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Background: While recent data show that crizotinib is highly effective in patients with ROS1 rearrangement, few data is available about the prognostic impact, the predictive value for different treatments, and the genetic heterogeneity of ROS1- positive patients.
Patients and methods: 1137 patients with adenocarcinoma of the lung were analyzed regarding their ROS1 status. In positive cases, next-generation sequencing (NGS) was performed. Clinical characteristics, treatments and outcome of these patients were assessed. Overall survival (OS) was compared with genetically defined subgroups of ROS1-negative patients.
Results: 19 patients of 1035 evaluable (1.8%) had ROS1-rearrangement. The median OS has not been reached. Stage IV patients with ROS1-rearrangement had the best OS of all subgroups (36.7 months, p < 0.001). 9 of 14 (64.2%) patients had at least one response to chemotherapy. Estimated mean OS for patients receiving chemotherapy and crizotinib was 5.3 years. Ten patients with ROS1-rearrangement (52.6%) harbored additional aberrations.
Conclusion: ROS1-rearangement is not only a predictive marker for response to crizotinib, but also seems to be the one of the best prognostic molecular markers in NSCLC reported so far. In stage IV patients, response to chemotherapy was remarkable high and overall survival was significantly better compared to other subgroups including EGFR-mutated and ALK-fusion-positive NSCLC.
The crossbar-H-mode (CH) structure is the first superconducting multicell drift tube cavity for the low and medium energy range operated in the H21 mode. Because of the large energy gain per cavity, which leads to high real estate gradients, it is an excellent candidate for the efficient acceleration in high power proton and ion accelerators with fixed velocity profile. A prototype cavity has been developed and tested successfully with a gradient of 7MV/m. A few new superconducting CH cavities with improved geometries for different high power applications are under development at present. One cavity (f=325 MHz, β=0.16, seven cells) is currently under construction and studied with respect to a possible upgrade option for the GSI UNILAC. Another cavity (f=217 MHz, β=0.059, 15 cells) is designed for a cw operated energy variable heavy ion linac application. Furthermore, the EUROTRANS project (European research program for the transmutation of high level nuclear waste in an accelerator driven system, 600 MeV protons, 352 MHz) is one of many possible applications for this kind of superconducting rf cavity. In this context a layout of the 17 MeV EUROTRANS injector containing four superconducting CH cavities was proposed by the Institute for Applied Physics (IAP) Frankfurt. The status of the cavity development related to the EUROTRANS injector is presented.
A modern linear accelerator of ions is a long chain of different accelerating-focusing structures. The design of new linacs, as well as an upgrade and optimization of operating facilities, requires precise and reliable beam matching with the subsequent sections. Proper matching of the beam to the channel allows to improve the performance of the whole linac and to reduce the specific costs. Additionally it helps to avoide particle loss in high energy high intensity linacs. Generally a matching algorithm combines precisely measured or calculated accelerating-focusing external fields and experimentally obtained details of the beam parameters with an advanced code for beam dynamics simulations including space charge effects. Experimental results are introduced into a code as input data. The described algorithm has already been successfully implemented for several GSI projects: an upgrade of the GSI heavy ion linac UNILAC, an ion linac for the cancer therapy, the proton linac for the FAIR facility, a facility for laser acceleration of ions and others. Measured data and results of beam dynamics simulations leading to an achieved improvement of the linac performance are presented.
The crossbar H-mode (CH) cavity is an accelerating structure operated in the H21(0) mode. The robustness of the crossbar geometry allows one to realize room temperature as well as superconducting linac cavities. The shunt impedance characteristics of this structure are attractive to develop proton and heavy ion linacs in the low and medium beta range. A first room temperature eight-cell prototype has proven the feasibility of the crossbar design in terms of mechanical construction, copper plating, and cooling. An innovative rf coupling concept has been developed where two CH cavities are connected by a two gap E010-mode resonator which, at the same time, provides transverse focusing by a quadrupole triplet. The concept has been applied in the design of the new FAIR proton linac and a scaled model of the second cavity of this injector has been built and tested too. The full scale prototype is now under construction at the University of Frankfurt. In this paper, the room temperature CH cavity development as well as the general layout of the FAIR proton injector (70 MeV, 325 MHz, 70 mA) is presented and discussed.
In diesem Aufsatz wird das mentale Lexikon als System beschrieben, in dem Lexeme aufgenommen, gespeichert und nach bestimmten Regeln geordnet und eingesetzt werden. Hierbei spielen Bedeutungsbeziehungen eine grundlegende Rolle. Die Mikrostruktur dieses Netzwerks bildet die Polysemie, die anhand von Bedeutungssternen (mit Kernbedeutung und Nebenbedeutungen einzelner Lexeme) dargestellt werden kann. Anhand von Musterübungen wird gezeigt, wie dieses Thema im muttersprachlichen Unterricht didaktisch umgesetzt werden kann.
