| 1. |
- Cossarizza, A., et al.
(författare)
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Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
- 2019
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Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 49:10, s. 1457-1973
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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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| 2. |
- Persson, P. O.Å., et al.
(författare)
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Tuning composition in graded AlGaN channel HEMTs toward improved linearity for low-noise radio-frequency amplifiers
- 2023
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 122:15
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Tidskriftsartikel (refereegranskat)abstract
- Compositionally graded channel AlGaN/GaN high electron mobility transistors (HEMTs) offer a promising route to improve device linearity, which is necessary for low-noise radio-frequency amplifiers. In this work, we demonstrate different grading profiles of a 10-nm-thick AlxGa1-xN channel from x = 0 to x = 0.1 using hot-wall metal-organic chemical vapor deposition (MOCVD). The growth process is developed by optimizing the channel grading and the channel-to-barrier transition. For this purpose, the Al-profiles and the interface sharpness, as determined from scanning transmission electron microscopy combined with energy-dispersive x-ray spectroscopy, are correlated with specific MOCVD process parameters. The results are linked to the channel properties (electron density, electron mobility, and sheet resistance) obtained by contactless Hall and terahertz optical Hall effect measurements coupled with simulations from solving self-consistently Poisson and Schrödinger equations. The impact of incorporating a thin AlN interlayer between the graded channel and the barrier layer on the HEMT properties is investigated and discussed. The optimized graded channel HEMT structure is found to have similarly high electron density (∼9 × 10 12 cm-2) as the non-graded conventional structure, though the mobility drops from ∼ 2360 cm2/V s in the conventional to ∼ 960 cm2/V s in the graded structure. The transconductance gm of the linearly graded channel HEMTs is shown to be flatter with smaller g m ′ and g m ″ as compared to the conventional non-graded channel HEMT implying improved device linearity.
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| 3. |
- Kersting, J., et al.
(författare)
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Effect of Radiotherapy Dose on Outcome in Nonmetastatic Sarcoma
- 2023
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Ingår i: Advances in Radiation Oncology. ; 8:4
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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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| 4. |
- Knoebl, P, et al.
(författare)
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Demographic and clinical data in acquired hemophilia a: results from the european acquired haemophilia (each2) registry.
- 2012
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 10:4, s. 622-631
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Tidskriftsartikel (refereegranskat)abstract
- Background: Acquired hemophilia A (AHA) is a rare autoimmune disease caused by autoantibodies against coagulation factor VIII and characterized by spontaneous hemorrhage in patients with no previous family or personal history of bleeding. Although data on several AHA cohorts have been collected, limited information is available on the optimal management of AHA. Objectives: The European Acquired Hemophilia registry (EACH2) was established to generate a prospective, large-scale, pan-European database on demographics, diagnosis, underlying disorders, bleeding characteristics, treatment and outcome of AHA patients. Results: 501 (266 male, 235 female) patients from 117 centers and 13 European countries were included in the registry between 2003-2008. In 467 cases, hemostasis investigations and AHA diagnosis were triggered by a bleeding event. At diagnosis, patients were a median of 73.9 years. AHA was idiopathic in 51.9%; malignancy or autoimmune diseases were associated with 11.8% and 11.6% of cases. 57% of the non-pregnancy-related cases were male. 474 bleeding episodes were reported at presentation, and hemostatic therapy initiated in 70.5% of patients. Delayed diagnosis significantly impacted treatment initiation in 33.5%. 477 patients underwent immunosuppression, and 72.6% achieved complete remission. Conclusions: Representing the largest collection of consecutive AHA cases to date, EACH2 facilitates the analysis of a variety of open questions in AHA.
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| 5. |
- Tengborn, Lilian, et al.
(författare)
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Pregnancy-associated acquired haemophilia A: results from the European Acquired Haemophilia (EACH2) registry.
- 2012
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Ingår i: BJOG: An International Journal of Obstetrics & Gynaecology. - : Wiley. - 1471-0528 .- 1470-0328. ; 119:12, s. 1529-1537
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The European Acquired Haemophilia registry (EACH2) collected data on the demographics, diagnosis, underlying disorders, bleeding characteristics, treatment, and outcome of women with acquired haemophilia A (AHA), a rare and often severe bleeding disorder caused by autoantibodies directed against coagulation factor VIII. Design: Prospective, multi-centre, large-scale, pan-European registry. Setting A total of 117 haemophilia centres in 13 European countries. Population Pregnancy-associated AHA. Methods Data were reported using a web-based electronic case report form. Diagnosis was based on the presence of a prolonged activated partial thromboplastin time, reduced coagulation Factor VIII level and positive inhibitor assay. Main outcome measures: Presenting characteristics, time to diagnosis, haemostatic treatment and outcome, immunosuppressive treatment and outcome. Results The EACH2 registry (n = 501) documented 42 (8.4%) cases of AHA associated with the peripartum period, a median Factor VIII level at diagnosis of 2.5 (range 0-25) IU/dl and inhibitor titre of 7.8 (range 0.7-348) BU/ml. Antepartum inhibitors were evident in eight women. Time to diagnosis of AHA after delivery was 89 (range 21-120) days. First-line haemostatic treatment was successful in 20/23 (87%) women treated. Bleeding episodes resolved in 17/18 (94%) women treated with a bypassing agent and 29/39 (74%) women achieved complete remission with first-line immunosuppressive treatment. Two babies experienced postnatal bleeding, suggesting transplacental transfer of the antibody. All women were alive at last follow-up. Conclusions: Although rare, pregnancy-associated AHA may cause severe bleeding-related morbidity. Once diagnosed, women respond well to haemostatic treatment with bypassing agents and immunosuppression. Awareness of peripartum AHA requires improvement to facilitate rapid and appropriate management.
