Sterile neutrinos are a minimal extension of the Standard Model of Particle Physics. If their mass is in the kilo-electron-volt regime, they are viable dark matter candidates. One way to search for ...sterile neutrinos in a laboratory-based experiment is via tritium beta decay, where the new neutrino mass eigenstate would manifest itself as a kink-like distortion of the spectrum. The objective of the TRISTAN project is to extend the KATRIN setup with a novel multi-pixel silicon drift detector system to search for a keV-scale sterile neutrino signal. First seven-pixel prototype detectors were produced and characterized with radioactive X-ray and electron sources. The next prototype generation with 166 pixels is currently in production and will be available beginning of 2019. In this work, we describe the requirements of the novel TRISTAN detector system and present the technical realization of the first prototypes.
In this work we present a keV-scale sterile-neutrino search with a low-tritium-activity data set of the KATRIN experiment, acquired in a commissioning run in 2018. KATRIN performs a spectroscopic ...measurement of the tritium β-decay spectrum with the main goal of directly determining the effective electron anti-neutrino mass. During this commissioning phase a lower tritium activity facilitated the measurement of a wider part of the tritium spectrum and thus the search for sterile neutrinos with a mass of up to 1.6 keV. We do not find a signal and set an exclusion limit on the sterile-to-active mixing amplitude of $\text {sin}^{2}\: \theta<5\times 10^{-4}\: (95\%\: $C.L) at a mass of 0.3 keV. This result improves current laboratory-based bounds in the sterile-neutrino mass range between 0.1 and 1.0 keV.
Because of the pronounced radioresistance of glioblastoma multiforme the prognosis of this disease remains poor. Therefore, we investigated the impact of an additional simultaneous chemotherapy with ...the topoisomerase-I inhibitor topotecan (Hycamtin) on the quality of life and toxicity of radiotherapy.
In this multicenter trial patients with histologically proven glioblastoma multiforme underwent a simultaneous radio-chemotherapy. Including pilot phase 60 patients, 41 male and 19 female, were treated. Age ranged from 26 to 76 years, the mean was 57 years. Conventional fractionated conformal radiotherapy was performed with daily doses of 2.0 Gy to a total dose of 60 Gy. 1 hour prior to irradiation 0.5 mg (absolute dose) of topotecan were administered intravenously resulting in a cumulative dose of 15 mg. Besides hematologic and non-hematologic toxicity, quality of life was assessed by Karnofsky index and Spitzer index. Additionally local control and survival time were recorded.
57 patients completed the combined therapy. Median administered dose of radiation was 60 Gy (16-76 Gy). Median cumulative topotecan dose was 15 mg (7.5-18.5 mg). Grade-III toxicity was found in six cases (two hematologic, two motoric disorder, one infection, one nausea) and grade-IV toxicity in three cases (one esophagitis, one motoric disorder, one mental disorder). Two patients died of septic disease most likely caused by steroid induced immunosuppression. Mean Karnofsky index and Spitzer index initially, at the end of therapy and 6 weeks after therapy showed values of 87%, 81% and 80% and 19 points, 18 points and 19 points, respectively. Median survival time was 15 months.
This multimodal approach for patients with glioblastoma multiforme is well tolerated. Quality of life remains preserved and outpatient treatment is possible. The relatively long median survival time even for patients bearing macroscopic tumors is promising.
The KArlsruhe TRItium Neutrino experiment (KATRIN) aims to determine the effective electron (anti)-neutrino mass with a sensitivity of 0.2eV/c \(^2\) by precisely measuring the endpoint region of the ...tritium \(\beta \) -decay spectrum. It uses a tandem of electrostatic spectrometers working as magnetic adiabatic collimation combined with an electrostatic (MAC-E) filters. In the space between the pre-spectrometer and the main spectrometer, creating a Penning trap is unavoidable when the superconducting magnet between the two spectrometers, biased at their respective nominal potentials, is energized. The electrons accumulated in this trap can lead to discharges, which create additional background electrons and endanger the spectrometer and detector section downstream. To counteract this problem, “electron catchers” were installed in the beamline inside the magnet bore between the two spectrometers. These catchers can be moved across the magnetic-flux tube and intercept on a sub-ms time scale the stored electrons along their magnetron motion paths. In this paper, we report on the design and the successful commissioning of the electron catchers and present results on their efficiency in reducing the experimental background.
Due to its radioresistance, the prognosis of glioblastoma multiforme (GBM) remains poor. Therefore, we investigated the impact of simultaneous radio-chemotherapy with topotecan (Hycamtin
®) on ...clinical outcome, tolerability and quality of life.
