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Sökning: WFRF:(Kuhne J.)

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1.
  • Cossarizza, A., et al. (författare)
  • Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
  • 2019
  • Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 49:10, s. 1457-1973
  • Tidskriftsartikel (refereegranskat)abstract
    • These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
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  • Kersting, J., et al. (författare)
  • Effect of Radiotherapy Dose on Outcome in Nonmetastatic Sarcoma
  • 2023
  • Ingår i: Advances in Radiation Oncology. - 2452-1094. ; 8:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Radiation therapy (RT) is an integral part of Ewing sarcoma (EwS) therapy. The Ewing 2008 protocol recommended RT doses ranging from 45 to 54 Gy. However, some patients received other doses of RT. We analyzed the effect of different RT doses on event-free survival (EFS) and overall survival (OS) in patients with EwS.Methods and Materials: The Ewing 2008 database included 528 RT-admitted patients with nonmetastatic EwS. Recommended multimodal therapy consisted of multiagent chemotherapy and local treatment consisting of surgery (S & RT group) and/or RT (RT group). EFS and OS were analyzed with uni-and multivariable Cox regression models including known prognostic factors such as age, sex, tumor volume, surgical margins, and histologic response.Results: S & RT was performed in 332 patients (62.9%), and 145 patients (27.5%) received definitive RT. Standard dose =53 Gy (d1) was admitted in 57.8%, high dose of 54 to 58 Gy (d2) in 35.5%, and very high dose > 59 Gy (d3) in 6.6% of patients. In the RT group, RT dose was d1 in 11.7%, d2 in 44.1%, and d3 in 44.1% of patients. Three-year EFS in the S & RT group was 76.6% for d1, 73.7% for d2, and 68.2% for d3 (P = .42) and in the RT group 52.9%, 62.5%, and 70.3% (P = .63), respectively. Multivariable Cox regression revealed age > 15 years (hazard ratio [HR], 2.68; 95% confidence interval [CI], 1.63-4.38) and nonradical margins (HR, 1.76; 95% CI, 1.05-2.93) for the S & RT group (sex, P = .96; histologic response, P = .07; tumor volume, P = .50; dose, P = .10) and large tumor volume (HR, 2.20; 95% CI, 1.21-4.0) for the RT group as independent factors (dose, P = .15; age, P = .08; sex, P = .40).Conclusions: In the combined local therapy modality group, treatment with higher RT dose had an effect on EFS, whereas higher dose of radiation when treated with definitive RT was associated with an increased OS. Indications for selection biases for dosage were found. Upcoming trials will assess the value of different RT doses in a randomized manner to control for potential selection bias.
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  • Marina, Neyssa M., et al. (författare)
  • Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1) : an open-label, international, randomised controlled trial
  • 2016
  • Ingår i: The Lancet Oncology. - 1470-2045. ; 17:10, s. 1396-1408
  • Tidskriftsartikel (refereegranskat)abstract
    • Background We designed the EURAMOS-1 trial to investigate whether intensified postoperative chemotherapy for patients whose tumour showed a poor response to preoperative chemotherapy (≥10% viable tumour) improved event-free survival in patients with high-grade osteosarcoma. Methods EURAMOS-1 was an open-label, international, phase 3 randomised, controlled trial. Consenting patients with newly diagnosed, resectable, high-grade osteosarcoma aged 40 years or younger were eligible for randomisation. Patients were randomly assigned (1:1) to receive either postoperative cisplatin, doxorubicin, and methotrexate (MAP) or MAP plus ifosfamide and etoposide (MAPIE) using concealed permuted blocks with three stratification factors: trial group; location of tumour (proximal femur or proximal humerus vs other limb vs axial skeleton); and presence of metastases (no vs yes or possible). The MAP regimen consisted of