eine Thrombopenie, wobei 60/123 (49 %) eine echte, 6/123 (5 %) eine EDTA-induzierte und 57/123 (46 %) eine fragliche Thrombopenie aufwiesen. Bei der Auswertung der echten Thrombopenien waren die häufigsten Vorstellungsgründe Mattigkeit (23/60, 38 %), Fieber (19/60, 32 %) und Kolik (17/60, 28 %). Von den betroffenen Pferden zeigten 25/60 (42 %) eine entzündliche Grunderkrankung, 11/60 (18 %) eine Neoplasie, 10/60 (17 %) eine nichtentzündliche Darmerkrankung und 14/60 (23 %) sonstige Erkrankungen. Im Vergleich mit der Gesamtpopulation der Klinik zeigte sich mit 18 % im Vergleich zu 1 % eine deutlich erhöhte Häufigkeit der Neoplasien. Die Mortalität lag mit 38 % signifikant höher als in der Gesamtpopulation. Auffallend war eine Mortalität von 32 % in der Gruppe der Entzündungen und von 82 % in der Gruppe der Neoplasien. Schlussfolgerung und klinische Relevanz: Eine echte Thrombopenie ist beim internistisch erkrankten Pferd nicht häufig zu beobachten und sollte durch eine Messung im Zitratblut gesichert werden. Eine Thrombopenie stellt selten den primären Vorstellungsgrund dar und muss bei Neoplasien und Entzündungen als negativer prognostischer Faktor betrachtet werden.

Abstract Es gibt sie – langfristige russische Direktinvestitionen in Deutschland, wie die von Ilim Timber. Ursprünglich wollte das St. Petersburger Forstprodukteunternehmen nur deutsche Maschinen für eine neue Produktionsstätte in Russland kaufen und entschied sich dann dazu, zwei komplette Sägewerke in Wismar und Landsberg zu übernehmen (Tepavcevic, 2013) – oder die des Investors und Vorsitzenden der Sankt Petersburger Kirov-Werke Georgi Semenenko in Rostock (Mangler, 2017). Sie dienen nicht – wie oftmals bei russischen Investitionen in Deutschland unterstellt – der Kapital- oder Systemflucht, sondern werden aus strategischen Überlegungen heraus präzise geplant und erweisen sich als ökonomisch nachhaltig. Und umgekehrt gibt es auch die deutschen Erfolgsgeschichten in Russland, wie die von Pobeda Knauf, von Siemens Gas Turbine Technologies – einem Gemeinschaftsunternehmen der Siemens AG und der russischen Power Machines zur Produktion von Gasturbinen –, der Robert Bosch GmbH, von Mustang Neva im Bereich der Textilherstellung oder der Beteiligung von Henkel an der ERA AG in Tosno, die Wasch-, Reinigungs- und Scheuermittel sowie Kosmetika herstellt. Aber das wirtschaftspolitische Umfeld wird rauer. Ein Indikator dafür sind neben den kurzfristig reagierenden Import- und Exportzahlen vor allem die auf Langfristigkeit und Verlässlichkeit fußenden Investitionen russischer Unternehmen in Deutschland sowie deutscher Unternehmen in Russland. Der „Russian Investment Monitor“ der Hochschule Stralsund sowie der „German Investment Monitor“ der Polytechnischen Hochschule „Peter der Große“ in Sankt Petersburg ermöglichen eine fundierte Analyse und dienen als zuverlässiges Barometer der deutsch-russischen Wirtschaftsbeziehungen. When analyzing the long-term trade relations between two countries, import and export data are of limited help. Here the direct investment behavior is a much better indicator. However, direct investment figures entirely based on the stocks of investment are open to interpretation and might be even misleading. This is where the “Russian Investment Monitor” in Germany and the “German Investment Monitor” in Russia is of help. Analyzing investment behavior on the company level reveals the trust investors assign to their home country and the host country. Russian investments in Germany seem to be declining with China taking over the lead. Moreover, the Russian investments in Germany seem to a large part be motivated by capital flight rather than by traditional investment motives. However, exceptions to the rule exist. On the other hand, German investments in the Russian Federation seem to be more strategic and economically sustainable although the challenging political environment has reduced the German investment activity in Russia and opened the door to increasing Chinese direct investments. In summary, the German-Russian investment relations seem to be at the crossroads. Keywords: quot doing business ranking quot, investitionsverhalten, investitionstätigkeit, effizienzerhöhung, direktinvestitionen

Background The thrombocytopenic purpura (TTP) is a life-threatening condition characterized by microvascular thrombosis where it is of great importance to shorten the time to the treatment. TTP can be caused by congenital or acquired deficiency of ADAMTS13 (an enzyme that cleaves the von Willebrand factor). Deficiency leads to the accumulation of ultra-large von Willebrand multimers, which causes platelet aggregation and the formation of microthrombi. TTP laboratory findings include thrombocytopenia, hemolytic anemia, the presence of schistocytes and a markedly reduced activity of ADAMTS13. ADAMTS13 activity can be analyzed using an ELISA method. We have evaluated whether a new semi-quantitative method, TECHNOSCREEN from Technoclone, can be used as a screening method to shorten the time for patient diagnosis. Method We analyzed 43 unidentified samples with known ADAMTS 13 activity, which consisted of 20 samples with an ADAMTS13 activity <10%. The new screening method (TECHNOSCREEN ADAMTS13 Activity) was compared to the existing ELISA method (TECHNOZYM ADAMTS13 Activity ELISA). Both methods were from Technoclone, Vienna, Austria. The methods are based on incubating patient plasma with von Willebrand fragments and specific antibodies to cleavage fragment. Color intensity correlates with the amount of cleavage and thus ADAMTS13 activity of the sample. In the screening method, color development takes place in a flow through test device and is semi-quantitatively graded by visual comparison against a color chart graded as 0.0, 0.1, 0.4 and 0.8 IU /mL. Results and conclusion The results showed good agreement between the existing ELISA and the newTECHNOSCREEN method. Sensitivity was 100% and specificity 71% if the ELISA is used as a gold standard. In May 2019, the TECHNOSCREEN method was introduced as a first-line analysis. This has resulted in faster patient diagnosis as well as saving laboratory staff time. The TECHNOSCREEN assay takes about 1 hour to perform compared to about 5 hours for the ELISA. To exactly quantify ADAMTS13 activity or detect the presence of antibodies, the ELISAs are performed approximately once a week. Disclosures Binder: Technoclone: Employment. Antovic:Shire: Other: Grants and Personal Fees; Roche: Other: Personal Fees; Stago: Other: Personal Fees; Werfen: Other: Personal Fees; Siemens: Other: Personal Fees; Sobi: Other: Personal Fees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees; CSL Behring: Other: Personal Fees.

