University of Tübingen

About: University of Tübingen is a education organization based out in Tübingen, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 40555 authors who have published 84108 publications receiving 3015320 citations. The organization is also known as: Eberhard Karls University & Eberhard-Karls-Universität Tübingen.

Magnetic phase control by an electric field

Abstract: The quest for higher data density in information storage is motivating investigations into approaches for manipulating magnetization by means other than magnetic fields. This is evidenced by the recent boom in magnetoelectronics and 'spintronics', where phenomena such as carrier effects in magnetic semiconductors and high-correlation effects in colossal magnetoresistive compounds are studied for their device potential. The linear magnetoelectric effect-the induction of polarization by a magnetic field and of magnetization by an electric field-provides another route for linking magnetic and electric properties. It was recently discovered that composite materials and magnetic ferroelectrics exhibit magnetoelectric effects that exceed previously known effects by orders of magnitude, with the potential to trigger magnetic or electric phase transitions. Here we report a system whose magnetic phase can be controlled by an external electric field: ferromagnetic ordering in hexagonal HoMnO3 is reversibly switched on and off by the applied field via magnetoelectric interactions. We monitor this process using magneto-optical techniques and reveal its microscopic origin by neutron and X-ray diffraction. From our results, we identify basic requirements for other candidate materials to exhibit magnetoelectric phase control.

Safety and efficacy of vemurafenib in BRAFV600E and BRAFV600K mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study

Abstract: Summary Background In the BRIM-3 trial, vemurafenib was associated with risk reduction versus dacarbazine of both death and progression in patients with advanced BRAF V600 mutation-positive melanoma. We present an extended follow-up analysis of the total population and in the BRAF V600E and BRAF V600K mutation subgroups. Methods Patients older than 18 years, with treatment-naive metastatic melanoma and whose tumour tissue was positive for BRAF V600 mutations were eligible. Patients also had to have a life expectancy of at least 3 months, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate haematological, hepatic, and renal function. Patients were randomly assigned by interactive voice recognition system to receive either vemurafenib (960 mg orally twice daily) or dacarbazine (1000 mg/m 2 of body surface area intravenously every 3 weeks). Coprimary endpoints were overall survival and progression-free survival, analysed in the intention-to-treat population (n=675), with data censored at crossover. A sensitivity analysis was done. This trial is registered with ClinicalTrials.gov, NCT01006980. Findings 675 eligible patients were enrolled from 104 centres in 12 countries between Jan 4, 2010, and Dec 16, 2010. 337 patients were randomly assigned to receive vemurafenib and 338 to receive dacarbazine. Median follow-up was 12·5 months (IQR 7·7–16·0) on vemurafenib and 9·5 months (3·1–14·7) on dacarbazine. 83 (25%) of the 338 patients initially randomly assigned to dacarbazine crossed over from dacarbazine to vemurafenib. Median overall survival was significantly longer in the vemurafenib group than in the dacarbazine group (13·6 months [95% CI 12·0–15·2] vs 9·7 months [7·9–12·8]; hazard ratio [HR] 0·70 [95% CI 0·57–0·87]; p=0·0008), as was median progression-free survival (6·9 months [95% CI 6·1–7·0] vs 1·6 months [1·6–2·1]; HR 0·38 [95% CI 0·32–0·46]; p BRAF V600E disease, median overall survival in the vemurafenib group was 13·3 months (95% CI 11·9–14·9) compared with 10·0 months (8·0–14·0) in the dacarbazine group (HR 0·75 [95% CI 0·60–0·93]; p=0·0085); median progression-free survival was 6·9 months (95% CI 6·2–7·0) and 1·6 months (1·6–2·1), respectively (HR 0·39 [95% CI 0·33–0·47]; p BRAF V600K disease, median overall survival in the vemurafenib group was 14·5 months (95% CI 11·2–not estimable) compared with 7·6 months (6·1–16·6) in the dacarbazine group (HR 0·43 [95% CI 0·21–0·90]; p=0·024); median progression-free survival was 5·9 months (95% CI 4·4–9·0) and 1·7 months (1·4–2·9), respectively (HR 0·30 [95% CI 0·16–0·56]; p Interpretation Inhibition of BRAF with vemurafenib improves survival in patients with the most common BRAF V600E mutation and in patients with the less common BRAF V600K mutation. Funding F Hoffmann-La Roche-Genentech.

Local delivery of paclitaxel to inhibit restenosis during angioplasty of the leg.

