A combined approach for the calculation of activation yields and the characterization of materials for a medical cyclotron.

Cyclotrons for the production of radiopharmaceuticals have become important tools in modern nuclear medicine. At the end of their lifecycles, such installations have to be dismantled and any activated materials must be treated according to the local radiation protection legislation. Using a simulation model, we have developed a non-destructive approach for the radiological characterization of components inside and around an IBA Cyclone 18/9 cyclotron. The methodology is based on software tools developed at CERN (FLUKA Monte Carlo code, ActiWiz and RAW). The simulation results were compared to measurements made using reference samples placed around the cyclotron inside the bunker. Results show a reasonable agreement between simulation and measurements of about a factor of two for a set of 27 reference samples and 11 radionuclides of interest. The origin of this factor has been thoroughly evaluated and opened the door to further investigations leading to possible avenues for improvement.

SOLIDUSS: Solid-state diffusion software for radiation protection.

The out-diffusion of radionuclides from activated material in case of a fire may represent a non-negligible contribution to the radiological source term of such an event. In order to assess the contribution of this phenomenon, a software package has been designed and implemented. In the present document we briefly introduce the numerical treatment used to tackle the problem prior to the explanation of the software's logic. The document ends with an exemplary simulation and a study carried out to validate the implementation of the algorithm. The presented tool has been named SOLIDUSS, it is mainly written in C++ and uses a Monte Carlo based approach to simulate the diffusion of radioisotopes within solid materials. It is designed to run coupled with CERN-FLUKA, taking advantage of its geometry kernel to carry out diffusion calculations in arbitrarily complex geometries. The user can provide 3D temperature maps along with many other parameters that allow the program to target a wide range of different scenarios. As results SOLIDUSS provides 3D radionuclide concentration maps as well as the amount of radionuclides out-diffused from the selected materials. So far, this software has undergone numerical validation which will be discussed in this paper. Benchmarking against experimental data is currently ongoing.

Lower or Higher Oxygenation Targets for Acute Hypoxemic Respiratory Failure.

BACKGROUND: Patients with acute hypoxemic respiratory failure in the intensive care unit (ICU) are treated with supplemental oxygen, but the benefits and harms of different oxygenation targets are unclear. We hypothesized that using a lower target for partial pressure of arterial oxygen (Pao2) would result in lower mortality than using a higher target. METHODS: In this multicenter trial, we randomly assigned 2928 adult patients who had recently been admitted to the ICU (≤12 hours before randomization) and who were receiving at least 10 liters of oxygen per minute in an open system or had a fraction of inspired oxygen of at least 0.50 in a closed system to receive oxygen therapy targeting a Pao2 of either 60 mm Hg (lower-oxygenation group) or 90 mm Hg (higher-oxygenation group) for a maximum of 90 days. The primary outcome was death within 90 days. RESULTS: At 90 days, 618 of 1441 patients (42.9%) in the lower-oxygenation group and 613 of 1447 patients (42.4%) in the higher-oxygenation group had died (adjusted risk ratio, 1.02; 95% confidence interval, 0.94 to 1.11; P = 0.64). At 90 days, there was no significant between-group difference in the percentage of days that patients were alive without life support or in the percentage of days they were alive after hospital discharge. The percentages of patients who had new episodes of shock, myocardial ischemia, ischemic stroke, or intestinal ischemia were similar in the two groups (P = 0.24). CONCLUSIONS: Among adult patients with acute hypoxemic respiratory failure in the ICU, a lower oxygenation target did not result in lower mortality than a higher target at 90 days. (Funded by the Innovation Fund Denmark and others; HOT-ICU ClinicalTrials.gov number, NCT03174002.).

Detailed study of the distribution of activation inside the magnet coils of a compact PET cyclotron.

We determined the distribution of activation products inside the magnet coils of a medical cyclotron that has been operational for fifteen years. Besides FLUKA, we based our approach on new software tools (RAW and ActiWiz) developed for high-energy accelerators at CERN. A combined analysis of measurements on the coils with Monte-Carlo simulations resulted in a detailed three-dimensional radiological characterisation of the coils. Our results provide the required information for the radiation protection expert to identify the appropriate waste elimination scheme.

