Imaging Performance of the XMM-Newton X-ray telescopes

The in-orbit imaging performance of the three X-ray telescopes on board of the X-ray astronomy observatory XMM-Newton is presented and compared with the performance measured on ground at the MPE PANTER test facility. The comparison shows an excellent agreement between the on ground and in-orbit performance.Comment: 9 pages, 10 Postscript figures, for SPIE 4012, paper 8

Strategies for Nitrogen Fertilization of Winter Wheat Using Ammonium Stabilized Fertilizers. 2. Effects on Yield Components and Grain Quality

In einer Versuchsserie von 1999 bis 2003 wurde der Einsatz von stabilisiertem Stickstoff bei unterschiedlicher Verteilung geprüft. Ausgehend von dem konventionellen N-Düngesystem mit bis zu vier Teilgaben wurden beim Einsatz von stabilisiertem Ammonsulfatsalpeter (ASS) jeweils zwei N-Gaben zu Vegetationsbeginn bzw. zum Schossen zusammengelegt. Der Winterweizen reagierte positiv auf ein System mit einer geringen Andüngung von bis 60 kg N ha-1 als Kalkammonsalpeter (KAS), gefolgt von einer schosser-betonten N-Gabe von ca. 120 kg N ha-1 als stabilisierter ASS. Folgende Ergebnisse wurden erzielt: 1. Der Mehrertrag von 3,3 dt ha-1 gegenüber der Standarddüngung ergab sich aus einem höheren Kornansatz von etwa drei Körnern pro Ähre. Bestandesdichte und TKG wiesen keine signifikanten Unterschiede in den Düngungsvarianten auf. 2. Der Rohproteingehalt wurde durch das Vorziehen der Spätdüngung auf das Schossen (ES 30/32) nicht negativ beeinflusst. Er lag auf gleichem Niveau wie nach dem Standard-Düngesystem, konnte aber durch eine zusätzliche N-Gabe von 40 kg N ha-1 zum ES 49 um 0,8%-Punkte angehoben werden. 3. Das schosser-betonte N-System mit stabilisiertem Stickstoff führte im Vergleich zum konventionellen Düngesystem zu einer erhöhten N-Konzentration im Aufwuchs während der Schossphase und zu einer Vergrößerung der Fläche des Fahnenblattes um 12%.From 1999 to 2003 field trials have been conducted at different sites in Germany in order to develop a fertilization system with stabilized ammonium sulphate nitrate (ASN) compared to a standard application with ammonium nitrate containing fertilizers (CAN). The tested N stabilizer was the nitrification inhibitor 3, 4-dimethylpyrazole phosphate. The yield response of winter wheat to a combined application of 60 kg N ha-1 as CAN at beginning of vegetation in spring and 120 kg N ha-1 as stabilized ASN at growth stage 30/32 was positive. Following effects were found: 1. The yield increase of 0.33 t ha-1 derived from a better grain set by nearly 3 grains per ear. Ear density and thousand kernel weight were not affected by the fertilization systems. 2. The content of crude protein has not been altered by the different distribution of fertilizer nitrogen. An additional N application of 40 kg N ha-1 at growth stage 49 applied after 60+120 kg N ha-1, however, led to a significantly higher crude protein content (+0.8% absolute). 3. The application of 120 kg N ha-1 as ASN stabilized nitrogen at growth stage 30/32 induced a higher N concentration in green shoots during stem elongation and 12% larger area of flag leaf

Amino-acid PET versus MRI guided re-irradiation in patients with recurrent glioblastoma multiforme (GLIAA) – protocol of a randomized phase II trial (NOA 10/ARO 2013-1)

Background: The higher specificity of amino-acid positron emission tomography (AA-PET) in the diagnosis of gliomas, as well as in the differentiation between recurrence and treatment-related alterations, in comparison to contrast enhancement in T1-weighted MRI was demonstrated in many studies and is the rationale for their implementation into radiation oncology treatment planning. Several clinical trials have demonstrated the significant differences between AA-PET and standard MRI concerning the definition of the gross tumor volume (GTV). A small single-center non-randomized prospective study in patients with recurrent high grade gliomas treated with stereotactic fractionated radiotherapy (SFRT) showed a significant improvement in survival when AA-PET was integrated in target volume delineation, in comparison to patients treated based on CT/MRI alone. Methods: This protocol describes a prospective, open label, randomized, multi-center phase II trial designed to test if radiotherapy target volume delineation based on FET-PET leads to improvement in progression free survival (PFS) in patients with recurrent glioblastoma (GBM) treated with re-irradiation, compared to target volume delineation based on T1Gd-MRI. The target sample size is 200 randomized patients with a 1:1 allocation ratio to both arms. The primary endpoint (PFS) is determined by serial MRI scans, supplemented by AA-PET-scans and/or biopsy/surgery if suspicious of progression. Secondary endpoints include overall survival (OS), locally controlled survival (time to local progression or death), volumetric assessment of GTV delineated by either method, topography of progression in relation to MRIor PET-derived target volumes, rate of long term survivors (> 1 year), localization of necrosis after re-irradiation, quality of life (QoL) assessed by the EORTC QLQ-C15 PAL questionnaire, evaluation of safety of FET-application in AA-PET imaging and toxicity of re-irradiation. Discussion: This is a protocol of a randomized phase II trial designed to test a new strategy of radiotherapy target volume delineation for improving the outcome of patients with recurrent GBM. Moreover, the trial will help to develop a standardized methodology for the integration of AA-PET and other imaging biomarkers in radiation treatment planning. Trial registration: The GLIAA trial is registered with ClinicalTrials.gov (NCT01252459, registration date 02.12.2010), German Clinical Trials Registry (DRKS00000634, registration date 10.10.2014), and European Clinical Trials Database (EudraCT-No. 2012-001121-27, registration date 27.02.2012)