Abstract Development of inhibitors to Factor VIII is a serious and not uncommon (occurs in about 30% of treated patients) complication of the treatment with factor concentrate in hemophilia A. Treatment of patients with inhibitors is complicated, expensive and not always successful. By-pass agents (rFVIIa and aPCC) have been considered as a treatment of choice for those patients. Very recently bispecific factor IXa- and factor X-directed antibody - Emicizumab has been approved for the treatment of hemophilia A patients with inhibitors. However, there are data from the clinical studies which raise concerns about potential prothrombotic effect of Emicizumab in combination with by-pass agents particularly aPCC. To elucidate a potential mechanism of hypercoagulability we have investigated fibrin clot quality in hemophilic plasma after addition of a sequence identical analogue (SIA) of Emicizumab in combination with by-pass agents. Parameters of fibrin clot turbidity (lag time, Max Abs, Slope, Slope time) were measured in recalcified FVIII-deficient plasma samples, after addition of low thrombin concentration (0.04 NIH/mL) and different concentrations of SIA (200 and 600 nM), rFVIIa (1.75 and 5.25 µg/mL) and aPCC (50 and 500 mU/mL). Pooled normal plasma (PNP) was used as control. After fixation, fibrin clots were analyzed by scanning electron microscopy (SEM) (Carl Zeiss, Oberkochen, Germany) and the thickness of individual fibers was measured using SIS iTEM software (FEI Company, Eindhoven, Netherlands). As previously determined, 50 randomly selected fibers in each sample were measured to obtain stable mean. All parameters of fibrin turbidity and structure were analyzed in triplicate and the results are presented as mean values. Fibrin clot in FVIII deficient plasma was difficult to analyze due to the lack of polymerization of fibrin monomers and absence of fiber formation. This structure is loose and prone to fibrinolysis. Interestingly the similar structure was observed after addition of both concentrations of rFVIIa while after addition of SIA fibrin structure improves. The best effect using single agent was noticed after addition of aPCC in concentration of 500 mU/mL. In combination with SIA (both concentrations of 200 nM and 600 nM) aPCC in concentrations of 500 mU/mL generated clots with highest density formed from very thin fibers and small intrinsic pores. These clots are even tighter than those formed from PNP samples. Parameters of fibrin turbidity obtained with higher concentrations of agents as well as representative SEM scans are presented on the Figure 1. Addition of SIA to by-pass agents additionally improved fibrin quality in FVIII deficient plasma. Combination of therapeutic concentrations of aPCC and SIA may produce clots even less porous than those in normal plasma. Figure 1. Figure 1. Disclosures Chaireti: Shire: Research Funding. Antovic:NovoNordisk: Membership on an entity's Board of Directors or advisory committees; Shire: Honoraria, Research Funding; Sobi: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Werfen: Honoraria; Stago: Honoraria; Siemens: Honoraria; Roche: Honoraria; Sysmex: Honoraria.

Introduction: The primary objective of the FEIBA Global Outcome study (FEIBA GO) is to describe the long-term, real-world effectiveness and safety of activated prothrombin complex concentrate (aPCC; Feiba®, Baxalta Inc, a Takeda company, Lexington, MA, USA) for preventing and managing bleeding in patients with congenital hemophilia A or B with inhibitors (PwHI) across different clinical settings. This interim >18-month analysis corresponds to the report of May 2019. Methods: FEIBA GO (EUPAS6691) is an ongoing post-authorization, prospective, observational, multicenter cohort study. Male PwHI diagnosed before study entry and prescribed treatment with aPCC will be followed over 4 years; treatment regimens are prescribed at the physician's discretion. Ethics approval and patient consent were obtained. Results: Enrollment was completed on December 31, 2017, with 53 PwHI from 27 sites in 11 countries (hemophilia A: n=52, hemophilia B: n=1; median [range] age at baseline: 18 [2-71] years). Total annualized bleeding rate (ABR) and annualized joint bleeding rate (AJBR) for all bleeds are shown in Table 1 for the 21 patients who received prophylaxis or on-demand aPCC and had >18 months of follow-up data. Of 15 patients who received aPCC prophylaxis, 4 (26.7%) and 7 (46.7%) reported ABRs of ≤3 and AJBRs of ≤3, respectively. All 53 enrolled patients were included in the safety analysis. During the >18 month analysis period, a total of 139 non-serious treatment-emergent adverse events (TEAEs) were reported in 29 of 53 patients (including 9 events in 3 patients probably related to treatment and 2 events in 1 patient possibly related), and 40 serious TEAEs were reported in 17 patients. One possibly related serious TEAE of acute myocardial posterior wall infarction with embolic right coronary artery occlusion was reported in a patient with a catheter port; outcome: recovered/resolved. No thrombotic microangiopathies were reported. Conclusions: This interim analysis of real-world data at >18 months' follow-up is consistent with experience and continues to validate the safety and effectiveness of aPCC. Long-term follow-up data over 4 years from FEIBA GO will provide further information on the real-world effectiveness and safety of aPCC as monotherapy. Disclosures Windyga: Rigel Pharmaceuticals: Honoraria, Research Funding; Werfen: Honoraria, Research Funding; Baxalta/Shire (a Takeda company): Honoraria, Research Funding; Ferring Pharmaceuticals: Honoraria, Research Funding; CSL Behring: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Alexion: Honoraria, Research Funding; Novo Nordisk: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Bayer: Honoraria, Research Funding; Octapharma: Honoraria, Research Funding; Alnylam: Honoraria, Research Funding; Siemens: Honoraria, Research Funding; Sobi: Honoraria, Research Funding. Holme:Sobi: Honoraria, Research Funding; Shire, a Takeda company: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; CSL Behring: Honoraria; Bayer: Honoraria, Research Funding; Octapharma: Research Funding; Novo Nordisk: Honoraria. Hermans:Shire, a Takeda company: Consultancy; Novo Nordisk: Consultancy. Cid:Novo Nordisk: Honoraria; Shire, a Takeda company: Honoraria. Chatterjee:Baxalta US Inc., a Takeda company: Employment, Equity Ownership. Jiang:Baxalta US Inc., a Takeda company: Employment, Equity Ownership. Cano-Garcia:Shire, a Takeda company: Employment, Equity Ownership. Escuriola:Octapharma: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Research Funding; Sobi: Consultancy, Honoraria, Research Funding; Kedrion: Consultancy, Honoraria, Research Funding; Novo Nordisk: Consultancy, Honoraria, Research Funding; Grifols: Consultancy, Honoraria, Research Funding; Biotest: Consultancy, Honoraria, Research Funding; Shire, a Takeda company: Consultancy, Honoraria, Research Funding; CSL Behring: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding.