Abstract: A b s t r ac t BACKGROUND Drug-eluting stents reduce restenosis in coronary arteries, but clinical trials have failed to prove their efficacy in peripheral arteries. We investigated the use of paclitaxel-coated angioplasty balloons and paclitaxel dissolved in the angiographic contrast medium during angioplasty of the leg. METHODS In a small, multicenter trial, we randomly assigned 154 patients with stenosis or occlusion of a femoropopliteal artery to treatment with standard balloon catheters coated with paclitaxel, uncoated balloons with paclitaxel dissolved in the contrast medium, or uncoated balloons without paclitaxel (control). The primary end point was late lumen loss at 6 months. RESULTS The mean (±SD) age of the patients was 68±8 years, 24% were smokers, and 49% had diabetes. Twenty-seven percent of the lesions were total occlusions, and 36% were restenotic lesions. The mean lesion length was 7.4±6.5 cm. There were no significant differences in baseline characteristics between the groups. There were no adverse events attributable to the paclitaxel-coated balloons. At 6 months, the mean late lumen loss was 1.7±1.8 mm in the control group, as compared with 0.4±1.2 mm (P<0.001) in the group treated with paclitaxel-coated balloons and 2.2±1.6 mm (P = 0.11) in the group treated with paclitaxel in the contrast medium. The rate of revascularization of target lesions at 6 months was 20 of 54 (37%) in the control group, 2 of 48 (4%) in the group treated with paclitaxel-coated balloons (P<0.001 vs. control), and 15 of 52 (29%) in the group treated with paclitaxel in the contrast medium (P = 0.41 vs. control); at 24 months, the rates increased to 28 of 54 (52%), 7 of 48 (15%), and 21 of 52 (40%), respectively. CONCLUSIONS Use of paclitaxel-coated angioplasty balloons during percutaneous treatment of femoropopliteal disease is associated with significant reductions in late lumen loss and target-lesion revascularization. No significant benefit is seen with the use of a paclitaxel-containing contrast medium. (ClinicalTrials.gov number, NCT00156624.)

Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial

Abstract: Summary Background Effective targeted treatment is unavailable for most sarcomas and doxorubicin and ifosfamide—which have been used to treat soft-tissue sarcoma for more than 30 years—still have an important role Whether doxorubicin alone or the combination of doxorubicin and ifosfamide should be used routinely is still controversial We assessed whether dose intensification of doxorubicin with ifosfamide improves survival of patients with advanced soft-tissue sarcoma compared with doxorubicin alone Methods We did this phase 3 randomised controlled trial (EORTC 62012) at 38 hospitals in ten countries We included patients with locally advanced, unresectable, or metastatic high-grade soft-tissue sarcoma, age 18–60 years with a WHO performance status of 0 or 1 They were randomly assigned (1:1) by the minimisation method to either doxorubicin (75 mg/m 2 by intravenous bolus on day 1 or 72 h continuous intravenous infusion) or intensified doxorubicin (75 mg/m 2 ; 25 mg/m 2 per day, days 1–3) plus ifosfamide (10 g/m 2 over 4 days with mesna and pegfilgrastim) as first-line treatment Randomisation was stratified by centre, performance status (0 vs 1), age ( vs ≥50 years), presence of liver metastases, and histopathological grade (2 vs 3) Patients were treated every 3 weeks till progression or unacceptable toxic effects for up to six cycles The primary endpoint was overall survival in the intention-to-treat population The trial is registered with ClinicalTrialsgov, number NCT00061984 Findings Between April 30, 2003, and May 25, 2010, 228 patients were randomly assigned to receive doxorubicin and 227 to receive doxorubicin and ifosfamide Median follow-up was 56 months (IQR 31–77) in the doxorubicin only group and 59 months (36–72) in the combination group There was no significant difference in overall survival between groups (median overall survival 12·8 months [95·5% CI 10·5–14·3] in the doxorubicin group vs 14·3 months [12·5–16·5] in the doxorubicin and ifosfamide group; hazard ratio [HR] 0·83 [95·5% CI 0·67–1·03]; stratified log-rank test p=0·076) Median progression-free survival was significantly higher for the doxorubicin and ifosfamide group (7·4 months [95% CI 6·6–8·3]) than for the doxorubicin group (4·6 months [2·9–5·6]; HR 0·74 [95% CI 0·60–0·90], stratified log-rank test p=0·003) More patients in the doxorubicin and ifosfamide group than in the doxorubicin group had an overall response (60 [26%] of 227 patients vs 31 [14%] of 228; p vs 40 [18%] of 223 patients), neutropenia (93 [42%] vs 83 [37%]), febrile neutropenia (103 (46%) vs 30 [13%]), anaemia (78 [35%] vs 10 [5%]), and thrombocytopenia (75 [33%]) vs one [ Interpretation Our results do not support the use of intensified doxorubicin and ifosfamide for palliation of advanced soft-tissue sarcoma unless the specific goal is tumour shrinkage These findings should help individualise the care of patients with this disease Funding Cancer Research UK, EORTC Charitable Trust, UK NHS, Canadian Cancer Society Research Institute, Amgen