[Perioperative infusion therapy in children : Are infusion sets with precision flow regulators suitable for pediatric anesthesia?] / Perioperative Infusionstherapie im Kindesalter : Eignen sich Infusionssysteme mit Laufratenbeschränkung für die Kinderanästhesie?

BACKGROUND: Infusion sets with precision flow regulators are frequently used in children undergoing surgery in order to control the perioperative administration of fluids. There are no data about the safety and accuracy of these infusion sets. A study was therefore conducted to compare adjusted and actual flow rates of three different infusion sets with precision flow regulators under standardized conditions. METHODS: The study evaluated three different infusion sets with precision flow regulators each at two different static levels. The actual flow rates of 5 infusions were recorded each time for adjusted flow rates of 50 ml/h, 100 ml/h, 150 ml/h, 200 ml/h and 250 ml/h over 1 h. Statistical analysis was performed with Excel (Excel, Microsoft Corporation, Redmond, WA, USA) and SOFA (Paton-Simpson and Associates Ltd., USA). The results are presented as means (standard deviation). RESULTS: For the adjusted flow rates of 50, 100, 150, 200 and 250 ml/h, actual flow rates were 107 (5.3), 174.8 (6.5), 255.8 (10.2), 312.4 (15.7) and 362.6 (20.2) ml/h for the Frekadrop® infusion set at a static level of 128 cm and 83.8 (4.4), 147.8 (5.5), 197 (12.4), 257.2 (4.97) and 311.6 (17.9) ml/h at a static level of 100 cm, respectively. For the Exadrop® infusion set actual flow rates were 88.6 (6.9), 131.2 (14.1), 224.4 (14.1), 296.6 (27.6) and 330.4 (22.4) ml/h at a static level of 128 cm and 54 (4), 82.4 (10.2), 138.8 (15.7), 209.4 (36.8) and 249 (12) ml/h at a static level of 76 cm, respectively. For the D-Flo infusion set actual flow rates were 95.6 (2.8), 167.6 (29), 217.8 (9.9), 281.6 (10.6) and 396.8 (37.5) ml/h at a static level of 128 cm and 69.2 (4.4), 110.2 (12.6), 169.2 (6), 205.2 (14) and 243 (15.9) ml/h at a static level of 80 cm, respectively. CONCLUSION: The actual flow rates differed considerably from the adjusted flow rates in the evaluated infusion sets. The flow rates substantially depended on the static level of the infusion. First and foremost, regulation of the administered infusion volume does not seem to be reliable when using an infusion set with a precision flow regulator.

The influence of the type of filling gas on the response of ionisation chambers to a mixed high-energy radiation field.

Radiation protection dosimetry in radiation fields behind the shielding of high-energy accelerators such as CERN is a challenging task and the quantitative understanding of the detector response used for dosimetry is essential. Measurements with ionisation chambers are a standard method to determine absorbed dose (in the detector material). For applications in mixed radiation fields, ionisation chambers are often also calibrated in terms of ambient dose equivalent at conventional reference radiation fields. The response of a given ionisation chamber to the various particle types of a complex high-energy radiation field in terms of ambient dose equivalent depends of course on the materials used for the construction and the chamber gas used. This paper will present results of computational studies simulating the exposure of high-pressure ionisation chambers filled with different types of gases to the radiation field at CERN's CERN-EU high-energy reference field facility. At this facility complex high-energy radiation fields, similar to those produced by cosmic rays at flight altitudes, are produced. The particle fluence and spectra calculated with FLUKA Monte Carlo simulations have been benchmarked in several measurements. The results can be used to optimise the response of ionisation chambers for the measurement of ambient dose equivalent in high-energy mixed radiation fields.

Field calibration studies for ionisation chambers in mixed high-energy radiation fields.

