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Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs.
Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel.
Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy.
Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment.
To fulfil the requirements of ESS on beam transmission and emittance growth a detailed knowledge of the physics of beam formation as well as the interaction of the H- with the residual gas is substantial. Space charge compensated beam transport using solenoids for ion optics is in favour for the Low Energy Beam Transport (LEBT) between ion source and the first RFQ. Space charge compensation reduces the electrical self fields and beam radii and therefore emittance growth due to aberrations and redistribution. Transport of H- near the ion source is negatively influenced by the dipole fields required for beam extraction and e--dumping and the high gas pressure. The destruction of the rotational symmetry together with the space charge forces causes emittance growth and particle losses within the extraction system. High residual gas pressure near the extractor together with the high cross section for stripping will influence the transmission as well as space charge compensation. Therefore a detailed knowledge of the interaction of the residual gas with the beam and the influence of the external fields on the distribution of the compensation particles is necessary to reduce particle losses and emittance growth. Preliminary experiments using positive hydrogen ions for reference already show the influence of dipole fields on beam emittance. First measurements with H- confirm these results. Additional information on the interactions of the residual gas with the beam ions have been gained from the measurements using the momentum and energy analyser.
Investigation of the focus shift due to compensation process for low energy ion beam transport
(2000)
In magnetic Low Energy Beam Transport (LEBT) sections space charge compensation helps to enhance the transportable beam current and to reduce emittance growth due to space charge forces. For pulsed beams the time neccesary to establish space charge compensation is of great interest for beam transport. Particularly with regard to beam injection into the first accelerator section (e.g. RFQ) investigation of effects on shift of the beam focus due to space charge compensation are very important. The achieved results helps to obviate a mismatch into the first RFQ. To investigate the space charge compensation due to residual gas ionization, time resolved measurements using pulsed ion beams were performed at the LEBT system at the IAP and at the CEA-Saclay injektion line. A residual gas ion energy analyser (RGIA) equiped with a channeltron was used to measure the potential destribution as a function of time to estimate the rise time of compensation. For time resolved measurements (delta t min=50ns) of the radial density profile of the ion beam a CCD-camera was applied. The measured data were used in a numerical simulation of selfconsistant eqilibrium states of the beam plasma [1] to determine plasma parameters such as the density, the temperature, the kinetic and potential energy of the compensation electrons as a function of time. Measurements were done using focused proton beams (10keV, 2mA at IAP and 92keV, 62mA at CEA-Saclay) to get a better understanding of the influence of the compensation process. An interpretation of the acquired data and the achieved results will be presented.
High perveance negative ion beams with low emittance are essential for several next generation particle accelerators (i. g. spallation sources like ESS [1] and SNS [2]). The extraction and transport of these beams have intrinsic difficulties different from positive ion beams. Limitation of beam current and emittance growth have to be avoided. To fulfill the requirements of those projects a detailed knowledge of the physics of beam formation the interaction of the H- with the residual gas and transport is substantial. A compact cesium free H- volume source delivering a low energy high perveance beam (6.5 keV, 2.3 mA, perveance K= 0.0034) has been built to study the fundamental physics of beam transport and will be integrated into the existing LEBT section in the near future. First measurements of the interaction between the ion beam and the residual gas will be presented together with the experimental set up and preliminary results.
High perveance negative ion beams with low emittance are essential for several next generation particle accelerators (i. g. spallation sources like ESS [1] and SNS [2]). The extraction and transport of these beams have intrinsic difficulties different from positive ion beams. Limitation of beam current and emittance growth have to be avoided. To fulfill the requirements of those projects a detailed knowledge of the physics of beam formation the interaction of the H- with the residual gas and transport is substantial. A compact cesium free H- volume source delivering a low energy high perveance beam (6.5 keV, 2.3 mA, perveance K= 0.0034) has been built to study the fundamental physics of beam transport and will be integrated into the existing LEBT section in the near future. First measurements of the interaction between the ion beam and the residual gas will be presented together with the experimental set up and preliminary results.
