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Immunogenicity and safety of concomitant administration of a measles, mumps and rubella vaccine (M-M-RvaxPro?) and a varicella vaccine (VARIVAX?) by intramuscular or subcutaneous routes at separate injection sites: a randomised clinical trial
Yves Gillet, Pirmin Habermehl, Stéphane Thomas, Cécile Eymin, Anne Fiquet
BMC Medicine , 2009, DOI: 10.1186/1741-7015-7-16
Abstract: An open-label randomised trial was performed in France and Germany. Healthy children, aged 12 to18 months, received single injections of M-M-RvaxPro and VARIVAX concomitantly at separate injection sites. Both vaccines were administered either intramuscularly (IM group, n = 374) or subcutaneously (SC group, n = 378). Immunogenicity was assessed before vaccination and 42 days after vaccination. Injection-site erythema, swelling and pain were recorded from days 0 to 4 after vaccination. Body temperature was monitored daily between 0 and 42 days after vaccination. Other adverse events were recorded up to 42 days after vaccination and serious adverse events until the second study visit.Antibody response rates at day 42 in the per-protocol set of children initially seronegative to measles, mumps, rubella or varicella were similar between the IM and SC groups for all four antigens. Response rates were 94 to 96% for measles, 98% for both mumps and rubella and 86 to 88% for varicella. For children initially seronegative to varicella, 99% achieved the seroconversion threshold (antibody concentrations of ≥ 1.25 gpELISA units/ml). Erythema and swelling were the most frequently reported injection-site reactions for both vaccines. Most injection-site reactions were of mild intensity or small size (≤ 2.5 cm). There was a trend for lower rates of injection-site erythema and swelling in the IM group. The incidence and nature of systemic adverse events were comparable for the two routes of administration, except varicella-like rashes, which were less frequent in the IM group.The immunogenicities of M-M-RvaxPro and VARIVAX administered by the intramuscular route were comparable with those following subcutaneous administration, and the tolerability of the two vaccines was comparable regardless of administration route. Integration of both administration routes in the current European indications for the two vaccines will now allow physicians in Europe to choose their preferred administr
Codon usage in vertebrates is associated with a low risk of acquiring nonsense mutations
Pirmin Schmid, Willy A Flegel
Journal of Translational Medicine , 2011, DOI: 10.1186/1479-5876-9-87
Abstract: We developed an event based model to calculate the risk of acquiring nonsense mutations in coding sequences. Complete coding sequences and genomes of 40 eukaryotes were analyzed for GC and CpG content, codon usage, and the associated risk of acquiring nonsense mutations. We included one species per genus for all eukaryotes with available reference sequence.We discovered that the codon usage bias detected in genomes of high GC content decreases the risk of acquiring nonsense mutations (Pearson's r = -0.95; P < 0.0001). In the genomes of all examined vertebrates, including humans, this risk was lower than expected (0.93 ± 0.02; mean ± SD) and lower than the risk in genomes of non-vertebrates (1.02 ± 0.13; P = 0.019).While the maintenance of a high GC content is energetically costly, it is associated with a codon usage bias harboring a low risk of acquiring nonsense mutations. The reduced exposure to this risk may contribute to the fitness of vertebrates.Codon usage bias in genomes is relevant for organisms. It influences the translation speed and thus gene expression [1]. Artificially deoptimized codon usage can decrease gene expression and create an attenuated viral virulence that may be used for vaccine production [2]. HIV-1 modifies the tRNA pool of the infected cells to increase translation efficiency of its own genes [3]. Initial studies on codon usage bias were based on few genes in single species: lists of the codon usage [4], determination of the number of codons used in genes [5], and models, such as the codon adaptation index (CAI). The CAI compared the codon usage of each gene with an "optimal" codon usage, which is inferred from high-expression gene sets [6]. Whole genome sequencing data and newer algorithms have allowed researchers to overcome previous limitations, study more genes, and classify genes in more detailed categories [7]. Codon usage bias is associated with tRNA concentration [8] and also the GC content of genomes [9-12].Loss-of-function mutat
Redetermination of tantalum pentabromide, (TaBr5)2
Katja Habermehl,Ingo Pantenburg,Gerd Meyer
Acta Crystallographica Section E , 2010, DOI: 10.1107/s1600536810032538
Abstract: Crystals of di-μ-bromido-bis[tetrabromidotantalum(V)], (TaBr5)2, were obtained by recrystallization at 773 K. A first crystal structure study of (TaBr5)2 was reported by Rolsten [J. Am. Chem. Soc. (1958), 80, 2952–2953], who analysed the powder diffraction pattern and came to the conclusion that it crystallizes isotypically with (NbBr5)2 in a primitive orthorhombic cell. These findings are not in agreement with our current results of a monoclinic C-centred structure. (TaBr5)2 is isotypic with α-(NbCl5)2. The crystal structure contains [TaBr6] octahedra sharing common edges forming [TaBr5]2 dimers. Two crystallographically independent dimers with symmetries m and 2/m and Ta...Ta distances of 4.1574 (11) and 4.1551 (15) , respectively, are present in the structure.