The monitoring of ambient doses at work places around high-energy accelerators is a challenging task due the complexity of the mixed stray radiation fields encountered. At CERN, mainly Centronics IG5 high-pressure ionisation chambers are used to monitor radiation exposure in mixed fields. The monitors are calibrated in the operational quantity ambient dose equivalent H*(10) using standard, source-generated photon- and neutron fields. However, the relationship between ionisation chamber reading and ambient dose equivalent in a mixed high-energy radiation field can only be assessed if the spectral response to every component and the field composition is known. Therefore, comprehensive studies were performed at the CERN-EU high-energy reference field facility where the spectral fluence for each particle type has been assessed with Monte Carlo simulations. Moreover, studies have been performed in an accessible controlled radiation area in the vicinity of a beam loss point of CERN's proton synchrotron. The comparison of measurements and calculations has shown reasonable agreement for most exposure conditions. The results indicate that conventionally calibrated ionisation chambers can give satisfactory response in terms of ambient dose equivalent in stray radiation fields at high-energy accelerators in many cases. These studies are one step towards establishing a method of 'field calibration' of radiation protection instruments in which Monte Carlo simulations will be used to establish a correct correlation between the response of specific detectors to a given high-energy radiation field.

Response of neutron detectors to high-energy mixed radiation fields.

Radiation protection around CERN's high-energy accelerators represents a major challenge due to the presence of complex, mixed radiation fields. Behind thick shielding neutrons dominate and their energy ranges from fractions of eV to about 1 GeV. In this work the response of various portable detectors sensitive to neutrons was studied at CERN's High-Energy Reference Field Facility (CERF). The measurements were carried out with conventional rem counters, which usually cover neutron energies up to 20 MeV, the Thermo WENDI-2, which is specified to measure neutrons up to several GeV, and a tissue-equivalent proportional counter. The experimentally determined neutron dose equivalent results were compared with Monte Carlo (MC) simulations. Based on these studies field calibration factors can be determined, which result in a more reliable estimate of H*(10) in an unknown, but presumably similar high-energy field around an accelerator than a calibration factor determined in a radiation field of a reference neutron source.

Response of alanine and radio-photo-luminescence dosemeters to mixed high-energy radiation fields.

Alanine and Radio-Photo-Luminescence (RPL) dosemeters are passive dosemeters used to monitor absorbed dose in all kind of radiation fields. However, up to now both dosemeter types are calibrated to photon sources only. In order to study the response of RPL and alanine dosemeters to mixed high-energy particle fields like those occurring at CERN's accelerators, an irradiation campaign at the CERN-EC High-Energy Reference field Facility (CERF-field) was performed. In this facility a copper target is irradiated by hadrons with a momentum of 120 GeV/c. Dosemeters were exposed to various mixed radiation fields by placing them at various positions on the surface of the target. In addition to the experiment FLUKA Monte Carlo simulations were carried out, which provide information concerning the energy deposition at the dosemeter locations. This paper compares the measurements with the simulation results and discusses the radiation field compositions present at the various dosemeter positions on the target.

[Shock wave treatment for tennis elbow]. / Stosswellentherapie bei Tennisellenbogen Literaturüberblick.

Randomized controlled trials were evaluated to assess the effectiveness of extracorporeal shock wave treatment in the management of tennis elbow. Five trials had a mediocre methodology and four trials had a high-quality design. Well-designed randomized control trials have provided evidence of the effectiveness of shock wave intervention for tennis elbow.

Characterisation of ionisation chambers for a mixed radiation field and investigation of their suitability as radiation monitors for the LHC.

Monitoring of the radiation environment is one of the key tasks in operating a high-energy accelerator such as the Large Hadron Collider (LHC). The radiation fields consist of neutrons, charged hadrons as well as photons and electrons with energy spectra extending from those of thermal neutrons up to several hundreds of GeV. The requirements for measuring the dose equivalent in such a field are different from standard uses and it is thus necessary to investigate the response of monitoring devices thoroughly before the implementation of a monitoring system can be conducted. For the LHC, it is currently foreseen to install argon- and hydrogen-filled high-pressure ionisation chambers as radiation monitors of mixed fields. So far their response to these fields was poorly understood and, therefore, further investigation was necessary to prove that they can serve their function well enough. In this study, ionisation chambers of type IG5 (Centronic Ltd) were characterised by simulating their response functions by means of detailed FLUKA calculations as well as by calibration measurements for photons and neutrons at fixed energies. The latter results were used to obtain a better understanding and validation of the FLUKA simulations. Tests were also conducted at the CERF facility at CERN in order to compare the results with simulations of the response in a mixed radiation field. It is demonstrated that these detectors can be characterised sufficiently enough to serve their function as radiation monitors for the LHC.