The knowledge of the build up time of space charge compensation (SCC) and the investigation of the compensation process is of main interest for low energy beam transport of pulsed high perveance ion beams under space charge compensated conditions. To investigate experimentally the rise of compensation an LEBT system consisting of a pulsed ion source, two solenoids and a drift tube as diagnostic section has been set up. The beam potential has been measured time resolved by a residual gas ion energy analyser (RGA). A numerical simulation for the calculation of self-consistent equilibrium states of the beam plasma has been developed to determine plasma parameters which are difficult measure directly. The results of the simulation has been compared with the measured data to investigate the behavior of the compensation electrons as a function of time. The acquired data shows that the theoretical rise time of space charge compensation is by a factor of two shorter than the build up time determined experimentally. In view of description the process of SCC an interpretation of the gained results is given.
The determination of the beam emittance using conventional destructive methods suffers from two main disadvantages. The interaction between the ion beam and the measurement device produces a high amount of secondary particles. Those particles interact with the beam and can change the transport properties of the accelerator. Particularly in the low energy section of high current accelerators like proposed for IFMIF, heavy ion inertial fusion devices (HIDIF) and spallation sources (ESS, SNS) the power deposited on the emittance measurement device can lead to extensive heat on the detector itself and can destruct or at least dejust the device (slit or grit for example). CCD camera measurements of the incident light emitted from interaction of beam ions with residual gas are commonly used for determination of the beam emittance. Fast data acquisition and high time resolution are additional features of such a method. Therefore a matrix formalism is used to derive the emittance from the measured profile of the beam [1,2] which does not take space charge effects and emittance growth into account. A new method to derive the phase space distribution of the beam from a single CCD camera image using statistical numerical methods will be presented together with measurements. The results will be compared with measurements gained from a conventional Allison type (slit-slit) emittance measurement device.
For investigation of space charge compensation process due to residual gas ionization and the experimentally study of the rise of compensation, a Low Energy Beam Transport (LEBT) system consisting of an ion source, two solenoids, a decompensation electrode to generate a pulsed decompensated ion beam and a diagnostic section was set up. The potentials at the beam axis and the beam edge were ascertained from time resolved measurements by a residual gas ion energy analyzer. A numerical simulation of self-consistent equilibrium states of the beam plasma has been developed to determine plasma parameters which are difficult to measure directly. The temporal development of the kinetic and potential energy of the compensation electrons has been analyzed by using the numerically gained results of the simulation. To investigate the compensation process the distribution and the losses of the compensation electrons were studied as a function of time. The acquired data show that the theoretical estimated rise time of space charge compensation neglecting electron losses is shorter than the build up time determined experimentally. To describe the process of space charge compensation an interpretation of the achieved results is given.
A LEBT system consisting of an ion source, two solenoids, and a diagnostic section has been set up to investigate the space charge compensation process due to residual gas ionization [1] and to study experimentally the rise of compensation. To gain the radial beam potential distribution time resolved measurements of the residual gas ion energy distribution were carried out using a Hughes Rojanski analyzer [2,3]. To measure the radial density profile of the ion beam a CCD-camera performed time resolved measurements, which allow an estimation the rise time of compensation. Further the dynamic effect of the space charge compensation on the beam transport was shown. A numerical simulation under assumption of selfconsistent states [4] of the beam plasma has been used to determine plasma parameters such as the radial density profile and the temperature of the electrons. The acquired data show that the theoretical estimated rise time of space charge compensation neglecting electron losses is shorter than the build up time determined experimentally. An interpretation of the achieved results is given.
Influence of space charge fluctuations on the low energy beam transport of high current ion beams
(2000)
For future high current ion accelerators like SNS, ESS or IFMIF the beam behaviour in low energy beam transport sections is dominated by space charge forces. Therefore space charge fluctuations (e. g. source noise) can drastically influence the beam transport properties of the low energy beam transport section. Losses of beam ions and emittance growth are the most severe problems. For electrostatic transport systems either a LEBT design has to be found which is insensitive to variations of the space charge or the origin of the fluctuations has to be eliminated. For space charge compensated transport as proposed for ESS and IFMIF the situation is different: No major influence on beam transport is expected for fluctuations below a cut-off frequency given by the production rate of the compensation particles. Above this frequency the fluctuations can not be compensated by particle production alone, but redistributions of the compensation particles helps to compensate the influence of the fluctuations. Above a second cut-off frequency given by the density and the temperature of the compensation particles their redistribution is too slow to reduce the influence of the space charge fluctuations. Transport simulations for the IFMIF injector including space charge fluctuations will be presented together with a determination of the cut-off frequencies. The results will be compared with measurements of the rise time of space charge compensation.
