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Biomedical subjects

J Siebers

Publications and source records attributed to J Siebers.

14 recordsLinked to original sources

Chromosomal imbalances and NF2 mutational analysis in a series of 10 spinal nerve sheath myxomas.

AIMS: To report the demographic, clinical and molecular profile of a series of intraspinal nerve sheath myxomas. Nerve sheath myxomas are diagnostically challenging, mainly cutaneous spindle cell neoplasms exhibiting Schwann cell differentiation. They are frequently mistaken for neurothekeomas and their genetic features are essentially unknown. METHODS AND RESULTS: Ten spinal nerve sheath myxomas with a preferential location in the lumbar spine (70%) were investigated. Presenting symptoms consisted of sciatic pain (100%), muscle weakness and paraesthesia (60% each). Intraoperatively, all tumours were attached to a spinal nerve. Chromosomal imbalances by comparative genomic hybridization were found in 8/10 cases, consisting of -22q (80%) and -19 (30%). Polymerase chain reaction analysis of the NF2 gene (exons 1-16) revealed two tumours with mutations in exon 8 and 14, respectively. CONCLUSIONS: Although these 10 nerve sheath myxomas exhibited Schwann cell differentiation and frequently showed loss of chromosome 22q typically encountered in peripheral nerve tumours, only two cases demonstrated mutations of the NF2 gene. This may indicate involvement of other tumour suppressor genes on 22q in nerve sheath myxomas and shows that they are more closely related at the molecular level to sporadic schwannomas, underscoring the presumption that they are true nerve sheath tumours.

Adult↗

Isomeric transitions in size-selected methanol hexamers probed by OH-stretch spectroscopy.

We have measured the isomeric transition between the energetically lowest lying isomers of S6 and C2-symmetry of (CH3OH)6. The clusters are size-selected by deflection in collisions with He, and the isomers are identified by their infrared spectra of the OH-stretching vibration. The measurements are carried out at three source temperatures 253, 300 and 373 K which correspond to the cluster temperatures 93, 106 and 135 K. The latter ones are estimated by a relaxation model that accounts for the cluster formation and the energy released by the condensation. The transition takes place at a cluster temperature of about 102 K which is in agreement with the Molecular Dynamics simulation of such a transition at about 117 K using a realistic model potential.

Computer Simulation↗

Aerial short-range dispersion of volatilized pesticides from an area source.

Owing to legal provisions, pesticides have to be applied in such a way that there is no unacceptable influence on human health and the environment at nearby non-target areas. In order to quantify their concentration over and downwind of agricultural target plots of 0.5-1 ha, covered by winter wheat and winter barely, the pesticides lindane, parathion and pirimicarb were applied. Over these plots the post-application volatilization rates of the pesticides were estimated indirectly from vertical concentration, wind and temperature profile measurements using the aerodynamic gradient technique. Philip's advection model was applied to take non-favourable fetch conditions into account. In addition, at a height of 1.6 m downwind of the area source, measurements of the horizontal concentration profile were made up to a distance of about 250 m at roughly 50-m intervals. The monitoring started immediately after spraying in the morning and continued for about 8-10 h, thus providing a worst-case situation because volatilization, and therefore pesticide concentration in the atmospheric surface layer, is then strongest. The concentration of the airborne pesticides over the downwind non-target area was also calculated by Philip's advection model. By using the Nash-Sutcliffe relative-difference measure between observed and calculated concentrations, a goodness-of-fit of 0.97 was obtained over the downwind non-target area, indicating that the Philip model is well suited for dispersion estimates in the near-field range.

Agriculture↗

The impact of fluctuations in intensity patterns on the number of monitor units and the quality and accuracy of intensity modulated radiotherapy.

The purpose of this work is to examine the potential impact of the frequency and amplitude of fluctuations ("complexity") in intensity distributions on intensity-modulated radiotherapy (IMRT) dose distributions. The intensity-modulated beams are efficiently delivered using a multileaf collimator (MLC). Radiation may be delivered through a continuous (dynamic mode) or discrete (step-and-shoot) sequence of windows formed by the leaves. Algorithms and software that convert optimized intensity distributions into leaf trajectories apply approximate empirical corrections to account for the various effects associated with MLC characteristics, such as the rounded leaf tips, tongue-and-groove leaf design, leaf transmission, leaf scatter, and collimator scatter upstream from the MLC. Typically, the difference between inter- and intraleaf transmissions is ignored. In this paper, using a schematic example of IMRT for head and neck carcinomas, we demonstrate that complex anatomy and severe optimization constraints produce complex intensity patterns. Using idealized intensity patterns we also demonstrate that, for complex intensity patterns, the average window width tends to be smaller and, for the same dose received by the tumor, the number of MUs is larger. We found that as the complexity increases, so does the contribution of radiation transmitted through and scattered from the leaves ("indirect radiation") to the total delivered dose. As a consequence, the lowest deliverable intensity in complex intensity patterns may be significantly greater than that required to provide adequate protection for some normal tissues. Furthermore, since corrections for leaf transmission and scatter effects are approximate and the difference between inter- and intraleaf transmission is ignored, the accuracy of the delivered dose may be affected. Using the results of a simple experiment and a typical intensity-modulated beam for a head and neck case as examples, we show the effect of window width and complexity on the accuracy and deliverability of intensity patterns. Some possible strategies for improving the accuracy and for relaxing the lower limit on deliverable intensity are discussed.

