Online MR-guided proton and ion beam radiotherapy: investigation of image quality.

Objective.Magnetic resonance (MR) images free of artefacts are of pivotal importance for MR-guided ion radiotherapy. This study investigates MR image quality for simultaneous irradiation in an experimental setup using phantom imaging as well asin-vivoimaging. Observed artefacts are described within the study and their cause is investigated with the goal to find conclusions and solutions for potential future hybrid devices.Approach.An open MR scanner with a field strength of 0.25 T has been installed in front of an ion beamline. Simultaneous magnetic resonance imaging and irradiation using raster scanning were performed to analyze image quality in dedicated phantoms. Magnetic field measurements were performed to assist the explanation of observed artifacts. In addition,in-vivoimages were acquired by operating the magnets for beam scanning without transporting a beam.Main Results.The additional frequency component within the isocenter caused by the fringe field of the horizontal beam scanning magnet correlates with the amplitude and frequency of the scanning magnet steering and can cause ghosting artifacts in the images. These are amplified with high currents and fast operating of the scanning magnet. Applying a real-time capable pulse sequencein-vivorevealed no ghosting artifacts despite a continuously changing current pattern and a clinical treatment plan activation scheme, suggesting that the use of fast imaging is beneficial for the aim of creating high quality in-beam MR images. This result suggests, that the influence of the scanning magnets on the MR acquisition might be of negligible importance and does not need further measures like extensive magnetic shielding of the scanning magnets.Significance.Our study delimited artefacts observed in MR images acquired during simultaneous raster scanning ion beam irradiation. The application of a fast pulse sequence showed no image artefacts and holds the potential that online MR imaging in future hybrid devices might be feasible.

Mechanical behavior of idealized, stingray-skeleton-inspired tiled composites as a function of geometry and material properties.

Tilings are constructs of repeated shapes covering a surface, common in both manmade and natural structures, but in particular are a defining characteristic of shark and ray skeletons. In these fishes, cartilaginous skeletal elements are wrapped in a surface tessellation, comprised of polygonal mineralized tiles linked by flexible joints, an arrangement believed to provide both stiffness and flexibility. The aim of this research is to use two-dimensional analytical models to evaluate the mechanical performance of stingray skeleton-inspired tessellations, as a function of their material and structural parameters. To calculate the effective modulus of modeled composites, we subdivided tiles and their surrounding joint material into simple shapes, for which mechanical properties (i.e. effective modulus) could be estimated using a modification of traditional Rule of Mixtures equations, that either assume uniform strain (Voigt) or uniform stress (Reuss) across a loaded composite material. The properties of joints (thickness, Young's modulus) and tiles (shape, area and Young's modulus) were then altered, and the effects of these tessellation parameters on the effective modulus of whole tessellations were observed. We show that for all examined tile shapes (triangle, square and hexagon) composite stiffness increased as the width of the joints was decreased and/or the stiffness of the tiles was increased; this supports hypotheses that the narrow joints and high tile to joint stiffness ratio in shark and ray cartilage optimize composite tissue stiffness. Our models also indicate that, for simple, uniaxial loading, square tessellations are least sensitive and hexagon tessellations most sensitive to changes in model parameters, indicating that hexagon tessellations are the most "tunable" to specific mechanical properties. Our models provide useful estimates for the tensile and compressive properties of 2d tiled composites under uniaxial loading. These results lay groundwork for future studies into more complex (e.g. biological) loading scenarios and three dimensional structural parameters of biological tilings, while also providing insight into the mechanical roles of tessellations in general and improving the design of bioinspired materials.

Monte Carlo simulations to support start-up and treatment planning of scanned proton and carbon ion therapy at a synchrotron-based facility.

