Efficacy and Safety of Approved First-Line Tyrosine Kinase Inhibitor Treatments in Metastatic Renal Cell Carcinoma: A Network Meta-Analysis

Introduction This network meta-analysis aims to deliver an up-to-date, comprehensive efficacy and toxicity comparison of the approved first-line tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma (mRCC) in order to provide support for evidence-based treatment decisions. Previous NMAs of first-line mRCC treatments either predate the approval of all the first-line TKIs currently available or do not include evaluation of safety data for all treatments. Methods We performed a systematic literature review and network meta-analysis of phase II/III randomised controlled trials (RCTs) assessing approved first-line TKI therapies for mRCC. A random effects model with a frequentist approach was computed for progression-free survival (PFS) data and for the proportion of patients experiencing a maximum of grade 3 or 4 adverse events (AEs). Results The network meta-analysis of PFS demonstrated no significant differences between cabozantinib and either sunitinib (50 mg 4/2), pazopanib or tivozanib. The network meta-analysis indicated that in terms of grade 3 and 4 AEs, tivozanib had the most favourable safety profile and was associated with significantly less risk of toxicity than the other TKIs. Conclusion These network meta-analysis data demonstrate that cabozantinib, sunitinib, pazopanib and tivozanib do not significantly differ in their efficacy, but tivozanib is associated with a more favourable safety profile in terms of grade 3 or 4 toxicities. Consequently, the relative toxicity of these first-line TKIs may play a more significant role than efficacy comparisons in treatment decisions and in planning future RCTs

Entwicklung und Erprobung von Verfahren und Einrichtungen zum Explosions-und Staubschutz in hochmechanisierten Gewinnungsbetrieben und maschinellen Streckenvortrieben Abschlussbericht

Der konstruktive Explosionsschutz wird lediglich in Form von Wassertrogsperren gewaehrleistet, die sich in groesserer Entfernung von einem moeglichen Zuendereignis befinden. Die an Walzenschraemladern z.Z. vorhandene Beduesung ist nicht geeignet, die Anforderungen an die Staubbekaempfung zu erfuellen. Ziele des Vorhabens sind deswegen sowohl Verbesserungen des konstruktiven Explosionsschutzes in Form einer automatischen Explosionsloeschanlage als auch optimierte Staubbekaempfungsmassnahmen bei der schneidenden Gewinnung. Durch untertaegige Versuche wurde eine automatische Explosionsloeschanlage an Teilschnittmaschinen zur Betriebsreife entwickelt. Ausserdem wurde ein uebertragbares Gesamtkonzept zur Brandbekaempfung an Gewinnungsmaschinen erstellt. Am Walzenschraemlader wurde ebenfalls in Untertageeinsaetzen eine neuartige Ejektorbeduesung in Verbindung mit angepassten Systemen der Druckerhoehung erprobt und zur Betriebsreife weiterentwickelt. (orig.)The constructional explosion-protection is simply guaranteed in form of water-barriers that have to be placed in the highest distance of a possible ignition-source. The drum water-sprinklers shearer-loaders are equiped with at present not suitable to impregnate the demands of dust suppression. Scopes of the project are therefore not only improvements of the constructional explosion-protection in form of automatic explosion-extinguisher but also optimised measures for dust-protection by work with cutting winning. Undergrounding tests brought the result of insertable automatic explosion-extinguisher for roundheader machines. Besides that an transferable general-draft for firefighting at roundheader machines has been developed. Also at shearer loaders a new kind of water-jet fan in combination with an adjusted system of pressure increase has been approved and developed to the final production standard. (orig.)SIGLEAvailable from TIB Hannover: F94B1085+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman

Evidence of hemispheric specialization in marmosets (Callithrix penicillata) using tympanic membrane thermometry

Recent studies have employed tympanic thermometry to assess lateralization of cognitive and emotional functions in primates. However, no studies using this technique have investigated the possibility of hemispheric specialization in New World monkeys. Therefore, the aim of the present study was to investigate tympanic membrane (TM) temperature asymmetries and their possible correlation with stress responses in marmosets (Callithrix penicillata). Infrared TM thermometry was completed bilaterally in 24 animals (14 males and 10 females) during a stressful situation of capture and restraint. There were no significant differences between gender. A significant negative correlation was observed between TM temperature of the right ear and the number of captures (r = -0.633; P<0.001). Subjects with a more frequent previous history of captures (5 to 9 captures; N = 11) showed lower TM temperature when compared to those with fewer previous captures (1 to 4 captures; N = 13). No differences were observed for the left TM temperature. These results suggest that under intense emotional challenge (capture and restraint) there is a stronger activation of the neural structures situated in the right brain hemisphere. Taken together, the data reveal for the first time evidence of hemispheric specialization in emotional physiological processing in a New World monkey