Abstract Introduction: The severe or moderately severe deficiency of coagulation factor IX (FIX) in patients with hemophilia B causes frequent and potentially serious bleeding, whereby joint bleeding can be one of the more serious complications. Management of bleeding episodes (BE) involves on-demand or prophylaxis replacement therapy for FIX. This study evaluated the safety profile and efficacy of a recombinant FIX, nonacog gamma (BAX326, RIXUBIS®, Shire, Lexington, MA, USA), for treatment of bleeding in adults and children with severe (FIX level <1 IU/dL) or moderately severe (FIX level 1-2 IU/dL) hemophilia B. Methods: This phase 3, prospective, open-label, multicenter, continuation study (NCT01286779) comprised patients from a phase 1/3 pivotal study (NCT01174446), a phase 2/3 pediatric study (NCT01488994), and naïve patients aged 2-70 years at screening. Nonacog gamma treatment was administered at the discretion of the investigator. Patients who transferred from earlier studies received on-demand treatment or prophylaxis, while naïve patients received only prophylaxis. Prophylactic dosing was standard (SP; 40-60 IU/kg in patients ≥12 years of age or 40-80 IU/kg in patients <12 years of age, twice weekly), modified (MP; ≤100 IU/kg, as determined by the investigator), or tailored to the patient's pharmacokinetic profile (PK; ≤120 IU/kg). One dose (75 ± 5 IU/kg) was given at each of the study visits to assess incremental recovery of nonacog gamma over time. The primary outcome measure was the occurrence of adverse events (AE) and serious AEs (SAE), regarded as possibly or probably related to nonacog gamma. Secondary outcomes included additional safety, annualized bleeding rate (ABR), hemostatic efficacy rating at resolution of bleed, and number of infusions per bleeding episode. Results: The study enrolled 117 patients, from 40 sites in 16 countries, of which 115 patients (74 patients with severe hemophilia, and 41 patients with moderately severe hemophilia) received treatment with nonacog gamma. All patients were male, with 21 patients <12 years of age and 94 patients ≥12 years of age.These included 65 patients from the phase 1/3 pivotal study, 20 patients from the phase 2/3 pediatric study and 30 naïve patients. Of 115 patients included in the full ananlysis set, 110 were treated with a prophylaxis regimen (SP, 108 patients; MP, 26 patients; PK, 3 patients ) and 13 patients received nonacog gamma on demand. Patients could switch between treatment regimens and may therefore be included in more than one regimen. A total of 459 AEs were reported in 85 (73.9%) patients; 443 nonserious AEs in 85 patients and 16 SAEs in 9 patients. The most commonly reported AEs included: nasopharyngitis (55 in 25 patients), arthralgia (48 in 15 patients), and pyrexia (23 in 14 patients). Only 2 nonserious AEs (positive antibody (Ab) tests to rFurin) in 2 patients, were considered nonacog gamma-related. These tests were negative by the time of study completion and considered transient. None of the SAEs were deemed related to nonacog gamma. No patients developed Abs to FIX, there were no thrombotic events or severe allergic reactions during or after treatment, and no significant treatment-related changes in vital signs. Clinical efficacy of nonacog gamma was rated as excellent or good in 991 (89%) of 1112 BEs. For all BEs, a mean (± SD) number of 1.8 (± 1.65) infusions were required until bleed resolution (Table 1). For on-demand treatment, the median ABR was 16.5 (n=13), whereas for overall prophylaxis the median ABR was 1.3 (n=108) (Table 2). Disclosures Windyga: Alnylam, Baxalta, Bayer, Novo Nordisk, Octapharma, Rigel Pharmaceuticals, Roche, Sanofi, Shire, SOBI: Research Funding; Alexion, Baxalta, Bayer, CSL Behring, Ferring Pharmaceuticals, Novo Nordisk, Octapharma, Rigel Pharmaceuticals, Roche, Sanofi, Shire, Siemens, SOBI, Werfen: Membership on an entity's Board of Directors or advisory committees. Stasyshyn:CSL Behring, Novonordisk, Shire: Honoraria; Novonordisk, Pfiser , Shire: Speakers Bureau. Engl:Shire: Employment, Equity Ownership. Tangada:Shire: Employment, Equity Ownership.

