Hippocampus-avoidance whole-brain radiation therapy with a simultaneous integrated boost for multiple brain metastases.

BACKGROUND: The current study was aimed at investigating the feasibility of hippocampus-avoidance whole-brain radiation therapy with a simultaneous integrated boost (HA-WBRT+SIB) for metastases and at assessing tumor control in comparison with conventional whole-brain radiation therapy (WBRT) in patients with multiple brain metastases. METHODS: Between August 2012 and December 2016, 66 patients were treated within a monocentric feasibility trial with HA-WBRT+SIB: hippocampus-avoidance WBRT (30 Gy in 12 fractions, dose to 98% of the hippocampal volume ≤ 9 Gy) and a simultaneous integrated boost (51 or 42 Gy in 12 fractions) for metastases/resection cavities. Intracranial tumor control, hippocampal failure, and survival were subsequently compared with a retrospective cohort treated with WBRT via propensity score matching analysis. RESULTS: After 1:1 propensity score matching, there were 62 HA-WBRT+SIB patients and 62 WBRT patients. Local tumor control (LTC) of existing metastases was significantly higher after HA-WBRT+SIB (98% vs 82% at 1 year; P = .007), whereas distant intracranial tumor control was significantly higher after WBRT (82% vs 69% at 1 year; P = .016); this corresponded to higher biologically effective doses. Intracranial progression-free survival (PFS; 13.5 vs 6.4 months; P = .03) and overall survival (9.9 vs 6.2 months; P = .001) were significantly better in the HA-WBRT+SIB cohort. Four patients (6.5%) developed hippocampal metastases after hippocampus avoidance. The neurologic death rate after HA-WBRT+SIB was 27.4%. CONCLUSIONS: HA-WBRT+SIB can be an efficient therapeutic option for patients with multiple brain metastases and is associated with improved LTC of existing metastases, higher intracranial PFS, a reduction of the neurologic death rate, and an acceptable risk of radiation necrosis. The therapy has the potential to prevent neurocognitive adverse effects, which will be further evaluated in the multicenter, phase 2 HIPPORAD trial.

Research potential and limitations of trace analyses of cremated remains.

Human cremation is a common funeral practice all over the world and will presumably become an even more popular choice for interment in the future. Mainly for purposes of identification, there is presently a growing need to perform trace analyses such as DNA or stable isotope analyses on human remains after cremation in order to clarify pending questions in civil or criminal court cases. The aim of this study was to experimentally test the potential and limitations of DNA and stable isotope analyses when conducted on cremated remains. For this purpose, tibiae from modern cattle were experimentally cremated by incinerating the bones in increments of 100°C until a maximum of 1000°C was reached. In addition, cremated human remains were collected from a modern crematory. The samples were investigated to determine level of DNA preservation and stable isotope values (C and N in collagen, C and O in the structural carbonate, and Sr in apatite). Furthermore, we assessed the integrity of microstructural organization, appearance under UV-light, collagen content, as well as the mineral and crystalline organization. This was conducted in order to provide a general background with which to explain observed changes in the trace analyses data sets. The goal is to develop an efficacious screening method for determining at which degree of burning bone still retains its original biological signals. We found that stable isotope analysis of the tested light elements in bone is only possible up to a heat exposure of 300°C while the isotopic signal from strontium remains unaltered even in bones exposed to very high temperatures. DNA-analyses seem theoretically possible up to a heat exposure of 600°C but can not be advised in every case because of the increased risk of contamination. While the macroscopic colour and UV-fluorescence of cremated bone give hints to temperature exposure of the bone's outer surface, its histological appearance can be used as a reliable indicator for the assessment of the overall degree of burning.

Structure of strontium barium niobate SrxBa1-xNb2O6 (SBN) in the composition range 0.32

The structure of strontium barium niobate crystals SrxBa1-xNb2O6 is comprehensively studied in the whole range of the tetragonal tungsten bronze phase (x=0.32-0.82) using both powder and single-crystal X-ray diffraction measurements. Unit-cell parameters, density, site-occupancy factors and interionic distances show an explicit composition dependence which can be consistently explained using simple model calculations. The temperature dependence of the unit-cell parameters exhibits a remarkable anisotropy in a broad temperature region below the phase transition temperature. This proves that the electrostrictive contribution to the thermal expansion plays an important role in strontium barium niobate.

Different protection mechanisms after pretreatment with glycine or alpha-lipoic acid in a rat model of warm hepatic ischemia.

BACKGROUND/AIM: Alpha-lipoic (LA) acid pretreatment has previously been described to reduce ischemia/reperfusion injury (IRI) after warm liver ischemia, whereas glycine pretreatment has been shown to be protective mostly in models of cold hepatic ischemia. The aim of this study was to determine whether glycine decreases IRI after warm hepatic ischemia. Furthermore we investigated whether doses of LA other than those used previously are also protective against IRI after warm hepatic ischemia. METHODS: Selective liver ischemia was maintained over a period of 90 min. In long-term as well as short-term experiments we studied IRI in several groups comparing animal survival as the pivotal endpoint. RESULTS: Animal survival was improved by glycine and 5,000 micromol LA, whereas all animals died within 3 days after pretreatment with 50 micromol LA. In the glycine group we observed a tendency towards decreased apoptosis-related cell death measured by the activity of caspase-3 in liver tissue and the percentage of TUNEL-positive hepatocytes in comparison to the untreated group. Serum alpha-glutathione S-transferase, lipid peroxidation, and caspase-3 activity as well as the percentage of TUNEL-positive hepatocytes and the percentage of liver necrosis were only significantly decreased by 5,000 micromol LA pretreatment. Liver tissue levels of tumor necrosis factor (TNF)alpha were reduced only in the glycine group whereas TNFalpha was increased in the untreated as well as the LA group. Levels of TNFalpha mRNA were upregulated in both the glycine- and LA-pretreated groups. CONCLUSION: Our data show that increased animal survival by glycine was accompanied by a reduced TNFalpha content in liver tissue. Protection by glycine is likely to result from a reduction in adverse TNFalpha effects. Administration of high-dose LA on the other hand led to a significant reduction in necrosis- and apoptosis-related cell death in IRI of the liver without a reduction in liver TNFalpha.