Superconducting, energy variable heavy ion linac with constant
β, multicell cavities of CH-type
(2009)
An energy variable ion linac consisting of multigap, constant-β cavities was developed. The effect of phase sliding, unavoidable in any constant-β section, is leading to a coherent rf phase motion, which fits well to the H-type structures with their long π-mode sections and separated lenses. The exact periodicity of the cell lengths within each cavity results in technical advantages, such as higher calculation accuracy when only one single period can be simulated, simpler manufacturing, and tuning. This is most important in the case of superconducting cavities. By using this concept, an improved design for a 217 MHz cw superconducting heavy ion linac with energy variation has been worked out. The small output energy spread of ± 3 AkeV is provided over the whole range of energy variation from 3.5 to 7.3 AMeV. These capabilities would allow for a competitive research in the field of radiochemistry and for a production of super heavy elements (SHE), especially. A first 19-cell cavity of that type was designed, built, and rf tested successfully at the Institute for Applied Physics (IAP) Frankfurt. A 325.224 MHz, seven-cell cavity with constant β = 0.16 is under development and will be operated in a frequency controlled mode. It will be equipped with a power coupler and beam tests with Unilac beams at GSI are foreseen.
BACKGROUND: hysical activity exerts a variety of long-term health benefits in older adults. In particular, it is assumed to be a protective factor against cognitive decline and dementia.
METHODS/DESIGN: Randomised controlled assessor blinded 2-armed trial (n = 60) to explore the exercise- induced neuroprotective and metabolic effects on the brain in cognitively healthy older adults. Participants (age ≥ 65), recruited within the setting of assisted living facilities and newspaper advertisements are allocated to a 12-week individualised aerobic exercise programme intervention or a 12-week waiting control group. Total follow-up is 24 weeks. The main outcome is the change in cerebral metabolism as assessed with Magnetic Resonance Spectroscopic Imaging reflecting changes of cerebral N-acetyl-aspartate and of markers of neuronal energy reserve. Imaging also measures changes in cortical grey matter volume. Secondary outcomes include a broad range of psychometric (cognition) and movement-related parameters such as nutrition, history of physical activity, history of pain and functional diagnostics. Participants are allocated to either the intervention or control group using a computer-generated randomisation sequence. The exercise physiologist in charge of training opens sealed and opaque envelopes and informs participants about group allocation. For organisational reasons, he schedules the participants for upcoming assessments and exercise in groups of five. All assessors and study personal other than exercise physiologists are blinded.
DISCUSSION: Magnetic Resonance Spectroscopic Imaging gives a deeper insight into mechanisms of exercise-induced changes in brain metabolism. As follow-up lasts for 6 months, this study is able to explore the mid-term cerebral metabolic effects of physical activity assuming that an individually tailored aerobic ergometer training has the potential to counteract brain ageing.
NCT02343029 (clinicaltrials.gov; 12 January 2015).
There is mounting evidence that aerobic exercise has a positive effect on cognitive functions in older adults. To date, little is known about the neurometabolic and molecular mechanisms underlying this positive effect. The present study used magnetic resonance spectroscopy and quantitative MRI to systematically explore the effects of physical activity on human brain metabolism and grey matter (GM) volume in healthy aging. This is a randomised controlled assessor-blinded two-armed trial (n=53) to explore exercise-induced neuroprotective and metabolic effects on the brain in cognitively healthy older adults. Participants (age >65) were allocated to a 12-week individualised aerobic exercise programme intervention (n=29) or a 12-week waiting control group (n=24). The main outcomes were the change in cerebral metabolism and its association to brain-derived neurotrophic factor (BDNF) levels as well as changes in GM volume. We found that cerebral choline concentrations remained stable after 12 weeks of aerobic exercise in the intervention group, whereas they increased in the waiting control group. No effect of training was seen on cerebral N-acetyl-aspartate concentrations, nor on markers of neuronal energy reserve or BDNF levels. Further, we observed no change in cortical GM volume in response to aerobic exercise. The finding of stable choline concentrations in the intervention group over the 3 month period might indicate a neuroprotective effect of aerobic exercise. Choline might constitute a valid marker for an effect of aerobic exercise on cerebral metabolism in healthy aging.
The HITRAP linear decelerator currently being set up at GSI will provide slow, few keV/u highly charged ions for atomic physics experiments. The expected beam intensity is up to 105 ions per shot. To optimize phase and amplitude of the RF systems intensity, bunch length and kinetic energy of the particles need to be monitored. The bunch length that we need to fit is about 2 ns, which is typically measured by capacitive pickups. However, they do not work for the low beam intensities that we face. We investigated the bunch length with a fast CVD diamond detector working in single particle counting mode. Averaging over 8 shots yields a clear, regular picture of the bunched beam. Energy measurements by capacitive pickups are limited by the presence of intense primary and partially decelerated beam and hence make tuning of the IH-structure impossible. The energy of the decelerated fraction of the beam behind the first deceleration cavity was determined to about 10 % accuracy with a permanent dipole magnet combined with a MCP. Better detector calibration should help reaching the required 1%. Design of the detectors as well as the results of the measurements will be presented.
At the Institute for Applied Physics (IAP), University of Frankfurt, a s.c. 325 MHz CH-Cavity is under development for future beam tests at GSI UNILAC, Darmstadt. The cavity with 7 accelerating cells has a geometrical beta of 0.15 corresponding to 11.4 AMeV. The design gradient is 5 MV/m. The geometry of this resonator was optimized with respect to a compact design, low peak fields, surface processing, power coupling and tuning. Furthermore a new tuning system based on bellow tuners inside the resonator will control the frequency during operation. After rf tests in Frankfurt the cavity will be tested with a 10 mA, 11.4 AMeV beam delivered by the GSI UNILAC. In this paper rf simulations, multipacting analysis as well as thermal calculations will be presented.