[Evidence-based evaluation of present guidelines for the treatment of tennis elbow -- a review]. / Evidenz-basierte Uberprüfung der Therapieempfehlungen bei Epicondylopathia humeri lateralis (Tennisellenbogen) -- eine Ubersicht.

The guidelines of the German Orthopaedic Societies regarding the treatment of lateral elbow epicondylitis were analysed on the ground of recently published reviews or randomised placebo-controlled trials (RCT). For the acute phase, reviews or RCTs failed to show a clinical effect beyond placebo if follow-up was extended over 6 weeks. For the chronic phase a current Cochrane review failed to identify any controlled trial regarding surgical procedures during the last decades. Without an adequate control group, it is not possible to draw any meaningful conclusions about the value of this modality of treatment. Therefore surgery is not indicated before repetitive low-energy extracorporeal shock wave therapy (ESWT) has been applied. This novel treatment, under strictly standardized conditions, showed effects beyond placebo in independent randomised placebo-controlled trials for follow-up periods of 3 and 6 months. To date there exists no evidence-based therapeutic algorithm for the treatment of acute and chronic tennis elbow. Even medium-term effects should be regarded as either a placebo effect or natural regression to the mean.

High-energy extracorporeal shock wave treatment of nonunions.

Forty-three consecutive patients who did not have healing of tibial or femoral diaphyseal and metaphyseal fractures and osteotomies for at least 9 months after injury or surgery were examined prospectively for use of high-energy extracorporeal shock waves. Former treatment modalities (cast, external fixator, plate osteosynthesis, limitation of weightbearing) remained unchanged. In all cases a 99mTechnetium dicarboxyphosphonate regional two-phase bone scintigraphy was performed before one treatment with 3,000 impulses of an energy flux density of 0.6 mJ/mm2. Radiologic and clinical followups were done at 4-week intervals starting 8 weeks after shock wave treatment. The success criterion was bridging of all four cortices in the anteroposterior and lateral radiographic views, in oblique views, or by conventional tomography. An independent observer described bony consolidation in 31 of 43 cases (72%) after an average of 4 months (range, 2-7 months). Twenty-nine of 35 (82.9%) patients with a positive bone scan had healing of the pseudarthrosis compared with two of eight (25%) patients with a negative bone scan. Six of these eight patients with negative scans were heavy smokers. No complications were observed. High-energy shock wave therapy seemed to be an effective noninvasive tool for stimulation of bone healing in properly selected patients with a diaphyseal or metaphyseal nonunion of the femur or tibia. Additional controlled studies are mandatory.

Test of molecular mode coupling theory for general rigid molecules

We report recent progress on the test of mode coupling theory for molecular liquids (MMCT) for molecules of arbitrary shape. The MMCT equations in the long time limit are solved for supercooled water including all molecular degrees of freedom. In contrast to our earlier treatment of water as a linear molecule, we find that the glass-transition temperature T(c) is overestimated by the theory as was found in the case of simple liquids. The nonergodicity parameters are calculated from the "full" set of MMCT equations truncated at l(co)=2. These results are compared (i) with the nonergodicity parameters from MMCT with l(co)=2 in the "dipole" approximation n=n(')=0 and the diagonalization approximation n=n(')=0, l=l(') and (ii) with the corresponding results from a MD simulation. This work supports the possibility that a reduction to the most prominent correlators may constitute a valid approximation for solving the MMCT equations for rigid molecules.

Molecular correlations in a supercooled liquid

We present static and dynamic properties of molecular correlation functions S(lmn,l(')m(')n('))(q-->,t) in a simulated supercooled liquid of water molecules, as a preliminary effort in the direction of solving the molecular mode-coupling theory (MMCT) equations for supercooled molecular liquids. The temperature and time dependence of various molecular correlation functions, calculated from 250 ns long molecular dynamics simulations, show the characteristic patterns predicted by MMCT and shed light on the driving mechanism responsible for the slowing down of the molecular dynamics. We also discuss the symmetry properties of the molecular correlation functions that can be predicted on the basis of the C(2v) symmetry of the molecule. Analysis of the molecular dynamics results for the static correlators S(lmn,l(')m(')n('))(q-->) reveals that additional relationships between correlators with different signs of n and n(') exist. We prove that for molecules with C(rv) symmetry this unexpected result becomes exact at least for high temperatures.