Reliable treatment planning of highly conformal scanned ion beam therapy demands accurate tools for the determination and characterization of the individual pencil-like beams building up the integral dose delivery and related mixed radiation field. At present, clinically practicable inverse treatment planning systems (TPSs) can only rely on fast-performing analytical algorithms. However, the rapidly emerging though more computationally intensive Monte Carlo (MC) methods can be employed to complement analytical TPS, e.g., via accurate calculations of the input beam-model data, together with a considerable reduction of the measuring time. Here we present the work done for the application of the FLUKA MC code to support several aspects of scanned ion beam delivery and treatment planning at the Heidelberg Ion Beam Therapy Center (HIT). Emphasis is given to the generation of the accelerator library and of experimentally validated TPS input basic data which are now in clinical use for proton and carbon ion therapy. Additionally, MC dose calculations of planned treatments in water are shown to represent a valuable tool for supporting treatment plan verification in comparison to dosimetric measurements. This paper can thus provide useful information and guidelines for the start-up and clinical operation of forthcoming ion beam therapy facilities similar to HIT.

The influence of lateral beam profile modifications in scanned proton and carbon ion therapy: a Monte Carlo study.

Scanned ion beam delivery promises superior flexibility and accuracy for highly conformal tumour therapy in comparison to the usage of passive beam shaping systems. The attainable precision demands correct overlapping of the pencil-like beams which build up the entire dose distribution in the treatment field. In particular, improper dose application due to deviations of the lateral beam profiles from the nominal planning conditions must be prevented via appropriate beam monitoring in the beamline, prior to the entrance in the patient. To assess the necessary tolerance thresholds of the beam monitoring system at the Heidelberg Ion Beam Therapy Center, Germany, this study has investigated several worst-case scenarios for a sensitive treatment plan, namely scanned proton and carbon ion delivery to a small target volume at a shallow depth. Deviations from the nominal lateral beam profiles were simulated, which may occur because of misaligned elements or changes of the beam optic in the beamline. Data have been analysed with respect to the lateral penumbra, homogeneity and coverage of the dose deposition in the target volume. The results indicate that homogeneity is not seriously compromised by extremely narrow profiles for the standard planning choices of the lateral raster scan stepping and dose grid. Differently, broad beam distributions can significantly deteriorate the conformality of the dose delivery and too large increases (above approximately 150-200% of the nominal spotsize) must be prevented.

Characteristics of cancer patients using homeopathy compared with those in conventional care: a cross-sectional study.

BACKGROUND: There are only few studies on cancer patients who are treated in complementary and alternative medicine clinics and comparing them with patients in conventional care. We will present the comparison of characteristics of two patient cohorts: one was treated in a homeopathic cancer care clinic and one was treated in a conventional oncology care (CC) outpatient clinic. PATIENTS AND METHODS: Six-hundred and forty-seven patients were included in this cross-sectional cohort study and had to fill in questionnaires [health-related quality of life (QoL) (Functional Assessment of Cancer Therapy-General Scale), depression and anxiety (Hospital Anxiety and Depression Scale), fatigue (Multidimensional Fatigue Inventory) and expectancies toward treatment]. Clinical data were extracted from medical records. This study presents the comparison of both cohorts. RESULTS: Patients in the homeopathy cohort are younger, better educated and more often employed than patients in the CC cohort. The most pronounced differences indicate longer disease histories and different diagnostic and clinical pretreatment variables. Despite the clinical differences, QoL as well as anxiety, depression and fatigue was similar in both the groups. CONCLUSIONS: Homeopathic treatment is sought by cancer patients at a different phase during the course of the disease, which has particular implications for research. However, expectancies toward the benefit of the treatment as well as QoL data are similar.

Artichoke leave extract for chronic hepatitis C - a pilot study.

BACKGROUND: Artichoke leave extracts (ALE) have hepatoprotektive properties and are used by patients with chronic liver disease. Effects in patients with chronic hepatitis C are unclear. METHODS: 17 patients with chronic hepatitis C and persistently elevated aminotransferase levels were treated for 12 weeks with 3200mg standardized ALE per day. Primary outcome parameter was the rate of alanine aminotransferase (ALT) normalisation after 12 weeks. Secondary parameters were the course of ALT, aspartate aminotransferase and gamma glutamyltransferase levels, quantitative HCV RNA, subjective symptoms frequently associated with chronic hepatitis C (fatigue, discomfort upper abdomen, joint problems) and safety. RESULTS: None of the patients had normalized ALT levels after 12 weeks of treatment. There was no significant change of aminotransferase levels or viral load compared to baseline levels. Fatigue and joint problems significantly improved after 4 weeks of treatment. However, after 12 weeks, there was no significant difference to baseline. Tolerability of ALE was rated as good to excellent. Severe side effects did not occur. CONCLUSION: ALE seem not to be effective to improve aminotransferase levels in patients with chronic hepatitis C.

