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Giant negative ion sources for neutral beam injectors deliver huge negative ion currents, thanks to their multi-beamlet configuration. As the single-beamlet optics defines the transmission losses along the beamline, the extraction of a similar current for all beamlets is extremely desirable, in order to facilitate the beam source operation (i.e., around perveance match). This Review investigates the correlation between the vertical profile of beam intensity and the vertical profiles of plasma properties at the extraction region of the source, focusing on the influence of increasing cesium injection. Only by the combined use of all available source diagnostics, described in this Review, can beam features on the scale of the non-uniformities be investigated with a sufficient space resolution. At RF power of 50 kW/driver, with intermediate bias currents and a filter field of 2.4 mT, it is found that the central part of the four vertical beam segments exhibits comparable plasma density and beamlet currents; at the edges of the central segments, both the beam and electron density appear to decrease (probably maintaining fixed electron-to-ion ratio); at the bottom of the source, an increase of cesium injection can compensate for the vertical drifts that cause a much higher presence of electrons and a lower amount of negative ions.
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About 10% of all ovarian cancers are due to BRCA 1 and/or BRCA 2 mutations. Some studies have shown that patients belonging to this group have a better survival compared to sporadic groups but data are still inconclusive. The aim of this study was to investigate overall survival in patients with ovarian cancer and germ-line mutations in the BRCA1/2 genes in comparison to high-risk patients, defined as patients with ovarian cancer and a strong family history of breast and ovarian cancer, but who tested negative for the BRCA mutation. We collected all the clinical features and did follow-up. The two groups showed similar characteristics concerning age at diagnosis, histological type and stage. Grade 3 was more frequent in the BRCA group. Survival data did not show any advantage for the BRCA mutated group.
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Proteína BRCA2 , Neoplasias de la Mama/epidemiología , Genes BRCA1 , Predisposición Genética a la Enfermedad/epidemiología , Neoplasias Ováricas/epidemiología , Adulto , Edad de Inicio , Anciano , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Estudios de Casos y Controles , Femenino , Humanos , Incidencia , Italia , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
The requirements of ITER neutral beam injectors (1 MeV, 40 A negative deuterium ion current for 1 h) have never been simultaneously attained; therefore, a dedicated Neutral Beam Test Facility (NBTF) was set up at Consorzio RFX (Padova, Italy). The NBTF includes two experiments: SPIDER (Source for the Production of Ions of Deuterium Extracted from Rf plasma), the full-scale prototype of the source of ITER injectors, with a 100 keV accelerator, to investigate and optimize the properties of the ion source; and MITICA, the full-scale prototype of the entire injector, devoted to the issues related to the accelerator, including voltage holding at low gas pressure. The present paper gives an account of the status of the procurements, of the timeline, and of the voltage holding tests and experiments for MITICA. As for SPIDER, the first year of operation is described, regarding the solution of some issues connected with the radiofrequency power, the source operation, and the characterization of the first negative ion beam.
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Injection of high energy neutral beam particles will be used in the ITER experiment for plasma heating and current drive. In a ITER heating beam injector, a 40 MW electrostatically accelerated negative beam will be neutralised and filtered along the beamline, obtaining a nominal 16.5 MW neutral beam power to be injected in the tokamak plasma or intercepted during conditioning and commissioning. The beam will heat the actively cooled panels of the beamline components with up to 13 MW/m2 surface power density and 18 MW power. These extreme conditions require testing in a ITER full scale neutral beam test facility under construction in Padova where the temperature of the beamline components will be monitored by 610 embedded thermocouples for protection against critical conditions, for recognising beam conditioning, and for deriving beam parameters. Power density maps of the expected beam-component interactions are applied on a parametric non-linear finite element model to simulate fields of expected temperatures. Such thermal maps are analyzed to derive the beam parameters during operation: divergence of 3-7 mrad and misalignment of 0-3 mrad. The sensibility of the temperature measurements is discussed considering a minimum 10% fraction of the nominal beam power.
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BACKGROUND: BRCA1 and BRCA2 are the two major genes responsible for the breast and ovarian cancers that cluster in families with a genetically determined predisposition. However, regardless of the mutation detection method employed, the percentage of families without identifiable alterations of these genes exceeds 50%, even when applying stringent criteria for family selection. A small but significant increase in mutation detection rate has resulted from the discovery of large genomic alterations in BRCA1. A few studies have addressed the question of whether BRCA2 might be inactivated by the same kinds of alteration, but most were either done on a relatively small number of samples or employed cumbersome mutation detection methods of variable sensitivity. OBJECTIVE: To analyse 121 highly selected families using the recently available BRCA2 multiplex ligation dependent probe amplification (MLPA) technique. RESULTS: Three different large genomic deletions were identified and confirmed by analysis of the mutant transcript and genomic characterisation of the breakpoints. CONCLUSIONS: Contrary to initial suggestions, the presence of BRCA2 genomic rearrangements is worth investigating in high risk breast or ovarian cancer families.
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Proteína BRCA2/genética , Neoplasias de la Mama/genética , Eliminación de Gen , Pruebas Genéticas/métodos , Genoma , Neoplasias de la Mama/metabolismo , Clonación Molecular , Análisis Mutacional de ADN , Exones , Femenino , Predisposición Genética a la Enfermedad , Humanos , Modelos Genéticos , Datos de Secuencia Molecular , Recombinación GenéticaRESUMEN
The prototype radio frequency source of the ITER heating neutral beams will be first tested in SPIDER test facility to optimize H- production, cesium dynamics, and overall plasma characteristics. Several diagnostics will allow to fully characterise the beam in terms of uniformity and divergence and the source, besides supporting a safe and controlled operation. In particular, thermal measurements will be used for beam monitoring and system protection. SPIDER will be instrumented with mineral insulated cable thermocouples, both on the grids, on other components of the beam source, and on the rear side of the beam dump water cooled elements. This paper deals with the final design and the technical specification of the thermal sensor diagnostic for SPIDER. In particular the layout of the diagnostic, together with the sensors distribution in the different components, the cables routing and the conditioning and acquisition cubicles are described.
