Functional Recovery Not Correlated with Axon Regeneration through Olfactory Ensheathing Cell- Seeded Scaffolds in a Model of Acute Spinal Cord Injury

Haktan Altinova,Sven Möllers,Ronald Deumens,Jose Gerardo-Nava,Tobias Führmann,Sabien Geraldine Antonia van Neerven,Ahmet Bozkurt,Christian Andreas Mueller,Hans Joachim Hoff,Ingo Heschel,Joachim Weis,G 한국조직공학과 재생의학회 2016 조직공학과 재생의학 Vol.13 No.5

The implantation of bioengineered scaffolds into lesion-induced gaps of the spinal cord is a promising strategy for promoting functional tissue repair because it can be combined with other intervention strategies. Our previous investigations showed that functional improvement following the implantation of a longitudinally microstructured collagen scaffold into unilateral mid-cervical spinal cord resection injuries of adult Lewis rats was associated with only poor axon regeneration within the scaffold. In an attempt to improve graft-host integration as well as functional recovery, scaffolds were seeded with highly enriched populations of syngeneic, olfactory bulb-derived ensheathing cells (OECs) prior to implantation into the same lesion model. Regenerating neurofilament-positive axons closely followed the trajectory of the donor OECs, as well as that of the migrating host cells within the scaffold. However, there was only a trend for increased numbers of regenerating axons above that supported by non-seeded scaffolds or in the untreated lesions. Nonetheless, significant functional recovery in skilled forelimb motor function was observed following the implantation of both seeded and non-seeded scaffolds which could not be correlated to the extent of axon regeneration within the scaffold. Mechanisms other than simple bridging of axon regeneration across the lesion must be responsible for the improved motor function.

Advanced dual fluidized bed steam gasification of wood and lignite with calcite as bed material

Florian Benedikt,Josef Fuchs,Johannes Christian Schmid,Stefan Müller,Hermann Hofbauer 한국화학공학회 2017 Korean Journal of Chemical Engineering Vol.34 No.9

This paper presents experimental results with a new generation of a 100 kWth dual fluidized bed steam gasification pilot plant with calcite as bed material, converting wood and lignite in separate test runs into product gas. The results are compared to experiments with the same fuels with olivine as bed material and the previous generation of the gasification pilot plant at TU Wien. The highly catalytic active calcium oxide shifted the product gas composition towards higher hydrogen and carbon dioxide and lower carbon monoxide content. The tar amount was decreased and the tar composition changed, resulting in lower tar dew points. The dust content in the product gas was reduced with the advanced pilot plant design with calcite in comparison to the classic design with olivine. Therefore, attrition of bed material was decreased by utilizing the advanced design and calcite with its benefits can be used without profuse continuous replacement of bed material.

Radiological and Clinical Outcomes of Balloon Kyphoplasty versus Radiofrequency Kyphoplasty in the Treatment of Vertebral Compression Fractures

Marcel Winkelmann,Thassia Mavropoulos,Sebastian Decker,Mohamed Omar,Christian Krettek,Christian Walter Müller 대한척추외과학회 2018 Asian Spine Journal Vol.12 No.5