[Mercury and Alzheimer's disease]. / Quecksilber und Alzheimer-Erkrankung.

Higher mercury concentrations were found in brain regions and blood of some patients with Alzheimer's disease (AD). Low levels of inorganic mercury were able to cause AD- typical nerve cell deteriorations in vitro and in animal experiments. Other metals like zinc, aluminum, copper, cadmium, manganese, iron, and chrome are not able to elicit all of these deteriorations in low levels, yet they aggravate the toxic effects of mercury (Hg). Main human sources for mercury are fish consumption (Methyl-Hg) and dental amalgam (Hg vapour). Regular fish consumption reduces the risk of development of AD. Amalgam consists of approx. 50 % of elementary mercury which is constantly being vaporized and absorbed by the organism. Mercury levels in brain tissues are 2 - 10 fold higher in individuals with dental amalgam. Persons showing a genetically determined subgroup of transportation protein for fats (apolipoprotein E4) have an increased AD risk. Apoliprotein E (APO E) is found in high concentrations in the central nervous system. The increased AD risk through APO E4 might be caused by its reduced ability to bind heavy metals. Latest therapeutic approaches to the treatment of Alzheimer disease embrace pharmaceuticals which remove or bind metals from the brain. Preliminary success has been documented with chelation of synergistic toxic metals (Fe, Al, Zn, Cu) and therefore also Hg. The available data does not answer the question, whether mercury is a relevant risk factor in AD distinctively. In sum, the findings from epidemiological and demographical studies, the frequency of amalgam application in industrialized countries, clinical studies, experimental studies and the dental state of Alzheimer patients in comparison to controls suggest a decisive role for inorganic mercury in the etiology of Alzheimer's disease. Other factors currently discussed as causes (e. g. other metals, inflammations, dietetic factors, vitamin deficiency, oxidative distress, and metabolic impairments) may act as co-factors.

Measurement of helicity-dependent photoabsorption cross sections on the neutron from 815 to 1825 MeV.

Helicity-dependent total photoabsorption cross sections on the deuteron have been measured for the first time at ELSA (Bonn) in the photon energy range from 815 to 1825 MeV. Circularly polarized tagged photons impinging on a longitudinally polarized LiD target have been used together with a highly efficient 4pi detector system. The data around 1 GeV are not compatible with predictions from existing multipole analyses. From the measured energy range an experimental contribution to the GDH integral on the neutron of [33.9 +/- 5.5(stat) +/- 4.5(syst)] microb is extracted.

[Amalgam risk assessment with coverage of references up to 2005]. / Amalgam: Eine Risikobewertung unter Berücksichtigung der neuen Literatur bis 2005.

Amalgam, which has been in use in dentistry for 150 years, consists of 50 % elemental mercury and a mixture of silver, tin, copper and zinc. Minute amounts of mercury vapour are released continuously from amalgam. Amalgam contributes substantially to human mercury load. Mercury accumulates in some organs, particularly in the brain, where it can bind to protein more tightly than other heavy metals (e. g. lead, cadmium). Therefore, the elimination half time is assumed to be up to 1 - 18 years in the brain and bones. Mercury is assumed to be one of the most toxic non-radioactive elements. There are pointers to show that mercury vapour is more neurotoxic than methyl-mercury in fish. Review of recent literature suggests that mercury from dental amalgam may lead to nephrotoxicity, neurobehavioural changes, autoimmunity, oxidative stress, autism, skin and mucosa alterations or non-specific symptoms and complaints. The development of Alzheimer's disease or multiple sclerosis has also been linked to low-dose mercury exposure. There may be individual genetical or acquired susceptibilities for negative effects from dental amalgam. Mercury levels in the blood, urine or other biomarkers do not reflect the mercury load in critical organs. Some studies regarding dental amalgam reveal substantial methodical flaws. Removal of dental amalgam leads to permanent improvement of various chronic complaints in a relevant number of patients in various trials. Summing up, available data suggests that dental amalgam is an unsuitable material for medical, occupational and ecological reasons.