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| 6. |
- Bréchignac, Francois, et al.
(författare)
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Addressing ecological effects of radiation on populations and ecosystems to improve protection of the environment against radiation : Agreed statements from a Consensus Symposium
- 2016
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Ingår i: Journal of Environmental Radioactivity. - : Elsevier BV. - 0265-931X .- 1879-1700. ; 158, s. 21-29
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Forskningsöversikt (refereegranskat)abstract
- This paper reports the output of a consensus symposium organized by the International Union of Radioecology in November 2015. The symposium gathered an academically diverse group of 30 scientists to consider the still debated ecological impact of radiation on populations and ecosystems. Stimulated by the Chernobyl and Fukushima disasters' accidental contamination of the environment, there is increasing interest in developing environmental radiation protection frameworks. Scientific research conducted in a variety of laboratory and field settings has improved our knowledge of the effects of ionizing radiation on the environment. However, the results from such studies sometimes appear contradictory and there is disagreement about the implications for risk assessment. The Symposium discussions therefore focused on issues that might lead to different interpretations of the results, such as laboratory versus field approaches, organism versus population and ecosystemic inference strategies, dose estimation approaches and their significance under chronic exposure conditions. The participating scientists, from across the spectrum of disciplines and research areas, extending also beyond the traditional radioecology community, successfully developed a constructive spirit directed at understanding discrepancies. From the discussions, the group has derived seven consensus statements related to environmental protection against radiation, which are supplemented with some recommendations. Each of these statements is contextualized and discussed in view of contributing to the orientation and integration of future research, the results of which should yield better consensus on the ecological impact of radiation and consolidate suitable approaches for efficient radiological protection of the environment.
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| 7. |
- Knight, Sean Robert, et al.
(författare)
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Room temperature two-dimensional electron gas scattering time, effective mass, and mobility parameters in AlxGa1−xN/GaN heterostructures (0.07 ≤ x ≤ 0.42)
- 2023
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Ingår i: Journal of Applied Physics. - : American Institute of Physics Inc.. - 0021-8979 .- 1089-7550. ; 134:18
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Tidskriftsartikel (refereegranskat)abstract
- Al xGa 1−xN/GaN high-electron-mobility transistor (HEMT) structures are key components in electronic devices operating at gigahertz or higher frequencies. In order to optimize such HEMT structures, understanding their electronic response at high frequencies and room temperature is required. Here, we present a study of the room temperature free charge carrier properties of the two-dimensional electron gas (2DEG) in HEMT structures with varying Al content in the Al xGa 1−xN barrier layers between x=0.07 and x=0.42. We discuss and compare 2DEG sheet density, mobility, effective mass, sheet resistance, and scattering times, which are determined by theoretical calculations, contactless Hall effect, capacitance-voltage, Eddy current, and cavity-enhanced terahertz optical Hall effect (THz-OHE) measurements using a low-field permanent magnet (0.6 T). From our THz-OHE results, we observe that the measured mobility reduction from x=0.13 to x=0.42 is driven by the decrease in 2DEG scattering time, and not the change in effective mass. For x<0.42, the 2DEG effective mass is found to be larger than for electrons in bulk GaN, which in turn, contributes to a decrease in the principally achievable mobility. From our theoretical calculations, we find that values close to 0.3 m0 can be explained by the combined effects of conduction band nonparabolicity, polarons, and hybridization of the electron wavefunction through penetration into the barrier layer.
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| 8. |
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| 9. |
- Marina, Neyssa M., et al.
(författare)
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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
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Ingår i: The Lancet Oncology. - 1470-2045. ; 17:10, s. 1396-1408
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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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| 10. |
- Moschovitis, Giorgio, et al.
(författare)
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Heart rate and adverse outcomes in patients with prevalent atrial fibrillation
- 2021
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Ingår i: Open Heart. - : BMJ. - 2053-3624. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The optimal target heart rate in patients with prevalent atrial fibrillation (AF) is not well defined. The aim of this study was to analyse the associations between heart rate and adverse outcomes in a large contemporary cohort of patients with prevalent AF.METHODS: From two prospective cohort studies, we included stable AF outpatients who were in AF on the baseline ECG. The main outcome events assessed during prospective follow-up were heart failure hospitalisation, stroke or systemic embolism and death. The associations between heart rate and adverse outcomes were evaluated using multivariable Cox regression models.RESULTS: The study population consisted of 1679 patients who had prevalent AF at baseline. Mean age was 74 years, and 24.6% were women. The mean heart rate on the baseline ECG was 78 (±19) beats per minute (bpm). The median follow-up was 3.9 years (IQR 2.2-5.0). Heart rate was not significantly associated with heart failure hospitalisation (adjusted HR (aHR) per 10 bpm increase, 1.00, 95% CI 0.94 to 1.07, p=0.95), stroke or systemic embolism (aHR 0.95, 95% CI 0.84 to 1.07, p=0.38) or death (aHR 1.02, 95% CI 0.95 to 1.09, p=0.66). There was no evidence of a threshold effect for heart rates <60 bpm or >100 bpm.CONCLUSIONS: In this large contemporary cohort of outpatients with prevalent AF, we found no association between heart rate and adverse outcome events. These data are in line with recommendations that strict heart rate control is not needed in otherwise stable outpatients with AF.
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