Effective sampling for large-scale automated writing evaluation systems
Nicholas Dronen,Peter W. Foltz,Kyle Habermehl
Computer Science , 2014,
Abstract: Automated writing evaluation (AWE) has been shown to be an effective mechanism for quickly providing feedback to students. It has already seen wide adoption in enterprise-scale applications and is starting to be adopted in large-scale contexts. Training an AWE model has historically required a single batch of several hundred writing examples and human scores for each of them. This requirement limits large-scale adoption of AWE since human-scoring essays is costly. Here we evaluate algorithms for ensuring that AWE models are consistently trained using the most informative essays. Our results show how to minimize training set sizes while maximizing predictive performance, thereby reducing cost without unduly sacrificing accuracy. We conclude with a discussion of how to integrate this approach into large-scale AWE systems.
Patient Self-Management of Oral Anticoagulation with Vitamin K Antagonists in Everyday Practice: Efficacy and Safety in a Nationwide Long-Term Prospective Cohort Study
Michael Nagler, Lucas M. Bachmann, Pirmin Schmid, Pascale Raddatz Müller, Walter A. Wuillemin
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0095761
Abstract: Patient self-management (PSM) of oral anticoagulation is under discussion, because evidence from real-life settings is missing. Using data from a nationwide, prospective cohort study in Switzerland, we assessed overall long-term efficacy and safety of PSM and examined subgroups. Data of 1140 patients (5818.9 patient-years) were analysed and no patient were lost to follow-up. Median follow-up was 4.3 years (range 0.2–12.8 years). Median age at the time of training was 54.2 years (range 18.2–85.2) and 34.6% were women. All-cause mortality was 1.4 per 100 patient-years (95% CI 1.1–1.7) with a higher rate in patients with atrial fibrillation (2.5; 1.6–3.7; p<0.001), patients>50 years of age (2.0; 1.6–2.6; p<0.001), and men (1.6; 1.2–2.1; p = 0.036). The rate of thromboembolic events was 0.4 (0.2–0.6) and independent from indications, sex and age. Major bleeding were observed in 1.1 (0.9–1.5) per 100 patient-years. Efficacy was comparable to standard care and new oral anticoagulants in a network meta-analysis. PSM of properly trained patients is effective and safe in a long-term real-life setting and robust across clinical subgroups. Adoption in various clinical settings, including those with limited access to medical care or rural areas is warranted.
