Year of publication
- Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID) (2011)
- Introduction Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard of care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard of care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin's lymphoma in a real-life clinical setting. Methods Patients who received rituximab having shown an inadequate response to standard of care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators. Results A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0% with systemic lupus erythematosus, 15.7% antineutrophil cytoplasmic antibody-associated vasculitides, 15.1% multiple sclerosis and 10.0% pemphigus) from 42 centres received a mean dose of 2440 mg of rituximab over a median (range) of 194 (180 to 1407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3% of patients showed no response, 45.1% showed a partial response and 41.6% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician's visual analogue scale; mean improvement from baseline of 12.1 mm). Conclusions Data from this registry indicate that rituximab is a commonly employed, well-tolerated therapy with potential beneficial effects in standard of care-refractory autoimmune diseases, and support the results from other open-label, uncontrolled studies. Additional file 1: Supplemental tables. Table A1. Duration of follow-up from first rituximab infusion to last control visit by diagnosis. Table A2. Number of rituximab infusions by diagnosis.
- The ALICE TPC : a large 3-dimensional tracking device with fast readout for ultra-high multiplicity events (2010)
- The design, construction, and commissioning of the ALICE Time-Projection Chamber (TPC) is described. It is the main device for pattern recognition, tracking, and identification of charged particles in the ALICE experiment at the CERN LHC. The TPC is cylindrical in shape with a volume close to 90 m3 and is operated in a 0.5 T solenoidal magnetic field parallel to its axis. In this paper we describe in detail the design considerations for this detector for operation in the extreme multiplicity environment of central Pb–Pb collisions at LHC energy. The implementation of the resulting requirements into hardware (field cage, read-out chambers, electronics), infrastructure (gas and cooling system, laser-calibration system), and software led to many technical innovations which are described along with a presentation of all the major components of the detector, as currently realized. We also report on the performance achieved after completion of the first round of stand-alone calibration runs and demonstrate results close to those specified in the TPC Technical Design Report.
- Die Vertragsbeziehung zwischen Investoren und Venture Capital-Fonds : eine empirische Untersuchung des europäischen Venture Capital-Marktes (2002)
- Gamma measurements with the 4pi BaF2 detector for the FRANZ facility (2008)
- The current performance of a 4π barium fluoride gamma detector consisting of 41 modules is evaluated. It will be used to measure neutron capture events in different samples that are exposed to a neutron beam that is expected to contain up to 10^7 neutrons/(cm^2 sec). The capture cross-sections acquired in this experiment will be relevant to a multitude of different areas, for example to s-process studies, or accelerator-driven systems. The detector array was re-mounted after having been moved from Karlsruhe to Frankfurt and in the course of this process, the detector modules have been checked for their current detection properties. Every module consists of a BaF2 crystal, a photomultiplier tube connected to the crystal by sillicon oil and a voltage divider to drive the PMT, so each of them is already an individual gamma detector. Using Cobalt-60 and Caesium-137 test sources the energy resolution and - more importantly - the time resolution of every module has been determined; the results are presented in this work and compared to previous data taken at the time the detector was built initially in the mid-1980s.
- Die Welt jenseits der Oszillografen : ein Streitgespräch zwischen dem Hirnforscher Wolf Singer und dem Philosophen Marcus Willaschek (2005)
- Neurowissenschaftler fordern einen illusionslosen Umgang mit Begriffen wie Willensfreiheit und Bewusstsein. Philosophen kritisieren offen die Thesen von Hirnforschern. Stehen sich diese Positionen unversöhnlich gegenüber? Wo gibt es Möglichkeiten einer Annäherung, gar einer Kooperation? Der Religionsphilosoph Prof. Dr. Thomas M. Schmidt und der Biologe Stefan Kieß loten die Situation in Frankfurt aus; ihre Gesprächspartner sind der Hirnforscher Prof. Dr. Wolf Singer (links), Direktor am Max-Planck-Institut für Hirnforschung, und Prof. Dr. Marcus Willaschek (rechts), Philosoph an der Universität Frankfurt.
- Transition of properties from a proton beam to a neutron beam using the 7 Li (p, n) 7 Be reaction as an example (2011)
- As a part of this thesis, a Monte Carlo-based code has been developed capable of simulating the transition of proton beam properties to neutron beam properties as it occurs in the Li-7(p, n)Be-7 reaction. It is able to reproduce not only the angle-integrated energy distributions but it is also capable of predicting the angle-dependent neutron spectra as measured at Forschungszentrum Karlsruhe (Karlsruhe, Germany) and Physikalisch-Technische Bundesanstalt (Braunschweig, Germany). Since the code retains all three spatial dimensions as well as all three velocity dimensions, it provides very detailed information on the neutron beam. The resulting data can aid in many different aspects, for example it can be used in shielding construction, or for lithium target design. In this work, the code is used to predict the neutron beam properties expected at the Frankfurt Neutron Source at Stern-Gerlach-Zentrum (FRANZ) facility. For different proton beam energies, the neutron distribution in x/p_x, y/p_y, and z/p_z is shown as well as a Mollweide projection, which illustrates the kinematic collimation effect that limits the neutron cone opening angle to less than 180 degree.