Biophysical Phenomena↗

The impact of electron transport on the accuracy of computed dose.

The aim of this work was to investigate the accuracy of dose predicted by a Batho power law correction, and two models which account for electron range: A superposition/convolution algorithm and a Monte Carlo algorithm. The results of these models were compared in phantoms with cavities and low-density inhomogeneities. An idealized geometry was considered with inhomogeneities represented by regions of air and lung equivalent material. Measurements were performed with a parallel plate ionization chamber, thin TLDs (thermoluminescent dosimeters) and film. Dose calculations were done with a generalized Batho model, the Pinnacle collapsed cone convolution model (CCC), and the Peregrine Monte Carlo dose calculation algorithm. Absolute central axis and off axis dose data at various depths relative to interfaces of inhomogeneities were compared. Our results confirm that for a Batho correction, dose errors in the calculated depth dose arise from the neglect of electron transport. This effect increases as the field size decreases, as the density of the inhomogeneity decreases, and with the energy of incident photons. The CCC calculations were closer to measurements than the Batho model, but significant discrepancies remain. Monte Carlo results agree with measurements within the measurement and computational uncertainties.

Air↗

Validation of Monte Carlo generated phase-space descriptions of medical linear accelerators.

The accuracy of Monte Carlo codes in dose calculation systems relies on the correctness of the input data. Monte Carlo calculations are performed to generate phase-space descriptions of the Varian 2100C accelerator at 6 and 18 MeV. Before these data can be reliably used as the input for dose calculations in patients, they must be properly validated. This validation consists of three different stages: validation of the coding of the geometry, validation of the user code for the Monte Carlo code, and validation of calculated results. Geometric validation is performed by isolating and testing treatment head components independently. The user code is checked by testing for energy conservation and the variance reduction schemes incorporated into the user code are checked by comparison of results calculated with and without their employment. Validation of the phase-space description is performed by calculation of depth dose curves and lateral profiles for dose deposition in phantom, with difference plots used to illustrate any discrepancies. Calculated and experimental in-phantom output is also determined. After complete validation, the calculated data can then be reliably used as the input for dose calculations.

Biophysical Phenomena↗

Proton beam output measurement with an extrapolation chamber.

A variable air-volume, parallel-plate extrapolation chamber forming an integral part of a polystyrene phantom was used in measurement of dose rate in a 250 MeV clinical proton beam. The sensitive air-volume of the extrapolation chamber is controlled through the movement of the chamber piston by means of a micrometer mounted on the phantom body. The relative displacement of the piston is monitored by a calibrated mechanical distance travel indicator. The proton beam dose rate determined with the uncalibrated extrapolation chamber was 5% lower than the dose rate determined with a calibrated Farmer-type thimble chamber at the same depth in the polystyrene phantom. Despite the current 5% discrepancy, uncalibrated extrapolation chambers may offer a simple and practical alternative to current techniques used in output measurements of proton beam machines.

Calibration↗

Proton dosimetry intercomparison.

BACKGROUND AND PURPOSE: Methods for determining absorbed dose in clinical proton beams are based on dosimetry protocols provided by the AAPM and the ECHED. Both groups recommend the use of air-filled ionization chambers calibrated in terms of exposure or air kerma in a 60Co beam when a calorimeter or Faraday cup dosimeter is not available. The set of input data used in the AAPM and the ECHED protocols, especially proton stopping powers and w-value is different. In order to verify inter-institutional uniformity of proton beam calibration, the AAPM and the ECHED recommend periodic dosimetry intercomparisons. In this paper we report the results of an international proton dosimetry intercomparison which was held at Loma Linda University Medical Center. The goal of the intercomparison was two-fold: first, to estimate the consistency of absorbed dose delivered to patients among the participating facilities, and second, to evaluate the differences in absorbed dose determination due to differences in 60Co-based ionization chamber calibration protocols. MATERIALS AND METHODS: Thirteen institutions participated in an international proton dosimetry intercomparison. The measurements were performed in a 15-cm square field at a depth of 10 cm in both an unmodulated beam (nominal accelerator energy of 250 MeV) and a 6-cm modulated beam (nominal accelerator energy of 155 MeV), and also in a circular field of diameter 2.6 cm at a depth of 1.14 cm in a beam with 2.4 cm modulation (nominal accelerator energy of 100 MeV). RESULTS: The results of the intercomparison have shown that using ionization chambers with 60Co calibration factors traceable to standard laboratories, and institution-specific conversion factors and dose protocols, the absorbed dose specified to the patient would fall within 3% of the mean value. A single measurement using an ionization chamber with a proton chamber factor determined with a Faraday cup calibration differed from the mean by 8%. CONCLUSION: The adoption of a single ionization chamber dosimetry protocol and uniform conversion factors will establish agreement on proton absorbed dose to approximately 1.5%, consistent with that which has been observed in high-energy photon and electron dosimetry.