Abstract Background Hemophilia A with or without inhibitors to factor VIII (FVIII) has a major impact on the quality of life of people with this condition. This may be exacerbated by the treatment burden associated with current factor treatments that require frequent IV administration to reduce the risk of bleeding. Previous studies have noted that patients favor treatments that have a goal of achieving a "normal life" and avoid negative effects (e.g. infusion-related pain, time-consuming, or high treatment burden) (Cimino et al. Patient Prefer Adherence 2014). Two Phase III studies recently demonstrated the efficacy and safety of subcutaneous emicizumab administered weekly (QW) or every 2 weeks (Q2W) in persons with hemophilia A (PwHA) without inhibitors (HAVEN 3; NCT02847637; Mahlangu et al. N Engl J Med 2018, in press), and every 4 weeks (Q4W) in PwHA with or without inhibitors (HAVEN 4; NCT03020160; Pipe et al. WFH 2018). The studies included questionnaires developed and validated to investigate patients' preference and satisfaction with emicizumab compared with prior treatment. Methods In HAVEN 3, PwHA without inhibitors aged ≥12 years on prior episodic FVIII were randomized 2:2:1 to receive emicizumab QW (Arm A), Q2W (Arm B), or to no prophylaxis control (Arm C). Patients on prior prophylactic FVIII received emicizumab QW (Arm D). In HAVEN 4, PwHA with or without inhibitors aged ≥12 years with prior episodic bypassing agents (BPAs) or prophylactic FVIII received emicizumab Q4W. Patient preference was assessed through the Emicizumab Preference Survey (EmiPref) at Week 17 in both studies when patients had gained sufficient experience with emicizumab, potential bias due to anticipation associated with being in a study subsided, and they could still reliably recall their experience with prior therapy. The survey included three questions: patients were initially asked which they preferred - previous hemophilia treatment, new study treatment, or no preference. Those expressing a preference were then asked to rank the top three reasons for their choice. Finally, patients could provide additional free text related to their experience with emicizumab. Treatment satisfaction was assessed in Arm D of HAVEN 3 using the Satisfaction Questionnaire - Intravenous Subcutaneous Hemophilia Injection (SQ-ISHI). This 16-item questionnaire was to be completed at baseline and then either Week 21 or 25 after initiation of emicizumab. Results EmiPref was completed by 95/134 patients (71%) from Arms A, B, or D in HAVEN 3. Eighty-nine patients (94%) preferred emicizumab to their previous treatment and only 2 (2%) favored their previous treatment. The most frequent reasons selected for preference included a more convenient mode of administration ("frequency of treatments was lower" and "route of administration was easier") and reduced concern of bleeds ("worries about having bleeds were less"), reflecting the superior efficacy demonstrated in this study. In HAVEN 4, all 41 (100%) participants completed the EmiPref survey and all (100%) reported preferring emicizumab to their prior treatment. The most frequent reasons selected for preference were "the frequency of treatments was lower", followed by "the route of administration was easier", and "quality of life, in general, was better". When patients in HAVEN 3 and 4 were examined together, 99% (75/76) of patients who received prior FVIII or BPA prophylaxis favored emicizumab. Of the patients receiving prior episodic treatment, 92% (55/60) preferred emicizumab. Notably, all participants in HAVEN 3 and 4 continue to receive emicizumab beyond the primary analysis, including those who did not report favoring emicizumab, confirming the preference for emicizumab. The results of the SQ-ISHI completed by 50 patients in Arm D of HAVEN 3 at Week 21 indicated that 90% of patients were "much more" or "a lot more satisfied" with their current emicizumab prophylaxis compared with their pre-study treatment. Conclusions Almost all patients in HAVEN 3 and all patients in HAVEN 4 preferred emicizumab to their prior treatment. These results likely reflect the high efficacy and lower treatment burden previously reported. Such strong preference will be important for individuals currently receiving either episodic or prophylactic treatment when considering emicizumab prophylaxis in the future and may be associated with improved adherence, a substantial clinical obstacle with FVIII or BPAs. Disclosures Jimenez-Yuste: Roche: Consultancy, Research Funding; Shire: Consultancy, Research Funding; Bayer: Consultancy, Research Funding; Sobi: Consultancy, Research Funding; Octapharma: Consultancy, Research Funding; CSL Behring: Consultancy; Grifols: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; NovoNordisk: Consultancy, Research Funding. Shima:F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees; Chugai Pharmaceutical Co., Ltd: Consultancy, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: Anti-FIXa/X bispecific antibodies , Research Funding, Speakers Bureau. Paz-Priel:Genentech Inc: Employment. Parnes:Genentech Inc: Research Funding; Biogen Idec: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding; Shire: Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees; Shire: Membership on an entity's Board of Directors or advisory committees. Lehle:F. Hoffmann-La Roche: Employment. Giermasz:Bioverative, Biomarin, Genentech, Spark, Opko: Research Funding; Bioverativ, Biomarin, Genentech, Alexion, Bayer: Membership on an entity's Board of Directors or advisory committees. Campinha-Bacote:Genentech Inc: Employment. Niggli:F. Hoffmann-La Roche: Employment. Windyga:Alexion, Baxalta, Bayer, CSL Behring, Ferring Pharmaceuticals, Novo Nordisk, Octapharma, Rigel Pharmaceuticals, Roche, Sanofi, Shire, Siemens, SOBI, Werfen: Membership on an entity's Board of Directors or advisory committees; Alnylam, Baxalta, Bayer, Novo Nordisk, Octapharma, Rigel Pharmaceuticals, Roche, Sanofi, Shire, SOBI: Research Funding. Chebon:F. Hoffmann-La Roche: Employment. Trask:F. Hoffmann-La Roche: Employment; Genentech Inc: Employment. Mahlangu:Alnylam: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy; Bayer: Research Funding; Biogen: Research Funding, Speakers Bureau; Biomarin: Research Funding, Speakers Bureau; Catalyst Biosciences: Consultancy, Research Funding; Chugai: Consultancy; CSL Behring: Consultancy, Research Funding, Speakers Bureau; NovoNordisk: Consultancy, Research Funding, Speakers Bureau; LFB: Consultancy; Roche: Consultancy, Research Funding, Speakers Bureau; Sanofi: Research Funding, Speakers Bureau; Shire: Consultancy, Research Funding, Speakers Bureau; Sobi: Research Funding, Speakers Bureau; Spark: Consultancy, Research Funding. Pipe:Apcintex: Consultancy; Catalyst Biosciences: Consultancy; Genentech: Consultancy; Spark Therapeutics: Consultancy; Pfizer: Consultancy; CSL Behring: Consultancy; Bioverativ: Consultancy; R2 Diagnostics: Research Funding; HEMA Biologics: Consultancy; F. Hoffmann-La Roche Ltd: Consultancy; Ainylam: Consultancy; Freeline: Consultancy; Bayer: Consultancy; uniQure: Consultancy; Biomarin: Consultancy; Nove Nordisk: Consultancy; Shire: Consultancy, Research Funding; Siemens: Research Funding. Oldenburg:Grifols: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Chugai: Honoraria, Membership on an entity's Board of Directors or advisory committees; Biogen Idec: Honoraria, Membership on an entity's Board of Directors or advisory committees; Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL Behring: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biotest: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Swedish Orphan Biovitrum: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Background: Abnormalities of laboratory coagulation tests are common in cancer patients, underlying a subclinical hypercoagulable state. Due to the reciprocal interaction between coagulation and cancer, the biomarkers of hemostatic system activation are under evaluation as a tool for predicting cancer outcomes, disease progression, and mortality. Aim: In this analysis of a prospective cohort of patients with newly diagnosed metastatic gastro-intestinal (GI) cancer, we wanted to evaluate whether the pre-chemotherapy abnormalities of hemostatic biomarkers may predict for early-disease progression (E-DP), i.e. within 6 months from cancer diagnosis, and for 1-year overall survival (1-year OS). Methods: The study cohort included 304 newly diagnosed metastatic GI cancer patients, candidate to chemotherapy associated or not with immunotherapy, enrolled from March 2012 to March 2019 in the HYPERCAN study (ClinicalTrials.gov, ID# NCT02622815), an ongoing Italian prospective, multicenter, observational study; 191 healthy subjects acted as a control group. At diagnosis, before starting any curative chemotherapy, plasma samples were collected and tested for the following hypercoagulation biomarkers: D-dimer and fibrinogen by an automated coagulometer analyzer (ACL TOP500, Werfen Group), and prothrombin fragment 1+2 (F1+2) by ELISA (Siemens). In addition, thrombin generation (TG) potential was evaluated by Calibrated Automated Thrombogram (CAT) assay at 5 pM tissue factor and endogenous thrombin potential (TG ETP) and TG peak were analyzed. Clinical data [i.e. age, sex, BMI, ECOG Performance Status (ECOG-PS), relevant comorbidies] and the hemochromocytometric parameters were recorded at enrollment, whereas E-DP was clinically monitored every 3 chemotherapy cycles and during follow-up. Results: A cohort of 304 (205M/99F) metastatic GI cancer patients (206 colorectal and 98 gastric cancers) with a median age of 66 years (min-max: 29-85) was available for analysis. At enrollment, patients presented with a hypercoagulable state, as shown by significantly higher (p&lt;0.001) plasma levels of D-dimer, fibrinogen and F1+2, and significantly higher (p&lt;0.01) TG peak and TG ETP values than controls. After 6 months from the start of chemotherapy, E-DP had occurred in 80 patients, providing a cumulative incidence of 29.6% (CI 95% 24.1-35.1). E-DP subjects had significantly (p&lt;0.05) higher baseline D-dimer levels and TG ETP value than non-E-DP patients. Correlation analyses showed that pre-chemotherapy fibrinogen (β = -0.127; p=0.048), D-dimer (β = -0.198; p=0.002) and TG ETP (β = -0.133; p=0.034) levels were significantly and inversely associated with time to E-DP. By Multivariate Cox regression analysis, gastric cancer diagnosis (HR=1.546), pre-chemotherapy D-dimer (HR=1.001) and TG ETP values (HR=1.001) were identified as independent risk factors for E-DP. After 1 year from the start of chemotherapy, 228 patients were dead and the OS was 66.6% (CI 95% 61.3-71.9). Patients who died within 1 year showed higher baseline D-dimer, F1+2, fibrinogen, TG peak and TG ETP values compared to the remaining subjects. Multivariate Cox regression identified independent risk factors for 1-year OS the followings: gastric cancer diagnosis (HR=2.237), D-Dimer (HR=1.001) and TG ETP (HR=1.001) levels, white blood cell count (HR=1.094), ECOG-PS&gt;1 (HR=3.858), and chemotherapy plus immunotherapy treatment (HR=2.274). Conclusion: Our results show that, in newly diagnosed metastatic gastrointestinal cancer patients, before the start of antitumor treatment, a procoagulant state exists. Among the different hemostatic parameters evaluated, D-dimer and TG ETP appear as candidate biomarkers to predict for 6-month DP and 1-year OS. In particular, in this setting, the role of TG as a prognostic biomarker emerges for the first time in a large prospective cohort of GI cancer patients. Project funded by "5xMILLE" n. 12237 grant from the "Italian Association for Cancer Research (AIRC)" Disclosures Santoro: Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy; Arqule, Sanofi: Consultancy; Takeda, Roche, Abbvie, Amgen, Celgene, AstraZeneca, ArQule, Lilly, Sandoz, Novartis, Bristol-Myers Squibb, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD: Speakers Bureau; Takeda, Roche, Abbvie, Amgen, Celgene, AstraZeneca, ArQule, Lilly, Sandoz, Novartis, Bristol-Myers Squibb, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD: Speakers Bureau; Bristol Myers Squibb, Servier, Gilead, Pfizer, Eisai, Bayer, MSD: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy, Speakers Bureau; Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy.