- Das Usutu-Virus als Ursache von Massensterben bei Amseln Turdus merula und anderen Vogelarten in Europa: Erfahrungen aus fünf Ausbrüchen zwischen 2001 und 2011 (2012)
- Das Usutu-Virus (USUV) ist ein durch Stechmücken der Gattung Culex übertragenes Flavivirus. Es wurde wahrscheinlich durch Zugvögel oder Stechmücken nach Europa eingeschleppt und hat sich inzwischen dauerhaft in der einheimischen Stechmücken-und Vogelfauna etabliert. Seit seinem Erstnachweis 2001 in Österreich hat das USUV fünf größere Ausbrüche mit USUV-assoziierten Vogelsterben, vor allem unter Amseln und in Volieren gehaltenen Eulen, sowie vermutlich kleinere Ausbrüche ohne augenfälliges Vogelsterben verursacht. In unserer Übersicht stellen wir das aktuelle Wissen zum Erreger, den Stechmücken als Vektoren und den Vögeln als Hauptwirten vor. Die Auswertung bislang publizierter Studien ergab, dass in der letzten Dekade in Europa, im Zusammenhang mit USUV-Ausbrüchen, über 3050 Vogelindividuen aus 129 Arten und unterschiedlichsten Ordnungen auf USUV-Infektionen untersucht worden sind. Davon wurden 48 Arten positiv getestet, überwiegend Singvögel, Eulen und Greifvögel. Am häufigsten war die Amsel, danach Haussperling, Mönchsgrasmücke, Bart- und Habichtskauz betroffen. Unter den 48 USUV-positiven Arten betrafen 39 frei lebende und neun in Gefangenschaft gehaltene Arten. Mögliche Ausbreitungswege des Erregers von Afrika nach Europa sowie innerhalb Europas werden diskutiert. Amseln und andere Singvögel sind anscheinend besonders anfällig für USUV. Möglicherweise sind sie zur Hauptflugzeit der Stechmücken aufgrund ihres Mauser- und Ernährungszustandes immungeschwächt und anfälliger für einen Virenbefall.
- Translation and adaptation of an international questionnaire to measure usage of complementary and alternative medicine (I-CAM-G) (2012)
- BACKGROUND: The growing body of data on prevalence of complementary and alternative medicine (CAM) usage means there is a need to standardize measurement on an international level. An international team has published a questionnaire0020 (I-CAM-Q), but no validation has yet been provided. The aim of the present study was to provide a German measurement instrument for CAM usage (I-CAM-G) which closely resembles the original English version, and to assess it's performance in two potential samples for measuring CAM usage. METHODS: The English I-CAM-Q questionnaire was translated into German, and adapted slightly. The resulting I-CAM-G questionnaire was then pre-tested on N=16 healthy volunteers, and 12 cognitive interviews were carried out. The questionnaire was employed in a sample of breast cancer patients (N=92, paper and pencil), and a sample from the general population (N=210, internet survey). Descriptive analyses of items and missing data, as well as results from the cognitive interviews, are presented in this paper. RESULTS: The translated questionnaire had to be adapted to be consistent with the German health care system. All items were comprehensible, whereby some items were unambiguous (e.g. CAM use yes/no, helpfulness), while others gave rise to ambiguous answers (e.g. reasons for CAM use), or high rates of missing data (e.g. number of times the CAM modality had been used during the last 3 months). 78% of the breast cancer patients and up to 85% of a sample of the general population had used some form of CAM. CONCLUSIONS: Following methodologically sound and comprehensive translation, adaptation and assessment processes using recognized translation procedures, cognitive interviews, and studying the performance of the questionnaire in two samples, we arrived at a German questionnaire for measuring CAM use which is comparable with the international (English) version. The questionnaire appropriately measures CAM use, with some items being more appropriate than others. We recommend the development of a short version.
- From bench to bedside: preclinical evaluation of a self-inactivating gammaretroviral vector for the gene therapy of X-linked chronic granulomatous disease (2013)
- Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by impaired antimicrobial activity in phagocytic cells. As a monogenic disease affecting the hematopoietic system, CGD is amenable to gene therapy. Indeed in a phase I/II clinical trial, we demonstrated a transient resolution of bacterial and fungal infections. However, the therapeutic benefit was compromised by the occurrence of clonal dominance and malignant transformation demanding alternative vectors with equal efficacy but safety-improved features. In this work we have developed and tested a self-inactivating (SIN) gammaretroviral vector (SINfes.gp91s) containing a codon-optimized transgene (gp91(phox)) under the transcriptional control of a myeloid promoter for the gene therapy of the X-linked form of CGD (X-CGD). Gene-corrected cells protected X-CGD mice from Aspergillus fumigatus challenge at low vector copy numbers. Moreover, the SINfes.gp91s vector generates substantial amounts of superoxide in human cells transplanted into immunodeficient mice. In vitro genotoxicity assays and longitudinal high-throughput integration site analysis in transplanted mice comprising primary and secondary animals for 11 months revealed a safe integration site profile with no signs of clonal dominance.
- Genomic instability and myelodysplasia with monosomy 7 consequent to EVI1 activation after gene therapy for chronic granulomatous disease (2010)
- Gene-modified autologous hematopoietic stem cells (HSC) can provide ample clinical benefits to subjects suffering from X-linked chronic granulomatous disease (X-CGD), a rare inherited immunodeficiency characterized by recurrent, often life-threatening bacterial and fungal infections. Here we report on the molecular and cellular events observed in two young adults with X-CGD treated by gene therapy in 2004. After the initial resolution of bacterial and fungal infections, both subjects showed silencing of transgene expression due to methylation of the viral promoter, and myelodysplasia with monosomy 7 as a result of insertional activation of ecotropic viral integration site 1 (EVI1). One subject died from overwhelming sepsis 27 months after gene therapy, whereas a second subject underwent an allogeneic HSC transplantation. Our data show that forced overexpression of EVI1 in human cells disrupts normal centrosome duplication, linking EVI1 activation to the development of genomic instability, monosomy 7 and clonal progression toward myelodysplasia.