Stable alterations of CD44 isoform expression in prostate cancer cells decrease invasion and growth and alter ligand binding and chemosensitivity
Kui Yang, Yaqiong Tang, Gabriel K Habermehl, Kenneth A Iczkowski
BMC Cancer , 2010, DOI: 10.1186/1471-2407-10-16
Abstract: Using retroviral gene delivery to PC-3M PCa cells, we expressed luciferase-only, enforced CD44s re-expression as a fusion protein with luciferase at its C-terminus or as a protein separate from luciferase, or knocked down CD44v7-10 by RNAi. Invasion, migration, proliferation, soft agar colony formation, adhesion, Docetaxel sensitivity, and xenograft growth assays were carried out. Expression responses of merlin, a CD44 binding partner, and growth-permissive phospho-merlin, were assessed by western blot.Compared to luciferase-only PC-3M cells, all three treatments reduced invasion and migration. Growth and soft agar colony formation were reduced only by re-expression of CD44s as a separate or fusion protein but not CD44v7-10 RNAi. Hyaluronan and osteopontin binding were greatly strengthened by CD44s expression as a separate protein, but not a fusion protein. CD44v7-10 RNAi in PC-3M cells caused marked sensitization to Docetaxel; the two CD44s re-expression approaches caused minimal sensitization. In limited numbers of mouse subcutaneous xenografts, all three alterations produced only nonsignificant trends toward slower growth compared with luciferase-only controls. The expression of CD44s as a separate protein, but not a fusion protein, caused emergence of a strongly-expressed, hypophosphorylated species of phospho-merlin.Stable re-expression of CD44s reduces PCa growth and invasion in vitro, and possibly in vivo, suggesting CD44 alterations have potential as gene therapy. When the C-terminus of CD44s is fused to another protein, most phenotypic effects are lessened, particularly hyaluronan adhesion. Finally, CD44v7-10, although it was not functionally significant for growth, may be a target for chemosensitization.About 30% of cases of prostate cancer (PCa) undergo transition from quiescent to aggressive. In this transition, altered expression of adhesion glycoproteins such as CD44 occurs allowing tumor cells to detach, interact with proteins that digest stromal matr
Plant extracts for topic therapy of Bothrops alternatus envenomation
Melo, Marilia Martins;Lúcia, Maria;Habermehl, Gerhard G.;
Revista Brasileira de Farmacognosia , 2007, DOI: 10.1590/S0102-695X2007000100007
Abstract: two plants were investigated for their properties against the local effects of bothrops alternatus venom in rabbits, namely curcuma longa l. (zingiberaceae) and aristolochia cymbifera l. (aristolochiaceae). the experiments showed that, curcuma longa extract topic application was the most effective treatment against local symptoms (edema, hemorrhages and necrosis) caused by bothrops venom, whereas the results with aristolochia cymbifera l. were doubtful, because they led to a larger damaged area during the early phase of the inflammation process, besides skin mummification.
Chemoradiation in patients with isolated recurrent pancreatic cancer - therapeutical efficacy and probability of re-resection
Habermehl Daniel,Brecht Ingo C,Bergmann Frank,Welzel Thomas
Radiation Oncology , 2013, DOI: 10.1186/1748-717x-8-27
Abstract: Background In the present retrospective analysis we analysed the therapeutic outcome of a set of patients, who were treated with chemoradiation (CRT) for recurrent pancreatic cancer (RPC) in a single institution. Patients and Methods Forty-one patients had a history of primary resection for pancreatic cancer. In case of an unresectable recurrency patients were treated with CRT at our institution between 2002 and 2010 with a median dose of 48.4 Gy (range 39.6–54 Gy). Concurrent chemotherapy regimes included Gemcitabine (GEM) in 37/41 patients (90%) and Fluorouracil (FU) or Capecitabine (CAP) in 4/41 patients (10%). Patients were re-evaluated after CRT with computed tomography and/or explorative laparotomy. During re-resection or laparotomy 15 patients received an additional intraoperative radiotherapy (IORT) with a median dose of 15 Gy (range 12–15 Gy). Median age was 65 years (range 39–76 years) and there were 26 male and 15 female patients. Results The median overall survival (mOS), local control (LC) and progression-free survival (PFS) were 16.1, 13.8 and 6.9 months respectively for all patients after the first day of CRT. Re-resection was possible in five patients (12%) and a complete remission (CR) as defined by tumor-free biopsy was seen in 6 patients (15%). When re-resection could be achieved after CRT mOS was improved to 28.3 months (n = 5 patients, 95%-CI 10.2 – 46.3 months). Patients receiving IORT had a significantly improved mOS compared to no IORT (p = 0.034). Fifteen patients (37%) experienced a local tumour progression and main site of distant metastasis was the liver (11 patients, 27%).Overall treatment-related toxicity was mild, grade III hematologic toxicity was observed in 11 patients (27%). Conclusion In summary we observed a good therapeutic response with mild to moderate toxicity levels for CRT in RPC. Overall survival and PFS were clearly improved in case of induction of a complete remission (tumor-free biopsies) or after achieving a re-resection, thus providing a curative intended therapy even in case of disease recurrence.