Amalgam studies: disregarding basic principles of mercury toxicity.

Dental amalgam, which has been used for over 150 years in dental practice, consists of about 50% metallic mercury. Studies on animal and humans show that mercury is continuously released from dental amalgam and absorbed by several body tissues. It is widely accepted that the main source of mercury vapor is dental amalgam and it contributes substantially to mercury load in human body tissues. There is still a controversy about the consequences of this additional mercury exposure from amalgam to human health. Many studies were performed to evaluate possible adverse effects. In this comment, these studies were analyzed with regard to their methodical quality by considering the newest findings on mercury toxicity and metabolism. In sum, a number of studies are methodically flawed drawing inaccurate conclusions as to the safety of dental amalgam.

Experimental check of the Gerasimov-Drell-Hearn sum rule for 1H.

For the first time we checked the fundamental Gerasimov-Drell-Hearn (GDH) sum rule for the proton experimentally in the photon energy range from 0.2-2.9 GeV with the tagged photon facilities at MAMI (Mainz) and ELSA (Bonn). New data of the doubly polarized total cross section difference are presented in the energy range from 1.6 to 2.9 GeV. The contribution to the GDH integral from 0.2-2.9 GeV yields [254+/-5(stat)+/-12(syst)] microb with negative contributions in the Regge regime at photon energies above 2.1 GeV. This trend supports the validity of the GDH sum rule.

First Measurement of the Gerasimov-Drell-Hearn Sum Rule for 1H from 0.7 to 1.8 GeV at ELSA.

To verify the fundamental Gerasimov-Drell-Hearn (GDH) sum rule for the first time experimentally, we measured the helicity dependent total photoabsorption cross section with circularly polarized real photons and longitudinally polarized nucleons in the photon energy range 0.68-1.82 GeV with the tagged photon facility at ELSA. The experiment was carried out with a 4pi detection system, a circularly polarized tagged photon beam, and a frozen spin polarized proton target. The contribution to the GDH sum rule in this photon energy range is [49.9+/-2.4(stat)+/-2.2(syst)] microb.

SAP and partners: IS-H and IS-H* MED.

OBJECTIVES: The Styrian Hospital Organization with 21 hospitals including the Graz University Hospital, and the Heidelberg University Hospital implemented a new HIS based on SAP/R3, ISH, ISH* MED with the objective to have an integrated system to support patient administration and management, patient care, clinical documentation, research etc. METHODS: Heidelberg University Hospital chose a step by step method for the introduction of the system, beginning with patient administration (ISH) and proceeding with clinical functions (ISH* MED). In Styria, the full functionality was implemented--as part of the selection process--in one peripheral hospital and in the Ear, Nose and Throat (ENT) Department of the Graz University Hospital, including special documents to support the processes in the highly specialized ENTunits. RESULTS AND CONCLUSIONS: The standard modules are performant, stable and basically well accepted. Particularly in Graz, it has been shown that the requirements of highly specialized departments for work flow management, documentation and integration of subsystems and data from different sources can be fulfilled by special documents and programs--although at the expense of additional workload particularly in the initial phases of such a project.

Helicity amplitudes A1/2 and A3/2 for the D13(1520) resonance obtained from the gamma-->p-->-->ppi(0) Reaction.

The helicity dependence of the gamma-->p-->-->ppi(0) reaction has been measured for the first time in the photon-energy range from 550 to 790 MeV. The experiment, performed at the Mainz microtron MAMI, used a 4pi-detector system, a circularly polarized, tagged photon beam, and a longitudinally polarized frozen-spin target. These data are predominantly sensitive to the D13(1520) resonance and are used to determine its helicity amplitudes.