cisplatin 120 mg/m2, doxorubicin 37·5 mg/m2 per day on days 1 and 2 (on weeks 1 and 6) followed 3 weeks later by high-dose methotrexate 12 g/m2 over 4 h. The MAPIE regimen consisted of MAP as a base regimen, with the addition of high-dose ifosfamide (14 g/m2) at 2·8 g/m2 per day with equidose mesna uroprotection, followed by etoposide 100 mg/m2 per day over 1 h on days 1–5. The primary outcome measure was event-free survival measured in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00134030. Findings Between April 14, 2005, and June 30, 2011, 2260 patients were registered from 325 sites in 17 countries. 618 patients with poor response were randomly assigned; 310 to receive MAP and 308 to receive MAPIE. Median follow-up was 62·1 months (IQR 46·6–76·6); 62·3 months (IQR 46·9–77·1) for the MAP group and 61·1 months (IQR 46·5–75·3) for the MAPIE group. 307 event-free survival events were reported (153 in the MAP group vs 154 in the MAPIE group). 193 deaths were reported (101 in the MAP group vs 92 in the MAPIE group). Event-free survival did not differ between treatment groups (hazard ratio [HR] 0·98 [95% CI 0·78–1·23]); hazards were non-proportional (p=0·0003). The most common grade 3–4 adverse events were neutropenia (268 [89%] patients in MAP vs 268 [90%] in MAPIE), thrombocytopenia (231 [78% in MAP vs 248 [83%] in MAPIE), and febrile neutropenia without documented infection (149 [50%] in MAP vs 217 [73%] in MAPIE). MAPIE was associated with more frequent grade 4 non-haematological toxicity than MAP (35 [12%] of 301 in the MAP group vs 71 [24%] of 298 in the MAPIE group). Two patients died during postoperative therapy, one from infection (although their absolute neutrophil count was normal), which was definitely related to their MAP treatment (specifically doxorubicin and cisplatin), and one from left ventricular systolic dysfunction, which was probably related to MAPIE treatment (specifically doxorubicin). One suspected unexpected serious adverse reaction was reported in the MAP group: bone marrow infarction due to methotrexate. Interpretation EURAMOS-1 results do not support the addition of ifosfamide and etoposide to postoperative chemotherapy in patients with poorly responding osteosarcoma because its administration was associated with increased toxicity without improving event-free survival. The results define standard of care for this population. New strategies are required to improve outcomes in this setting. Funding UK Medical Research Council, National Cancer Institute, European Science Foundation, St Anna Kinderkrebsforschung, Fonds National de la Recherche Scientifique, Fonds voor Wetenschappelijk Onderzoek-Vlaanderen, Parents Organization, Danish Medical Research Council, Academy of Finland, Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe, Federal Ministry of Education and Research, Semmelweis Foundation, ZonMw (Council for Medical Research), Research Council of Norway, Scandinavian Sarcoma Group, Swiss Paediatric Oncology Group, Cancer Research UK, National Institute for Health Research, University College London Hospitals, and Biomedical Research Centre.
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  • Nagaya, K., et al. (författare)
  • Formation of the energetic doubly charged ne ion by irradiation of large neon clusters using intense EUV-FEL pulses at 52 nm
  • 2010
  • Ingår i: Journal of Physics: Conference Series. - : Institute of Physics (IOP). - 1742-6596.
  • Konferensbidrag (refereegranskat)abstract
    • The interaction of clusters with intense EUV-FEL pulses was investigated using the SPring-8 Compact SASE Source (SCSS) test facility in Japan. Neon clusters of mean sizes = 1000 and 4000 were irradiated by intense FEL pulses at 52 nm and emitted ions were detected by a momentum imaging spectrometer. The production of energetic doubly charged ions was not found for Ne 1000, but it was observed for Ne 4000 clusters, which suggests that an inhomogeneous charge distribution is generated for the larger clusters.