Efficacy and toxicity of whole brain radiotherapy in patients with multiple cerebral metastases from malignant melanoma
Hauswald Henrik,Dittmar Jan-Oliver,Habermehl Daniel,Rieken Stefan
Radiation Oncology , 2012, DOI: 10.1186/1748-717x-7-130
Abstract: Background To retrospectively access outcome and toxicity of whole brain radiotherapy (WBRT) in patients with multiple brain metastases (BM) from malignant melanoma (MM). Patients and methods Results of 87 patients (median age 58 years; 35 female, 52 male) treated by WBRT for BM of MM between 2000 and 2011 were reviewed. Total dose applied was either 30 Gy in 10 fractions (n = 56) or 40 Gy in 20 fractions (n = 31). All but 9 patients suffered from extra-cerebral metastases. Prior surgical resection of BM was performed in 18 patients, salvage stereotactic radiosurgery in 13 patients. Results Mean follow-up was 8 months (range, 0–57 months), the 6- and 12-months overall-(OS) survival rates were 29.2% and 16.5%, respectively. The median OS was 3.5 months. In cerebral follow-up imaging 6 (11) patients showed a complete (partial) remission, while 11 (17) patients had stable disease (intra-cerebral tumor progression). In comparison of total dose, the group treated with 40 Gy in 20 fractions achieved a significant longer OS (p = 0.003, median 3.1 vs. 5.6 months). Furthermore, DS-GPA score (p < 0.001) as well as RPA class (p < 0.001) influenced significantly on OS and patients had a significantly longer OS after surgical resection (p = 0.001, median 3.0 vs. 5.8 months, multivariate p = 0.007). Having extra-cerebral metastases didn't significantly impact on OS (p = 0.21). Conclusion Treatment of BM from MM with WBRT is tolerated well and some remissions of BM could be achieved. An advantage for higher treatment total doses was seen. However, outcome is non-satisfying, and further improvements in treatment of BM from MM are warranted.
Connection of European particle therapy centers and generation of a common particle database system within the European ULICE-framework
Kessel Kerstin A,Bougatf Nina,Bohn Christian,Habermehl Daniel
Radiation Oncology , 2012, DOI: 10.1186/1748-717x-7-115
Abstract: Background To establish a common database on particle therapy for the evaluation of clinical studies integrating a large variety of voluminous datasets, different documentation styles, and various information systems, especially in the field of radiation oncology. Methods We developed a web-based documentation system for transnational and multicenter clinical studies in particle therapy. 560 patients have been treated from November 2009 to September 2011. Protons, carbon ions or a combination of both, as well as a combination with photons were applied. To date, 12 studies have been initiated and more are in preparation. Results It is possible to immediately access all patient information and exchange, store, process, and visualize text data, any DICOM images and multimedia data. Accessing the system and submitting clinical data is possible for internal and external users. Integrated into the hospital environment, data is imported both manually and automatically. Security and privacy protection as well as data validation and verification are ensured. Studies can be designed to fit individual needs. Conclusions The described database provides a basis for documentation of large patient groups with specific and specialized questions to be answered. Having recently begun electronic documentation, it has become apparent that the benefits lie in the user-friendly and timely workflow for documentation. The ultimate goal is a simplification of research work, better study analyses quality and eventually, the improvement of treatment concepts by evaluating the effectiveness of particle therapy.
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