Response times in attitudinal items as indicators of the continuous accessibility of knowledge related to attitudes.

In the paradigm of social cognition, the measurement of response latencies is important not only for priming procedures directed at the cognitive representation, but also for the assessment of strength-related properties of attitudes. The present paper explored the possibility of using response times as indicators of the continuous accessibility of attitude-relevant knowledge. For two different sets of attitudinal items concerning social welfare (idiographic and nomothetic selection) response times were obtained from a sample of 20 university students. In addition to different reliability coefficients for aggregated response times, information about individual subjects' consistencies and stabilities was obtained. Further, evidence for the validity of response times as indicators of the continuous accessibility of attitude-related knowledge is reported. The aggregated response times had significant correlations with self-report data and interview-related variables (such as number of propositions mentioned) which were obtained by a content analysis of semistructured interviews.

Helicity dependence of gammap --> Npi below 450 MeV and contribution to the Gerasimov-Drell-Hearn sum rule.

The helicity dependence of the single pion photoproduction on the proton has been measured in the energy range from 200 to 450 MeV for the first time. The experiment, performed at the Mainz microtron MAMI, used a 4pi-detector system, a circularly polarized, tagged photon beam, and a frozen-spin target. The data obtained provide new information for multipole analyses of pion photoproduction and determine the main contributions to the Gerasimov-Drell-Hearn sum rule and the forward spin polarizability gamma(0).

Comparison of sensitivity towards photodynamic therapy of cutaneous resident and infiltrating cell types in vitro.

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) combines photosensitizers absorbing light in the visible spectral region and irradiation with light of corresponding wavelengths. We analysed the sensitivity of cell lines established from resident cutaneous cells and from transformed lymphocytes towards PDT. STUDY DESIGN/MATERIALS AND METHODS: PDT was performed employing either 630 or 662 nm light or polychromatic red light (600-700 nm) and photosensitizers Photosan-3, delta-aminolevulinic acid, or methylene blue. Proliferation measured by 3H-TdR uptake was determined in human immortalized keratinocytes (HaCaT) and mouse fibroblasts (NIH/3T3) in comparison to human transformed T-(HuT78) and B-lymphocytes (RA1). Additionally, uptake of the photosensitizers was estimated employing video-intensified fluorescence-microscopy (VIFM). RESULTS: Depending on the photosensitizer tested HaCaT and NIH/3T3 exhibited an ED50 up to 10-fold as high as the lymphocytic lines. Polychromatic red light was at least as effective at inducing photodynamic reactions as 630 or 662 nm light. VIFM revealed a positive correlation between sensitivity of a given cell type towards PDT and uptake of the photosensitizers. The differential uptake observed in vitro was confirmed in vivo: A photosensitizer applied topically on a lesion of a patient with mycosis fungoides was found to accumulate preferentially in the lymphocytic infiltrate. CONCLUSION: Selective topical polychromatic PDT seems to be a feasible goal for the treatment of cutaneous lymphomas.

[Local administration of vaginal therapeutic drugs and their possible side effects]. / Die lokale Applikation von vaginalen Therapeutika und ihre möglichen Nebenwirkungen.

We have proved with screening-electron-microscopic examinations that different chemical substances bend to formation of cristals on the vaginal skin. Different size of the cristals depends from different quantities of the drugs. Cytotoxic appearances are possible.

[Calcium oxalate activity products and discriminant analysis of urinary parameters as basis for a calcium oxalate screening program (author's transl)]. / Kalzium-Oxalat-Aktivitätsprodukte und diskriminanzanalytische Verrechnungen von Harnparametern als Grundlage eines Kalzium-Oxalat-Screening-Programmes.

The values of 7 urinary parameters in divided urine collections were measured in 20 patients with calcium oxalate stones and ten normal persons. On this basis the thermodynamic stone formation risk was calculated for the different urine collections. Stone formation risk in the 0-6 a.m. urine fractions appeared to be the most important. The risk of stone formation is significantly increased in the time from midnight to 6 a.m. To detect the risk situation the determination of oxalic acid, calcium, potassium and inorganic sulfate in night urine is adequate.