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  • Tal, Tamara, et al. (författare)
  • New approach methods to assess developmental and adult neurotoxicity for regulatory use : a PARC work package 5 project
  • 2024
  • Ingår i: Frontiers in Toxicology. - : Frontiers Media S.A.. - 2673-3080. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • In the European regulatory context, rodent in vivo studies are the predominant source of neurotoxicity information. Although they form a cornerstone of neurotoxicological assessments, they are costly and the topic of ethical debate. While the public expects chemicals and products to be safe for the developing and mature nervous systems, considerable numbers of chemicals in commerce have not, or only to a limited extent, been assessed for their potential to cause neurotoxicity. As such, there is a societal push toward the replacement of animal models with in vitro or alternative methods. New approach methods (NAMs) can contribute to the regulatory knowledge base, increase chemical safety, and modernize chemical hazard and risk assessment. Provided they reach an acceptable level of regulatory relevance and reliability, NAMs may be considered as replacements for specific in vivo studies. The European Partnership for the Assessment of Risks from Chemicals (PARC) addresses challenges to the development and implementation of NAMs in chemical risk assessment. In collaboration with regulatory agencies, Project 5.2.1e (Neurotoxicity) aims to develop and evaluate NAMs for developmental neurotoxicity (DNT) and adult neurotoxicity (ANT) and to understand the applicability domain of specific NAMs for the detection of endocrine disruption and epigenetic perturbation. To speed up assay time and reduce costs, we identify early indicators of later-onset effects. Ultimately, we will assemble second-generation developmental neurotoxicity and first-generation adult neurotoxicity test batteries, both of which aim to provide regulatory hazard and risk assessors and industry stakeholders with robust, speedy, lower-cost, and informative next-generation hazard and risk assessment tools.
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  • Ahme, Antonia, et al. (författare)
  • Warming increases the compositional and functional variability of a temperate protist community
  • 2024
  • Ingår i: Science of the Total Environment. - 0048-9697 .- 1879-1026. ; 926
  • Tidskriftsartikel (refereegranskat)abstract
    • Phototrophic protists are a fundamental component of the world's oceans by serving as the primary source of energy, oxygen, and organic nutrients for the entire ecosystem. Due to the high thermal seasonality of their habitat, temperate protists could harbour many well-adapted species that tolerate ocean warming. However, these species may not sustain ecosystem functions equally well. To address these uncertainties, we conducted a 30-day mesocosm experiment to investigate how moderate (12 °C) and substantial (18 °C) warming compared to ambient conditions (6 °C) affect the composition (18S rRNA metabarcoding) and ecosystem functions (biomass, gross oxygen productivity, nutritional quality – C:N and C:P ratio) of a North Sea spring bloom community. Our results revealed warming-driven shifts in dominant protist groups, with haptophytes thriving at 12 °C and diatoms at 18 °C. Species responses primarily depended on the species' thermal traits, with indirect temperature effects on grazing being less relevant and phosphorus acting as a critical modulator. The species Phaeocystis globosa showed highest biomass on low phosphate concentrations and relatively increased in some replicates of both warming treatments. In line with this, the C:P ratio varied more with the presence of P. globosa than with temperature. Examining further ecosystem responses under warming, our study revealed lowered gross oxygen productivity but increased biomass accumulation whereas the C:N ratio remained unaltered. Although North Sea species exhibited resilience to elevated temperatures, a diminished functional similarity and heightened compositional variability indicate potential ecosystem repercussions for higher trophic levels. In conclusion, our research stresses the multifaceted nature of temperature effects on protist communities, emphasising the need for a holistic understanding that encompasses trait-based responses, indirect effects, and functional dynamics in the face of exacerbating temperature changes.
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  • Knight, S., et al. (författare)
  • Cavity-enhanced optical Hall effect in two-dimensional free charge carrier gases detected at terahertz frequencies
  • 2015
  • Ingår i: Optics Letters. - : Optical Society of America. - 0146-9592 .- 1539-4794. ; 40:12, s. 2688-2691
  • Tidskriftsartikel (refereegranskat)abstract
    • The effect of a tunable, externally coupled Fabry-Perot cavity to resonantly enhance the optical Hall effect signatures at terahertz frequencies produced by a traditional Drude-like two-dimensional electron gas is shown and discussed in this Letter. As a result, the detection of optical Hall effect signatures at conveniently obtainable magnetic fields, for example, by neodymium permanent magnets, is demonstrated. An AlInN/GaN-based high-electron mobility transistor structure grown on a sapphire substrate is used for the experiment. The optical Hall effect signatures and their dispersions, which are governed by the frequency and the reflectance minima and maxima of the externally coupled Fabry-Perot cavity, are presented and discussed. Tuning the externally coupled Fabry-Perot cavity strongly modifies the optical Hall effect signatures, which provides a new degree of freedom for optical Hall effect experiments in addition to frequency, angle of incidence, and magnetic field direction and strength. (C) 2015 Optical Society of America
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