Introduction: In Poland, the principles for the management of rare bleeding disorders as well as financing of medication are regulated by the National Program for the Management of Haemophilia and Related Bleeding Disorders. One objective of the Program for 2012-2018 was to include the financing of ITI for all haemophilia patients with inhibitor. The qualification for ITI was performed by a physician from a Haemophilia Treatment Centre (HTC). Goal: the aim of the study is/was prospective assessment of the efficacy of ITI in real life setting. Patients and Methods: The study comprised 30 patients with severe and one with moderate HA and HT FVIII inhibitors. Factor VIII activity (FVIII:C) was measured by one-stage clotting assay and Factor VIII inhibitors by a modified Nijmegen-Bethesda assay and expressed in Bethesda Units/ml (BU/ml). Cut-off level for positive inhibitor was ≥0.5BU/ml. The following data was collected: historical peak inhibitor titre (HPT), pre-ITI titre (measured 1 month prior to ITI), peak titre recorded during the course of ITI, time between inhibitor detection and ITI start, and ITI duration. During ITI course blood samples were collected every 4 weeks. Treatment regimen with dosing and type of FVIII concentrate was at the discretion of the physician in each HTC. ITI success was defined as inhibitor titre below 0.5 BU/ml with FVIII half-life ≥6h and FVIII recovery ≥66% of normal. Partial response to ITI was defined as clinical response to FVIII therapy with no anamnestic response despite the presence of FVIII inhibitor or FVIII half-life <6h and FVIII recovery <66% of normal. Results: 31 patients with HA and inhibitor were divided into two groups: Group 1 comprised 12 adults with severe HA, median age 36 years (mean 40.1±15.1 and Group 2 included 19 boys, (<18 years) (18 with severe, one with moderate HA), median age 8 years (mean 8.1±4.3) The median (mean) duration time between inhibitor detection and ITI start was 108 months (102±91) in Group 1 and 10 months (9±10) in Group 2. The median (mean) HPT before ITI was 68 BU/ml (156±193) and 50 BU/ml (126±242) in Group 1 and 2, respectively. ITI is still ongoing in one patient (Group 1) and in 3 boys (Group 2); these 4 patients were excluded from outcome analysis. Two adult patients (16,6%) of Group 1 and 2 boys (10,5%) of group 2 discontinued ITI therapy for a variety of reasons such as death (one patient), poor compliance or loss to follow-up; those patients were however included in the outcome analysis. The median (mean) duration of ITI was 24 months (30.8±31.7) (1-120) in Group 1 and 28 months (33.4±21.4) (6-84) in Group 2. The median (mean) peak titre during ITI was 40 BU/ml (225.7±185.7) in Group 1 and 85 (160±171.7) in Group 2. Immune tolerance to FVIII (success) was achieved in 3/11 adult (27.3%) and in 6/16 paediatric patients (37.5%). Median HPT, median time between inhibitor detection and ITI start, median peak inhibitor titre during ITI and median duration of ITI in patients who achieved immune tolerance were 380 BU/ml, 120 months, 8 BU/ml, 33 months in Group 1 and 22.5 BU/ml, 9.5 months, 205 BU/ml, 25 months in Group 2, respectively. No partial response to ITI was observed in our patients. The most common initial ITI regimen in both groups was 100 IU/kg/d of FVIII (50 - 200 IU/kg/d). In 28/31 (90.3%) patients only plasma derived FVIII concentrates were used which contained various amounts of von Willebrand factor. In two patients recombinant FVIII was administered. Recombinant, plasma derived and EHL FVIII concentrates were used in the case of one boy. In two patients immunosuppressive therapy (prednisone or rituximab) was concomitantly applied. Conclusions: it is our belief that the presented real-life data reflects i) the challenge of ITI therapy in clinical practice and ii) wide variety of approaches to ITI strategy in individual haemophilia treatment centres. Disclosures Windyga: Octapharma: Honoraria, Research Funding; Rigel Pharmaceuticals: Honoraria, Research Funding; Ferring Pharmaceuticals: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Alnylam: Honoraria, Research Funding; Alexion: Honoraria, Research Funding; Werfen: Honoraria, Research Funding; Novo Nordisk: Honoraria, Research Funding; Bayer: Honoraria, Research Funding; CSL Behring: Honoraria, Research Funding; Baxalta/Shire (a Takeda company): Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Siemens: Honoraria, Research Funding; Sobi: Honoraria, Research Funding.