In this multicenter trial, 60 patients (19 females, 41 males) with histologically proven (5× biopsy, 31× subtotal resection, 24× total resection) GBM were included. Radio-Chemotherapy was performed with daily doses of 2.0
Gy (total, 60
Gy), and 0.5
mg (absolute dose) of topotecan intravenously 1
h prior to irradiation. Toxicity was assessed using common toxicity criteria (CTC). General condition and quality of life were assessed at baseline, at the end of therapy, and 6 weeks post-therapy. Local control and length of survival were compared with an historical control group of 67 patients only treated with postoperative radiotherapy following stereotactic biopsy (15×), subtotal resection (39×), or total resection (13×).
57 patients completed the therapy. Median radiation dose was 60
Gy (range 16–76
Gy). Median cumulative topotecan dose was 15
mg (range 7.5–18.5
mg). CTC toxicity grade 3 was observed in six patients and grade 4 toxicity in two patients (three events). Two patients died of septic disease. Mean Karnofsky index was 87% at baseline, 81% at the end of therapy, and 80% at 6 weeks post-therapy. Median survival time was 15 months, significantly longer than the 11 months seen in the control group (
P < 0.002). Extent of tumour resection or patient age did not have a significant effect on survival.
This multimodal approach is well tolerated, and quality of life remains preserved. The relatively long median survival time is promising but a further randomised double blind placebo controlled parallel designed clinical trial should be performed to confirm these results.
Liposomes containing phosphatidic acid were capable of stimulating DNA synthesis in quiescent Swiss 3T3 cells while liposomes composed of other phospholipids were not. These results show that ...liposomes, which are usually employed to deliver non-lipid molecules into cells, can themselves have profound effects on cell growth. The possible mechanism of phosphatidic acid-mediated cell stimulation and its relation to other growth factors are discussed.
The ARO 96-02 trial primarily compared wait-and-see (WS, arm A) with adjuvant radiation therapy (ART, arm B) in prostate cancer patients who achieved an undetectable prostate-specific antigen (PSA) ...after radical prostatectomy (RP). Here, we report the outcome with up to 12 years of follow-up of patients who retained a post-RP detectable PSA and received salvage radiation therapy (SRT, arm C).
For the study, 388 patients with pT3-4pN0 prostate cancer with positive or negative surgical margins were recruited. After RP, 307 men achieved an undetectable PSA (arms A + B). In 78 patients the PSA remained above thresholds (median 0.6, range 0.05-5.6 ng/mL). Of the latter, 74 consented to receive 66 Gy to the prostate bed, and SRT was applied at a median of 86 days after RP. Clinical relapse-free survival, metastasis-free survival, and overall survival were determined by the Kaplan-Meier method.
Patients with persisting PSA after RP had higher preoperative PSA values, higher tumor stages, higher Gleason scores, and more positive surgical margins than did patients in arms A + B. For the 74 patients, the 10-year clinical relapse-free survival rate was 63%. Forty-three men had hormone therapy; 12 experienced distant metastases; 23 patients died. Compared with men who did achieve an undetectable PSA, the arm-C patients fared significantly worse, with a 10-year metastasis-free survival of 67% versus 83% and overall survival of 68% versus 84%, respectively. In Cox regression analysis, Gleason score ≥8 (hazard ratio HR 2.8), pT ≥ 3c (HR 2.4), and extraprostatic extension ≥2 mm (HR 3.6) were unfavorable risk factors of progression.
A persisting PSA after prostatectomy seems to be an important prognosticator of clinical progression for pT3 tumors. It correlates with a higher rate of distant metastases and with worse overall survival. A larger prospective study is required to determine which patient subgroups will benefit most from which treatment option.
The fact that neutrinos carry a non-vanishing rest mass is evidence of physics beyond the Standard Model of elementary particles. Their absolute mass bears important relevance from particle physics ...to cosmology. In this work, we report on the search for the effective electron antineutrino mass with the KATRIN experiment. KATRIN performs precision spectroscopy of the tritium \(\beta\)-decay close to the kinematic endpoint. Based on the first five neutrino-mass measurement campaigns, we derive a best-fit value of \(m_\nu^{2} = {-0.14^{+0.13}_{-0.15}}~\mathrm{eV^2}\), resulting in an upper limit of \(m_\nu < {0.45}~\mathrm{eV}\) at 90 % confidence level. With six times the statistics of previous data sets, amounting to 36 million electrons collected in 259 measurement days, a substantial reduction of the background level and improved systematic uncertainties, this result tightens KATRIN's previous bound by a factor of almost two.
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