Accelerator Driven Systems (ADS) are promising tools for the efficient transmutation of nuclear waste products in dedicated industrial installations, called transmuters. The Myrrha project at Mol, Belgium, placed itself on the path towards these applications with a multipurpose and versatile system based on a liquid PbBi (LBE) cooled fast reactor (80 MWth) which may be operated in both critical and subcritical modes. In the latter case the core is fed by spallation neutrons obtained from a 600 MeV proton beam hitting the LBE coolant/target. The accelerator providing this beam is a high intensity CW superconducting linac which is laid out for the highest achievable reliability. The combination of a parallel redundant and of a fault tolerant scheme should allow obtaining an MTBF value in excess of 250 hours that is required for optimal integrity and successful operation of the ADS. Myrrha is expected to be operational in 2023. The forthcoming 4-year period is fully dedicated to R&D activities, and in the field of the accelerator they are strongly focused on the reliability aspects and on the proper shaping of the beam trip spectrum.
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.
As the successor of the EUROTRANS project, the MAX project is aiming to continue the R&D effects for a European Accelerator-Driven System and to bring the conceptual design to reality. The layout of the driver linac for MAX will follow the reference design made for the XT-ADS phase of the EUROTRANS project. For the injector part, new design strategies and approaches, e.g. half resonant frequency, half transition-energy between the RFQ and the CH-DTL, and using the 4-rod RFQ structure instead of the originally proposed 4-vane RFQ, have been conceived and studied to reach a more reliable CW operation at reduced costs. In this paper, the design and simulation results of the MAX injector are presented.
The MYRRHA Project (Multi Purpose Hybrid Reactor for High Tech Applications) at Mol/belgium will be a user facility with emphasis on research with neutron generated by a spallation source. One main aspect is the demonstration of nuclear waste technology using an accelerator driven system. A superconducting linac delivers a 4 mA, 600 MeV proton beam. The first accelerating section is covered by the 17 MeV injector. It consists of a proton source, an RFQ, two room temperature CH cavities and 4 superconducting CH-cavities. The initial design has used an RF frequency of 352 MHz. Recently the frequency of the injector has been set to 176 MHz. The main reason is the possible use of a 4-rod-RFQ with reduced power dissipation and energy, respectively. The status of the overall injector layout including cavity design is presented.
EUROTRANS is a European research program for the transmutation of high level nuclear waste in an accelerator-driven system (ADS). As proposed, the driver linac needs to deliver a 2.5–4 mA, 600 MeV continuous-wave (CW) proton beam and later a 20 mA, 800 MeV one to the spallation target in the prototype-scale and industrial-scale demonstration phases, respectively. This paper is focusing on the conceptual studies performed with respect to the 17 MeV injector. First, the special beam dynamics strategies and methods, which have been developed and applied to design a current-variable injector up to 30 mA for allowing an easy upgrade without additional R&D costs, will be introduced. Then the error study made for evaluating the tolerance limits of the designed injector will be presented as well.
MYRRHA is conceived as an accelerator driven system (ADS) for transmutation of high level nuclear waste. The neutron source is created by coupling a proton accelerator of 600 MeV with a 4 mA proton beam, a spallation source and a sub-critical core. The IAP of Frankfurt University is responsible for the development of the 17 MeV injector operated at 176 MHz. The injector consists of a 1.5 MeV 4-Rod-RFQ and six CH-drifttube-structures. The first two CH-structures will be operated at room temperature and the other CH-structures are superconducting cavities assembled in one cryo-module. To achieve the extremely high reliability required by the ADS application, the design of the 17 MeV injector has been intensively studied, with respect to thermal issues, minimum peak fields and field distribution.