Calibration↗

Application of solid state detectors for dosimetry of therapeutic proton beams.

A PTW Riga diamond detector and LiF TLDs have been evaluated for use in proton beam dosimetry by comparing results of proton beam calibration with those obtained using thimble ionization chambers. The thimble ionization chambers were calibrated in terms of exposure while the TLDs and diamond detector were calibrated in terms of absorbed dose in a 60Co beam. Absorbed doses to muscle in proton beams for ionization chambers were derived using the TG 20 charged particle protocol. Absorbed doses to muscle for solid state detectors were derived using absorbed dose proton beam quality correction factors. Differences between the derived doses for ionization chambers and solid state detectors were found to be within the uncertainties of measurements: 4.5% for ionization chambers and 5% for solid state detectors.

Cobalt Radioisotopes↗

[Metabolic products of microorganisms. 175. Tetracenomycin C (author's transl)].

Streptomyces glaucescens, strain Tü 49 = ETH 22794, produces hydroxystreptomycin as well as the tetracenomycins, a mixture of several lipophilic antibiotics. The main component and the most active one is tetracenomycin C. Tetracenomycin C has a molecular formula C23H20O11 and is chemically related to tetracyclines and anthracyclinones. The pale yellow antibiotic is active against some gram-positive bacteria, especially against streptomycetes. Gram-negative bacteria and fungi are not inhibited. In considering the differences of biological activity and the functional groups of the molecule, tetracenomycin C is not a member of the tetracycline or anthracyclinone group of antibiotics.

Anti-Bacterial Agents↗

A prototype beam delivery system for the proton medical accelerator at Loma Linda.

A variable energy proton accelerator was commissioned at Fermi National Accelerator Laboratory for use in cancer treatment at the Loma Linda University Medical Center. The advantages of precise dose localization by proton therapy, while sparing nearby healthy tissue, are well documented [R. R. Wilson, Radiology 47, 487 (1946); M. Wagner, Med. Phys. 9, 749 (1982); M. Goitein and F. Chen, Med. Phys. 10, 831 (1983)]. One of the components of the proton therapy facility is a beam delivery system capable of delivering precise dose distributions to the target volume in the patient. To this end, a prototype beam delivery system was tested during the accelerator's commissioning period. The beam delivery system consisted of a beam spreading device to produce a large, uniform field, a range modulator to generate a spread out Bragg peak (SOBP), and various beam detectors to measure intensity, beam centering, and dose distributions. The beam delivery system provided a uniform proton dose distribution in a cylindrical volume of 20-cm-diam area and 9-cm depth. The dose variations throughout the target volume were found to be less than +/- 5%. Modifications in the range modulator should reduce this considerably. The central axis dose rate in the region of the SOBP was found to be 0.4 cGy/spill with an incident beam intensity of 6.7 x 10(9) protons/spill. With an accelerator repetition rate of 30 spills/min and expected intensity of 2.5 x 10(10) protons/spill for patient treatment, this system can provide 50 cGy/min for a 20-cm-diam field and 9-cm range modulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Equipment Design↗

A beam intensity monitor for the Loma Linda cancer therapy proton accelerator.

A beam intensity monitor was tested in a 230-MeV proton beam at the Loma Linda Proton Therapy Accelerator during its commissioning at Fermi National Accelerator Laboratory. The intensity monitor was designed to regulate the beam intensity extracted from the proton synchrotron. The proton beam is tunable between 70 and 250 MeV with an adjustable intensity between 10(10) and 10(11) protons per spill. A beam spill is typically 1 s long with a 2-s repetition period. The intensity monitor must be radiation hard, expose minimum mass to the beam, and measure intensity to 1% in 1-ms time intervals. To this end, a 5-cm-thick xenon gas scintillator optically coupled to a photomultiplier tube (PMT) was tested to measure its response to the proton beam. The gas cell was operated at 1.2 atm of pressure and has 12.7-microns-thick titanium entrance and exit foils. The total mass exposed to the beam is 0.14 g/cm2 and is dominated by the titanium windows. This mass corresponds to a range attenuation equal to 1.4 mm of water. The energy lost to the xenon gas is about 70 keV per proton. Each passing proton will produce approximately 2000 photons. With a detection efficiency on the order of 0.05% for this UV light, one would anticipate over 10(10) photoelectrons per second. In a 1-ms time bin there will be approximately 10(7) photoelectrons. This yields a resolution limited by systematics. For unregulated 0.4-s proton spills, we observe a response bandwidth in excess of 10(4) Hz. While signal-to-noise and linearity were not easily measured, we estimate as few as 10(3) protons can be observed suggesting a dynamic range in excess of 10(5) is available.

Humans↗