Molecular mode-coupling theory applied to a liquid of diatomic molecules

We study the molecular mode-coupling theory for a liquid of diatomic molecules. The equations for the critical tensorial nonergodicity parameters F(m)(ll('))(q) and the critical amplitudes of the beta relaxation H(m)(ll('))(q) are solved up to a cutoff l(co)=2 without any further approximations. Here l,m are indices of spherical harmonics. Contrary to previous studies, where additional approximations were applied, we find in agreement with simulations that all molecular degrees of freedom vitrify at a single temperature T(c). The theoretical results for the nonergodicity parameters and the critical amplitudes are compared with those from simulations. The qualitative agreement is good for all molecular degrees of freedom. To study the influence of the cutoff on the nonergodicity parameter, we also calculate the nonergodicity parameters for an upper cutoff l(co)=4. In addition, we also propose a method for the calculation of the critical nonergodicity parameter from the liquid side of transition.

Neutron scattering and molecular correlations in a supercooled liquid.

We show that the intermediate scattering function S(n)(q,t) for neutron scattering (ns) can be expanded naturally with respect to a set of molecular correlation functions that give a complete description of the translational and orientational two-point correlations in the liquid. The general properties of this expansion are discussed with special focus on the q dependence, and hints for a (partial) determination of the molecular correlation functions from neutron scattering results are given. The resulting representation of the static structure factor S(n)(q) is studied in detail for a model system using data from a molecular dynamics simulation of a supercooled liquid of rigid diatomic molecules. The comparison between the exact result for S(n)(q) and different approximations that result from a truncation of the series representation demonstrates its good convergence for the given model system. On the other hand it shows explicitly that the coupling between translational and orientational degrees of freedom of each molecule and rotational motion of different molecules cannot be neglected in the supercooled regime. Further we report the existence of a prepeak in the ns static structure factor of the examined fragile glass former, demonstrating that prepeaks can occur even in the most simple molecular liquids. Besides examining the dependence of the prepeak on the scattering length and the temperature we use the expansion of S(n)(q) into molecular correlation functions to point out the intermediate range orientational order as its principle origin.

Molecular mode-coupling theory for supercooled liquids: application to water.

We present mode-coupling equations for the description of the slow dynamics observed in supercooled molecular liquids close to the glass transition. The mode-coupling theory (MCT) originally formulated to study the slow relaxation in simple atomic liquids, and then extended to the analysis of liquids composed by linear molecules, is here generalized to systems of arbitrarily shaped, rigid molecules. We compare the predictions of the theory for the q-vector dependence of the molecular nonergodicity parameters, calculated by solving numerically the molecular MCT equations in two different approximation schemes, with "exact" results calculated from a molecular dynamics simulation of supercooled water. The agreement between theory and simulation data supports the view that MCT succeeds in describing the dynamics of supercooled molecular liquids, even for network forming ones.

Expression of nuclear lectin carbohydrate-binding protein 35 in human immunodeficiency virus type 1-infected Molt-3 cells.

The nuclear carbohydrate-binding protein 35 (CBP35), a beta-galactoside-specific lectin with an M(r) of 35,000, has been identified in nuclear ribonucleoprotein complexes (RNPs) from a variety of mammalian tissues and cells. Here we determined that the expression of CBP35 mRNA greatly increases after infection of Molt-3 cells with human immunodeficiency virus type 1 (HIV-1), concomitantly with the onset of expression of the viral regulatory gene tat, and then declines. The increase in CBP35 mRNA level results in an enhanced synthesis of CBP35, as evidenced in nitrocellulose filter binding assay using radiolabeled, sugar-specific neoglycoprotein. Immunoblotting experiments showed that CBP35 is present in the 40S heterogeneous nuclear RNP complex from HIV-1-infected Molt-3 cells. CBP35 could also be detected using a novel photoreactive alpha-D-galactose probe designed for the specific detection of CBP.