Study Design: Retrospective cohort analysis Purpose: Comparison of balloon kyphoplasty (BKP) and radiofrequency kyphoplasty (RFK) with respect to height restoration of the fractured vertebral bodies and the pain relief experienced after the surgical procedure. Overview of Literature: BKP and RFK both offer safe, time-saving, and potent treatment options for vertebral compression fractures, but neither of these methods demonstrated any key advantage over the other yet. Methods: We performed a retrospective analysis of a cohort of 156 patients (mean age, 73±11 years) with 252 fractured vertebral bodies treated with kyphoplasty. Pain intensity was measured using a Visual Analogue Scale. Preoperative and postoperative computed tomography images were analyzed and gauged using modified bisegmental Cobb angle, vertebral angle, as well as anterior (Ha), middle (Hm), and posterior (Hp) vertebral body heights. Results: The mean postoperative pain relief was 5.1±1.8, which was maintained over the entire follow-up period. There were no significant differences in the pain relief between BKP and RFK. Postoperative changes in the vertebral angle (−1.3°±3.3°, p <0.001) and Ha, Hm, and Hp vertebral body heights (Ha, 1.5±2.9 mm; Hm, 2.1±2.9 mm; Hp, 0.9±2.1 mm; p <0.001) were significant. However, the initial height restoration could not be maintained by the 6-week and 1-year follow-up. Neither BKP nor RFK could achieve a clinically relevant advantage over each other. There was no correlation between pain relief and height restoration after kyphoplasty. Conclusions: Both BKP and RFK had comparable beneficial clinical and radiological effects in the treatment of vertebral compression fractures. However, neither the actual extent of height restoration nor its loss seems to affect the marked pain relief.

Increased pore size of scaffolds improves coating efficiency with sulfated hyaluronan and mineralization capacity of osteoblasts

Jan Krieghoff,Ann-Kristin Picke,Juliane Salbach-Hirsch,Sandra Rother,Christiane Heinemann,Ricardo Bernhardt,Christian Kascholke,Stephanie Möller,Martina Rauner,Matthias Schnabelrauch,Vera Hintze,Diete 한국생체재료학회 2020 생체재료학회지 Vol.24 No.1

Background: Delayed bone regeneration of fractures in osteoporosis patients or of critical-size bone defects after tumor resection are a major medical and socio-economic challenge. Therefore, the development of more effective and osteoinductive biomaterials is crucial. Methods: We examined the osteogenic potential of macroporous scaffolds with varying pore sizes after biofunctionalization with a collagen/high-sulfated hyaluronan (sHA3) coating in vitro. The three-dimensional scaffolds were made up from a biodegradable three-armed lactic acid-based macromer (TriLA) by crosspolymerization. Templating with solid lipid particles that melt during fabrication generates a continuous pore network. Human mesenchymal stem cells (hMSC) cultivated on the functionalized scaffolds in vitro were investigated for cell viability, production of alkaline phosphatase (ALP) and bone matrix formation. Statistical analysis was performed using student’s t-test or two-way ANOVA. Results: We succeeded in generating scaffolds that feature a significantly higher average pore size and a broader distribution of individual pore sizes (HiPo) by modifying composition and relative amount of lipid particles, macromer concentration and temperature for cross-polymerization during scaffold fabrication. Overall porosity was retained, while the scaffolds showed a 25% decrease in compressive modulus compared to the initial TriLA scaffolds with a lower pore size (LoPo). These HiPo scaffolds were more readily coated as shown by higher amounts of immobilized collagen (+ 44%) and sHA3 (+ 25%) compared to LoPo scaffolds. In vitro, culture of hMSCs on collagen and/or sHA3-coated HiPo scaffolds demonstrated unaltered cell viability. Furthermore, the production of ALP, an early marker of osteogenesis (+ 3-fold), and formation of new bone matrix (+ 2.5-fold) was enhanced by the functionalization with sHA3 of both scaffold types. Nevertheless, effects were more pronounced on HiPo scaffolds about 112%. Conclusion: In summary, we showed that the improvement of scaffold pore sizes enhanced the coating efficiency with collagen and sHA3, which had a significant positive effect on bone formation markers, underlining the promise of using this material approach for in vivo studies.

