Partially Randomized, Non-Blinded Trial of DNA and MVA Therapeutic Vaccines Based on Hepatitis B Virus Surface Protein for Chronic HBV Infection

BACKGROUND: Chronic HBV infects 350 million people causing cancer and liver failure. We aimed to assess the safety and efficacy of plasmid DNA (pSG2.HBs) vaccine, followed by recombinant modified vaccinia virus Ankara (MVA.HBs), encoding the surface antigen of HBV as therapy for chronic HBV. A secondary goal was to characterize the immune responses. METHODS: Firstly 32 HBV e antigen negative (eAg(-)) participants were randomly assigned to one of four groups: to receive vaccines alone, lamivudine (3TC) alone, both, or neither. Later 16 eAg(+) volunteers in two groups received either 3TC alone or both 3TC and vaccines. Finally, 12 eAg(-) and 12 eAg(+) subjects were enrolled into higher-dose treatment groups. Healthy but chronically HBV-infected males between the ages of 15-25 who lived in the western part of The Gambia were eligible. Participants in some groups received 1 mg or 2 mg of pSG2.HBs intramuscularly twice followed by 5×10(7) pfu or 1.5×10(8) pfu of MVA.HBs intradermally at 3-weekly intervals with or without concomitant 3TC for 11-14 weeks. Intradermal rabies vaccine was administered to a negative control group. Safety was assessed clinically and biochemically. The primary measure of efficacy was a quantitative PCR assay of plasma HBV. Immunity was assessed by IFN-γ ELISpot and intracellular cytokine staining. RESULTS: Mild local and systemic adverse events were observed following the vaccines. A small shiny scar was observed in some cases after MVA.HBs. There were no significant changes in AST or ALT. HBeAg was lost in one participant in the higher-dose group. As expected, the 3TC therapy reduced viraemia levels during therapy, but the prime-boost vaccine regimen did not reduce the viraemia. The immune responses were variable. The majority of IFN-γ was made by antigen non-specific CD16(+) cells (both CD3(+) and CD3(-)). CONCLUSIONS: The vaccines were well tolerated but did not control HBV infection. TRIAL REGISTRATION: ISRCTN ISRCTN67270384

A new algorithm for real-time sub-structure pseudo-dynamic tests

The real-time sub-structure pseudo-dynamic test (real-time sub-structure PSD test) is a new testing procedure that is able to simulate the interaction between a sub-structure and its main structure. Applications are in qualification testing of structural control devices like tuned mass dampers (TMDs) or active mass dampers (AMDs), or payloads in aerospace systems like satellites (sub-structure) in rockets (structure). A stable, implicit time stepping scheme is required which must be formulated as acceleration control. In order to avoid iteration, a sub-stepping method is applied during each time step. Results of an analytical study on a vibrating 2-DOF sub-system on a 2-DOF structure show the effects of the number of sub steps and of an error force compensation that is necessary to compensate the unavoidable equilibrium error at the end of each time step. This study is representative of aerospace applications. One-to-one application to buildings with TMDs is possible

On real-time pseudo-dynamic sub-structure testing: algorithm, numerical and experimental results

The real-time pseudo-dynamic sub-structure (SubPSD) test is a new procedure for dynamic testing of structures. Here, the actual test specimen is a part, i.e. sub-structure, of a larger, complex system. The main structure is simulated on a computer which is in interaction with the test rig. One possible application is the qualification test of a payload (sub-structure) mounted in a carrier rocket (computer model). Consideration of the interaction between main- and sub-structure will yield more realistic results than conventional shaking table tests. This can be a good basis for a more effective, light-weight design of the payload. An algorithm is presented, which is based on the Newmark time domain solution of the equation of motion. It uses sub-stepping instead o iteration to reach equilibrium within each time step. This algorithm and a suitable hardware allow for true real-time performance of the SubPSD test, even with oscillatory sub-structures. Numerical studies are presented which demonstrate the accuracy but also the limits of the procedure. Experimental results of a 4 d.o.f. test model are compared to the numerical results

Pseudodynamischer-Echtzeit-Substruktur-Test: Algorithmus, numerische und experimentelle Ergebnisse

Der real-time pseudo-dynamic sub-structure (SubPSD) Test ist eine neue dynamische Testmethode. Das eigentliche Versuchsobjekt ist hier Teil eines größeren, komplexen Systems, d.h. eine Substruktur. Das übergeordnete Hauptsystem wird auf einem Computer simuliert, der in Interaktion mit dem Versuchsstand steht. Ein Anwendungsbeispiel ist der Qualifikationstest der Nutzlast (als Substruktur) auf einer Trägerrakete (Hauptsystem). Die Berücksichtigung der Interaktion zwischen Haupt- und Subsystem ergibt realistischere Daten als der konventionelle shaking table - Test. Solche Daten wären eine gute Grundlage für effizientere, leichtere Konstruktionen der Nutzlasten. Der im vorliegenden Artikel vorgestellte Algorithmus basiert auf der Lösung der Bewegungsgleichung im Zeitbereich Newmark. Sogenanntes sub-stepping wird anstelle einer Gleichgewichtsiteration innerhalb des Zeitschritts verwendet. Dieser Algorithmus und ein geeigneter Versuchsaufbau erlauben wirkliche Echtzeitanwendung des SubPSD - Tests, auch mit schwingenden Substrukturen. Mit Hilfe von numerischen Studien werden die Genauigkeit, Möglichkeiten und Grenzen dieser Methode demonstriert. Experimentelle Ergebnisse eines Vier-Freiheitsgrad-Modells werden den numerischen Ergebnissen gegenübergestellt

Realisation of Real-Time Pseudo-Dynamic Substructure Testing

The real-time pseudo-dynamic sub-structure test allows for most realistic dynamic testing of specimen from aerospace as well as structural engineering without the need of testing huge objects for representing entire systems. The specimen is tested in a truly dynamic manner as in shaking table tests, moreover, the structure surrounding and supporting the specimen is simulated by a computer. The computer model solves the equation of motion of the super-structure and calculates the excitation of the specimen. Measured reactions at the joint are fed back to the computer in a closed loop. The tests presented here are - to the knowledge of the authors - the first ones applied in true real time to an oscillatory specimen. The procedure is explained in brief, and the test demonstrate its capabilities. Finally, the hardware concept which enabled these tests is described