Hypofractionated stereotactic re-irradiation: treatment option in recurrent malignant glioma

BACKGROUND: Hypofractionated stereotactic radiotherapy (HFSRT) is one salvage treatment option in previously irradiated patients with recurrent malignant glioma. We analyzed the results of HFSRT and prognostic factors in a single-institution series. METHODS: Between 1997 and 2003, 19 patients with recurrent malignant glioma (14 glioblastoma on most recent histology, 5 anaplastic astrocytoma) were treated with HFSRT. The median interval from post-operative radiotherapy to HFSRT was 19 (range 3–116) months, the median daily single dose 5 (4–10) Gy, the median total dose 30 (20–30) Gy and the median planning target volume 15 (4–70) ml. RESULTS: The median overall survival (OS) was 9.3 (1.9-77.6+) months from the time of HFSRT, 15.4 months for grade III and 7.9 months for grade IV tumors (p = 0.029, log-rank test). Two patients were alive at 34.6 and 77.6 months. OS was longer after a total dose of 30 Gy (11.1 months) than after total doses of <30 Gy (7.4 months; p = 0.051). Of five (26%) reoperations, none was performed for presumed or histologically predominant radiation necrosis. Median time to tumor progression after HFSRT on imaging was 4.9 months (1.3 to 37.3) months. CONCLUSION: HFSRT with conservative total doses of no more than 30 Gy is safe and leads to similar OS times as more aggressive treatment schemes. In individual patients, HFSRT in combination with other salvage treatment modalities, was associated with long-term survival

Radiation-hypersensitive cancer patients do not manifest protein expression abnormalities in components of the nonhomologous end-joining (NHEJ) pathway

Radiation therapy (RT) is utilised for the treatment of around half of all oncology patients during the course of their illness. Despite great clinical progress in the rational deployment of RT, the underlying molecular basis for its efficacy and toxicity are currently imperfectly understood. In this study, we took a biochemical approach to evaluate the potential role of key ionising radiation repair proteins in the treatment outcomes of patients with severe acute or late RT side effects. Lymphoblastoid cell lines were established from blood samples from 36 radiosensitive cases and a number of controls (the latter had had RT but did not develop significant toxicity). The expression level and migration of key proteins from the nonhomologous end-joining (NHEJ) pathway was evaluated by Western blot analysis on cases and controls. We did not observe any abnormalities in expression level or migration pattern of the following NHEJ proteins in radiosensitive cancer cases: Ku70, Ku80, XRCC4, DNA Ligase IV. These important negative results provide evidence that mutations that affect protein expression of these NHEJ components are unlikely to underlie clinical radiation sensitivity

Genetics of intellectual disability in consanguineous families

Autosomal recessive (AR) gene defects are the leading genetic cause of intellectual disability (ID) in countries with frequent parental consanguinity, which account for about 1/7th of the world population. Yet, compared to autosomal dominant de novo mutations, which are the predominant cause of ID in Western countries, the identification of AR-ID genes has lagged behind. Here, we report on whole exome and whole genome sequencing in 404 consanguineous predominantly Iranian families with two or more affected offspring. In 219 of these, we found likely causative variants, involving 77 known and 77 novel AR-ID (candidate) genes, 21 X-linked genes, as well as 9 genes previously implicated in diseases other than ID. This study, the largest of its kind published to date, illustrates that high-throughput DNA sequencing in consanguineous families is a superior strategy for elucidating the thousands of hitherto unknown gene defects underlying AR-ID, and it sheds light on their prevalence

Radiosensitivity in breast cancer assessed by the Comet and micronucleus assays

Spontaneous and radiation-induced genetic instability of peripheral blood mononuclear cells derived from unselected breast cancer (BC) patients (n=50) was examined using the single-cell gel electrophoresis (Comet) assay and a modified G2 micronucleus (MN) test. Cells from apparently healthy donors (n=16) and from cancer patients (n=9) with an adverse early skin reaction to radiotherapy (RT) served as references. Nonirradiated cells from the three tested groups exhibited similar baseline levels of DNA fragmentation assessed by the Comet assay. Likewise, the Comet analysis of in vitro irradiated (5 Gy) cells did not reveal any significant differences among the three groups with respect to the initial and residual DNA fragmentation, as well as the DNA repair kinetics. The G2 MN test showed that cells from cancer patients with an adverse skin reaction to RT displayed increased frequencies of both spontaneous and radiation-induced MN compared to healthy control or the group of unselected BC patients. Two patients from the latter group developed an increased early skin reaction to RT, which was associated with an increased initial DNA fragmentation in vitro only in one of them. Cells from the other BC patient exhibited a striking slope in the dose–response curve detected by the G2 MN test. We also found that previous RT strongly increased both spontaneous and in vitro radiation-induced MN levels, and to a lesser extent, the radiation-induced DNA damage assessed by the Comet assay. These data suggest that clinical radiation may provoke genetic instability and/or induce persistent DNA damage in normal cells of cancer patients, thus leading to increased levels of MN induction and DNA fragmentation after irradiation in vitro. Therefore, care has to be taken when blood samples collected postradiotherapeutically are used to assess the radiosensitivity of cancer patients