Background: Etranacogene dezaparvovec is an investigational gene therapy for hemophilia B (HB) comprising an adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human factor IX (FIX) gene with a liver specific promoter. In a Phase 2b study, a single dose of etranacogene dezaparvovec provided mean FIX activity of 41.0% sustained at 1yr post-dose in 3 participants (pts). Although most gene therapy clinical studies exclude pts with pre-existing neutralizing antibodies (NAbs) to the capsid serotype, early clinical studies and nonhuman primate data suggest that generally prevalent titers of anti-AAV5 NAbs may not preclude successful transduction with etranacogene dezaparvovec. Aims: A Phase 3, Health Outcomes with Padua gene; Evaluation in Hemophilia B (HOPE-B; NCT03569891) was established to further assess efficacy and safety of etranacogene dezaparvovec in adults with HB with a wide range of pre-existing NAbs to AAV5. Here we report outcomes at 26 weeks (wks). Methods: HOPE-B is a Phase 3, open-label, single-dose, single-arm, multi-national trial in adult males with severe or moderate-severe HB (FIX≤2%). All pts received routine FIX prophylaxis prior to study. Pts were not excluded based on pre-existing NAbs to AAV5. Pts entered a prospective lead-in period of at least 6 months during which bleeding/factor use was monitored, then received a single intravenous dose of etranacogene dezaparvovec (2x1013 gc/kg). Pts will be followed for 5yrs. Primary endpoints comprised FIX activity (one stage) at 26 and 52wks after dosing and 52wk annualized bleeding rate. For pts with no clean post-treatment FIX samples (≥10d post exogenous FIX), factor activity was imputed as baseline value based on historic disease severity. Secondary endpoints include factor replacement use, adverse events (AEs), and reactive use of corticosteroids. Results: 75 pts were screened, of whom 67 entered lead-in. 54 pts were dosed (44 severe, 10 moderately severe HB) and completed 26wks of follow-up. Mean age (±SD) was 41.5 (15.8) yrs. 38/54 pts (70.4%) had bleeds (n=123) during the lead-in despite prophylaxis, and 23/54 (42.6%) had NAbs to AAV5 at baseline (max titer: 3212.3). Following treatment, FIX activity increased rapidly to a mean (SD; min,max) of 37.2% (±19.6; 1.0, 97.1) at wk26, representing a mean (SD; min,max) change from baseline of 36.0% (±19.7; 0, 96.1 p&lt;0.0001, confirmed by per-protocol sensitivity analysis). No correlation of pre-existing NAbs with FIX activity was identified up to a titer of 678.2; n=52, R2 = 0.078); a single pt had a NAb titer of 3212.3 and did not respond. In addition to this pt, one other pt received a partial dose and remained on prophylaxis; all other pts (96.3%) successfully discontinued routine prophylaxis. 39/54 (72.2%) pts reported 0 bleeds in the first 26wks post-treatment; 15 pts reported a total of 21 bleeds. Mean (SD) annualized FIX consumption (IU/yr/pt) was 292,304 (±171,079) during lead-in, decreasing to 12,622 (±36,466) at wk26 (96.0% reduction, N=54). Overall, 37/54 (68.5%) pts had any treatment-related AE post-treatment, the majority of which were mild (81.5%). No deaths occurred and no treatment-related SAEs were reported. 7 pts had infusion-related reactions; the infusion was discontinued in 1 pt. Treatment-related elevations in liver enzymes were reported in 9 pts and received steroids per protocol. All discontinued steroid use prior to wk26 and FIX activity was preserved in the mild range. In addition to these, the most frequent treatment-related AEs were headache (13.0%) and influenza-like illness (13.0%). No inhibitors to FIX were reported. No relationship between safety and NAbs was observed. Conclusions: The first co-primary endpoint of this study was met. This is the first report of a Phase 3 study in HB and the largest gene therapy trial cohort to date. Following a single dose of etranacogene dezaparvovec, FIX activity increased, without the need for prophylactic immunosuppression, into the mild-to-normal range at 26wks in pts with severe/moderately severe HB. Importantly, this included pts with titers of pre-existing anti-AAV5 NAbs. Pts were able to discontinue prophylaxis and bleeding was abolished in the majority. The safety profile was consistent with early phase AAV5 studies and together these data support a favorable safety and efficacy profile for etranacogene dezaparvovec Disclosures Pipe: HEMA Biologics: Consultancy, Other; Catalyst Biosciences: Consultancy; CSL Behring: Consultancy; ApcinteX: Consultancy; Bayer: Consultancy, Other: Contracted Research; BioMarin: Consultancy, Other: Contracted Research; Takeda: Consultancy; uniQure: Consultancy, Other; Siemens: Other; Pfizer: Consultancy; Freeline Therapeutics: Consultancy, Other: Contracted Research; Novo Nordisk: Consultancy, Other: Contracted Research; Roche/Genentech: Consultancy, Other: Contracted Research; Sangamo Therapeutics: Consultancy; Sanofi Genzyme: Consultancy, Other; Spark Therapeutics: Consultancy. Recht:CSL Behring: Consultancy, Other: personal fees; Genentech: Consultancy, Other: personal fees, Research Funding; Pfizer: Consultancy, Other: personal fees, Research Funding; BioMarin: Research Funding; Takeda: Consultancy, Other: personal fees, Research Funding; uniQure: Consultancy, Other: personal fees, Research Funding; Novo Nordisk: Consultancy, Other: personal fees, Research Funding; Spark: Research Funding; Bayer: Research Funding; Grifols: Research Funding; Hema Biologics: Consultancy, Research Funding; LFB: Research Funding; Octapharma: Research Funding; Catalyst Biosciences: Consultancy; Kedrion: Consultancy; Sanofi: Consultancy, Research Funding. Key:Uniqure: Consultancy; Grifols: Research Funding; Takeda: Research Funding; Novo Nordisk: Other: Chair of Grants Committee. Leebeek:Shire/Takeda: Research Funding; uniQure: Consultancy; Shire/Takeda: Consultancy; BioMarin: Consultancy; SOBI: Other: Travel grant; Roche: Other: DSMB member for a study; CSL Behring: Research Funding. Castaman:Bayer, Roche, Sobi, Grifols, Novo Nordick, Werfen, Kedrion: Consultancy, Honoraria, Speakers Bureau; CSL Behring, Pfizer, Sobi: Research Funding; Ablynx, Alexion, Bayer, Takeda, CSL Behring, Novo Nordisk, Pfizer, Roche,Sanofi, SOBI, uniQure: Membership on an entity's Board of Directors or advisory committees. Lattimore:uniQure: Other: Study Steering Committee member. Van Der Valk:Baxalta: Research Funding. Peerlinck:Bayer: Consultancy, Research Funding; CSL Behring: Consultancy, Research Funding; NovoNordisk: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Roche: Research Funding; Sobi: Consultancy; Takeda: Consultancy, Research Funding. Coppens:Roche: Research Funding; Portola/Alexion: Research Funding; Sanquin Blood Supply: Research Funding; uniQure: Research Funding; NovoNordisk: Consultancy; Pfizer: Consultancy; Sobi: Consultancy; Medcon International: Consultancy; MEDtalks: Consultancy; Bayer: Consultancy, Research Funding; CSL Behring: Consultancy, Research Funding; Daiichi Sankyo: Research Funding. O'Connell:uniQure: Consultancy; F. Hoffmann-La Roche Ltd, Novo Nordisk, SOBI: Speakers Bureau; SOBI: Research Funding. Pasi:Sanofi: Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia, Research Funding; BioMarin: Consultancy, Honoraria, Other: Grants, personal fees, and nonfinancial support; honoraria as member of scientific advisory boards and symposia, Research Funding; uniQure: Other: Grants and nonfinancial support , Research Funding; ApcinteX: Consultancy, Other: Personal fees ; Takeda: Consultancy, Honoraria, Other: Personal fees; honoraria as member of scientific advisory boards and symposia ; Biotest: Consultancy, Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia; Catalyst Biosciences: Consultancy, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia; Novo Nordisk: Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia ; Octapharma: Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia , Speakers Bureau; Roche: Honoraria, Other; Sobi: Consultancy, Honoraria, Other; Tremeau: Consultancy. Kampmann:Uniqure: Research Funding, Speakers Bureau; Shire Pharmaceuticals: Speakers Bureau. Meijer:Pfizer: Research Funding; Sanquin: Speakers Bureau; Bayer: Speakers Bureau; Sanquin: Research Funding; Bayer: Research Funding; Boehringer Ingelheim: Speakers Bureau; BMS: Speakers Bureau; Aspen: Speakers Bureau; Uniqure: Consultancy. von Drygalski:Biomarin: Consultancy; Bioverativ/Sanofi Genzyme: Consultancy; NovoNordisk: Consultancy; Pfizer: Consultancy; uniQure: Consultancy; Hematherix Inc.: Membership on an entity's Board of Directors or advisory committees. Young:Genentech/Roche, Grifols, and Takeda: Research Funding; BioMarin, Freeline, Genentech/Roche, Grifols, Kedrion, Novo Nordisk, Sanofi Genzyme, Spark, Takeda, and UniQure: Honoraria; Bayer, CSL Behring, Freeline, UniQure: Consultancy. Hermans:WFH: Other; EAHAD: Other; LFB: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Speakers Bureau; CAF-DCF: Consultancy, Speakers Bureau; Biogen: Consultancy, Speakers Bureau; Sobi: Consultancy, Research Funding, Speakers Bureau; Shire, a Takeda company: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Octapharma: Consultancy, Speakers Bureau; Kedrion: Speakers Bureau. Astermark:Bayer, CSL Behring, Novo Nordisk, Octapharma, Roche, Sobi, Spark, Takeda, uniQure: Consultancy; uniQure: Research Funding. Klamroth:Bayer: Consultancy, Research Funding, Speakers Bureau; Biomarin: Consultancy, Research Funding, Speakers Bureau; CSL Behring: Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau; Octapharma: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Roche/Chugai: Consultancy, Speakers Bureau; Takeda/Shire: Consultancy, Research Funding, Speakers Bureau; Sobi: Consultancy, Speakers Bureau; Biotest: Speakers Bureau; LEO: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Lemons:uniQure: Research Funding. Visweshwar:Biogen Idec: Membership on an entity's Board of Directors or advisory committees. Escobar:Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; National Hemophilia Foundation: Consultancy, Membership on an entity's Board of Directors or advisory committees; Biomarin, Genetech/Roche, CSL Behring, Kedrion, Magellan Healthcare: Honoraria. Gomez:Global Blood Therapeutics: Speakers Bureau. Kruse-Jarres:CSL Behring, Genentech, Inc., Spark: Research Funding; Biomarin, Chugai Pharmaceutical Co., CSL Behring, CRISPR Therapeutics, Genentech, Inc.: Honoraria; F. Hoffmann-La Roche Ltd: Speakers Bureau; Biomarin, Chugai Pharmaceutical Co., CSL Behring, CRISPR Therapeutics, Genentech, Inc.: Consultancy. Kotowski:uniQure: Research Funding. Quon:Orthopaedic Institute for Children: Current Employment; Bayer: Honoraria; Biomarin: Honoraria, Speakers Bureau; Bioverativ/Sanofi: Honoraria, Speakers Bureau; Genentech, Inc./F. Hoffmann-La Roche Ltd: Honoraria, Speakers Bureau; Novo Nordisk: Honoraria, Speakers Bureau; Octapharma: Honoraria; Shire/Takeda: Speakers Bureau. Wang:Bayer: Honoraria; Takeda: Honoraria; Genentech: Honoraria; Biomarin: Honoraria; CSL Behring: Honoraria; Bioverativ Inc: Honoraria; Catalyst Biologics: Consultancy; NovoNordisk: Consultancy; Hema biologics / LFB: Consultancy. Wheeler:Takeda: Membership on an entity's Board of Directors or advisory committees; uniQure: Membership on an entity's Board of Directors or advisory committees; Biomarin: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees. Sawyer:uniQure: Current Employment, Current equity holder in publicly-traded company. Verweij:uniQure: Current Employment. Colletta:uniQure: Current Employment. Bajma:uniQure: Current Employment. Gut:uniQure: Current Employment. Miesbach:Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biomarin: Consultancy, Membership on an entity's Board of Directors or advisory committees; Freeline: Consultancy, Membership on an entity's Board of Directors or advisory committees; LFB: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; uniQure: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biotest: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding. OffLabel Disclosure: Etranacogene dezaparvovec is an investigational gene therapy

Siemens führt die „Werkzeugmaschinenwelt“ auf die nächste Stufe der digitalen Transformation: Zukunftstechnologien wie die neue Steuerungsgeneration „Sinumerk One“, Edge- und Cloudcomputing, Künstliche Intelligenz und Additive Manufacturing werden in das Portfolio integriert. Eine neue Edge-Applikation optimiert die Werkstückqualität.