International case study comparing PSA modeling approaches for nuclear digital I&C – OECD/NEA task DIGMAP

Porthin Markus,신성민,Quatrain Richard,Tyrväinen Tero,Sedlak Jiri,Brinkman Hans,Müller Christian,Picca Paolo,Jaros Milan,Natarajan Venkat,Piljugin Ewgenij,Demgné Jeanne 한국원자력학회 2023 Nuclear Engineering and Technology Vol.55 No.12

Nuclear power plants are increasingly being equipped with digital I&C systems. Although some probabilistic safety assessment (PSA) models for the digital I&C of nuclear power plants have been constructed, there is currently no specific internationally agreed guidance for their modeling. This paper presents an initiative by the OECD Nuclear Energy Agency called “Digital I&C PSA – Comparative application of DIGital I&C Modelling Approaches for PSA (DIGMAP)”, which aimed to advance the field towards practical and defendable modeling principles. The task, carried out in 2017–2021, used a simplified description of a plant focusing on the digital I&C systems important to safety, for which the participating organizations independently developed their own PSA models. Through comparison of the PSA models, sensitivity analyses as well as observations throughout the whole activity, both qualitative and quantitative lessons were learned. These include insights on failure behavior of digital I&C systems, experience from models with different levels of abstraction, benefits from benchmarking as well as major contributors to the core damage frequency and those with minor effect. The study also highlighted the challenges with modeling of large common cause component groups and the difficulties associated with estimation of key software and common cause failure parameters

Intravenous Thrombolysis in Patients with Stroke Taking Rivaroxaban Using Drug Specific Plasma Levels: Experience with a Standard Operation Procedure in Clinical Practice

David J. Seiffge,Christopher Traenka,Alexandros A. Polymeris,Sebastian Thilemann,Benjamin Wagner,Lisa Hert,Mandy D. Müller,Henrik Gensicke,Nils Peters,Christian H. Nickel,Christoph Stippich,Raoul Sutt 대한뇌졸중학회 2017 Journal of stroke Vol.19 No.3

Background and Purpose Standard operating procedures (SOP) incorporating plasma levels of rivaroxaban might be helpful in selecting patients with acute ischemic stroke taking rivaroxaban suitable for IVthrombolysis(IVT) or endovascular treatment (EVT). Methods This was a single-center explorative analysis using data from the Novel-Oral-Anticoagulants-in-Stroke-Patients-registry (clinicaltrials.gov:NCT02353585) including acute stroke patients taking rivaroxaban(September 2012 to November 2016). The SOP included recommendation, consideration, and avoidance of IVT if rivaroxaban plasma levels were <20 ng/mL, 20‒100 ng/mL, and >100 ng/mL, respectively, measured with a calibrated anti-factor Xa assay. Patients with intracranial artery occlusion were recommended IVT+EVT or EVT alone if plasma levels were ≤100 ng/mL or >100 ng/mL, respectively. We evaluated the frequency of IVT/EVT, door-to-needle-time (DNT), and symptomatic intracranial or major extracranial hemorrhage. Results Among 114 acute stroke patients taking rivaroxaban, 68 were otherwise eligible for IVT/EVT of whom 63 had plasma levels measured (median age 81 years, median baseline National Institutes of Health Stroke Scale 6). Median rivaroxaban plasma level was 96 ng/mL (inter quartile range [IQR] 18‒259 ng/mL) and time since last intake 11 hours (IQR 4.5‒18.5 hours). Twenty-two patients (35%) received IVT/EVT (IVT n=15, IVT+EVT n=3, EVT n=4) based on SOP. Median DNT was 37 (IQR 30‒60) minutes. None of the 31 patients with plasma levels >100ng/mL received IVT. Among 14 patients with plasma levels ≤100 ng/mL, the main reason to withhold IVT was minor stroke (n=10). No symptomatic intracranial or major extracranial bleeding occurred after treatment. Conclusions Determination of rivaroxaban plasma levels enabled IVT or EVT in one-third of patients taking rivaroxaban who would otherwise be ineligible for acute treatment. The absence of major bleeding in our pilot series justifies future studies of this approach.

Testing for an excessive number of zeros in time series of bounded counts

Kim, Hee-Young,Weiß, Christian H.,Mö,ller, Tobias A. Springer-Verlag 2018 Statistical methods & applications Vol.27 No.4