Metasomatic reaction zones between mafic and ultramafic rocks exhumed from subduction zones provide a window into mass-transfer processes at high pressure. However, accurate interpretation of the rock record requires distinguishing high-pressure metasomatic processes from inherited oceanic signatures prior to subduction. We integrated constraints from bulk-rock geochemical compositions and petrophysical properties, mineral chemistry, and thermodynamic modeling to understand the formation of reaction zones between juxtaposed metagabbro and serpentinite as exemplified by the Voltri Massif (Ligurian Alps, Italy). Distinct zones of variably metasomatized metagabbro are dominated by chlorite, amphibole, clinopyroxene, epidote, rutile, ilmenite, and titanite between serpentinite and eclogitic metagabbro. Whereas the precursor serpentinite and oxide gabbro formed and were likely already in contact in an oceanic setting, the reaction zones formed by diffusional Mg-metasomatism between the two rocks from prograde to peak, to retrograde conditions in a subduction zone. Metasomatism of mafic rocks by Mg-rich fluids that previously equilibrated with serpentinite could be widespread along the subduction interface, within the subducted slab, and the mantle wedge. Furthermore, the models predict that talc formation by Si-metasomatism of serpentinite in subduction zones is limited by pressure-dependent increase in the silica activity buffered by the serpentine-talc equilibrium. Elevated activities of aqueous Ca and Al species would also favor the formation of chlorite and garnet. Accordingly, unusual conditions or processes would be required to stabilize abundant talc at high P-T conditions. Alternatively, a different set of mineral assemblages, such as serpentine- or chlorite-rich rocks, may be controlling the coupling-decoupling transition of the plate interface.
Talc formation via silica-metasomatism of ultramafic rocks is believed to play key roles in subduction zone processes. Yet, the conditions of talc formation remain poorly constrained. We used thermodynamic reaction-path models to assess the formation of talc at the slab-mantle interface and show that it is restricted to a limited set of pressure–temperature conditions, protolith, and fluid compositions. In contrast, our models predict that chlorite formation is ubiquitous at conditions relevant to the slab-mantle interface of subduction zones. The scarcity of talc and abundance of chlorite is evident in the rock record of exhumed subduction zone terranes. Talc formation during Si-metasomatism may thus play a more limited role in volatile cycling, strain localization, and in controlling the decoupling-coupling transition of the plate interface. Conversely, the observed and predicted ubiquity of chlorite corroborates its prominent role in slab-mantle interface processes that previous studies attributed to talc.
Key Points:
Limited talc formation by Si-metasomatism of ultramafic rocks in subduction zones
Chlorite formation is likely pervasive at the slab-mantle interface
Preferential formation of chlorite has wide-ranging chemical and physical implications for subduction zone processes
Plain Language Summary: In subduction zones, talc can form during chemical reactions of mantle rocks with silica-enriched fluids at the interface between descending oceanic plates and the overriding mantle. Its formation and distribution in subduction zones are believed to affect the volatile budget, rheological properties, and the down-dip limit of the decoupling of the slab-mantle interface. Therefore, illuminating the conditions that facilitate talc formation at high pressure-temperature conditions is key in assessing its roles in fundamental subduction zone processes. Using thermodynamic reaction-path models, we show that the formation of talc at the slab-mantle interface is restricted to a limited set of environmental conditions, because its formation is highly sensitive to the compositions of the mantle rocks and reactant fluids. Contrary to common belief, talc is unlikely to form in high abundance in ultramafic rocks metasomatized by Si-rich slab-derived fluids. Rather, our models predict the ubiquitous formation of chlorite along with other silicate minerals during Si-metasomatism due to the competing effects from other dissolved components that favor their formation over talc. This study calls into question the importance of talc during Si-metasomatism in subduction zones but highlights the more predominant role of chlorite.
Le concept d’eurocompréhension signifie intercompréhension dans les trois grands groupes linguistiques européens, à savoir les langues romanes, slaves et germaniques. Il s’agit, en respectant les objectifs1 de la politique linguistique de l’Union Européenne, de parvenir de façon modulaire au plurilinguisme par le biais de compétences réceptives. Dans ce cadre, les recherches linguistiques effectuées sur l’intercompréhension fournissent les bases de transfert interlangues pour l’exploitation cognitive de la parenté entre les langues des groupes différents. ...