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The beam power produced by the negative ion source for the production of ion of deuterium extracted from RF plasma is mainly absorbed by the beam dump component which has been designed also for measuring the temperatures on the dumping panels for beam diagnostics. A finite element code has been developed to characterize, by thermo-hydraulic analysis, the sensitivity of the beam dump to the different beam parameters. The results prove the capability of diagnosing the beam divergence and the horizontal misalignment, while the entity of the halo fraction appears hardly detectable without considering the other foreseen diagnostics like tomography and beam emission spectroscopy.
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Megavolt ITER Injector Concept Advancement is the full scale prototype of the heating and current drive neutral beam injectors for ITER, to be built at Consorzio RFX (Padova). The engineering design of its components is challenging: the total heat loads they will be subjected to (expected between 2 and 19 MW), the high heat fluxes (up to 20 MW/m(2)), and the beam pulse duration up to 1 h, set demanding requirements for reliable active cooling circuits. In support of the design, the thermo-hydraulic behavior of each cooling circuit under steady state condition has been investigated by using one-dimensional models. The final results, obtained considering a number of optimizations for the cooling circuits, show that all the requirements in terms of flow rate, temperature, and pressure drop are properly fulfilled.
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Megavolt ITER Injector and Concept Advancement, the full-scale prototype of ITER neutral beam injector, is under construction in Italy. The device will generate deuterium negative ions, then accelerated and neutralized. The emerging beam, after removal of residual ions, will be dumped onto a calorimeter. The presence of plasma and its parameters will be monitored in the components of the beam-line, by means of specific electrostatic probes. Double probes, with the possibility to be configured as Langmuir probes and provide local ion density and electron temperature measurements, will be employed in the neutralizer and in the residual ion dump. Biased electrodes collecting secondary emission electrons will be installed in the calorimeter with the aim to provide a horizontal profile of the beam.
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Embedded sensors have been designed for installation on the components of the MITICA beamline, the prototype ITER neutral beam injector (Megavolt ITER Injector and Concept Advancement), to derive characteristics of the particle beam and to monitor the component conditions during operation for protection and thermal control. Along the beamline, the components interacting with the particle beam are the neutralizer, the residual ion dump, and the calorimeter. The design and the positioning of sensors on each component have been developed considering the expected beam-surface interaction including non-ideal and off-normal conditions. The arrangement of the following instrumentation is presented: thermal sensors, strain gages, electrostatic probes including secondary emission detectors, grounding shunt for electrical currents, and accelerometers.
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This paper presents the results of numerical simulations and experimental tests carried out to assess the feasibility and suitability of graphite castellated tiles as beam-facing component in the diagnostic calorimeter of the negative ion source SPIDER (Source for Production of Ions of Deuterium Extracted from Radio frequency plasma). The results indicate that this concept could be a reliable, although less performing, alternative for the present design based on carbon fiber composite tiles, as it provides thermal measurements on the required spatial scale.
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The megavolt ITER injector and concept advancement experiment is the prototype and the test bed of the ITER heating and current drive neutral beam injectors, currently in the final design phase, in view of the installation in Padova Research on Injector Megavolt Accelerated facility in Padova, Italy. The beam source is the key component of the system, as its goal is the generation of the 1 MeV accelerated beam of deuterium or hydrogen negative ions. This paper presents the highlights of the latest developments for the finalization of the MITICA beam source design, together with a description of the most recent analyses and R&D activities carried out in support of the design.
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This study analyses the health related quality of life (HRQOL) of advanced melanoma patients, in a randomised trial comparing bio-chemotherapy (bio-CT) versus chemotherapy (CT). The trial enrolled 178 patients and the median survival was not statistically different between the two arms. HRQOL was assessed at baseline and before each cycle of therapy, using the Rotterdam Symptom Checklist (RSCL) questionnaire completed with 140 patients. At baseline, overall quality of life and psychological distress scores were the most impaired, compared with the normal population. During treatment, the difference between the two arms in the changes from baseline was statistically significant (P=0.03) only in the overall quality of life score, with a decrease of 6.28 points in the bio-CT arm. The mean values decreased significantly in all domains in bio-CT arm, but only in activity level and physical symptom distress scores in the CT arm. Testing HRQOL variables and prognostic clinical factors in a Cox model, only the serum level of lactic dehydrogenase, baseline overall quality of life and the physical symptom distress scores remained significant independent prognostic factors for survival. A score of less than 75 points in the overall quality of life and in the physical symptom distress domains was associated with a Hazard Ratio (HR) of 2.31 (95% Confidence Interval (CI): 1.09-4.90) and 1.92 (95% CI: 1.10-3.36), respectively.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Melanoma/tratamiento farmacológico , Calidad de Vida , Neoplasias Cutáneas/tratamiento farmacológico , Adulto , Anciano , Carmustina/administración & dosificación , Cisplatino/administración & dosificación , Dacarbazina/administración & dosificación , Femenino , Humanos , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Interleucina-2/administración & dosificación , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Proteínas RecombinantesRESUMEN
PURPOSE: To evaluate the maximum tolerated doses (MTD) of ifosfamide when given as a continuous infusion and in combination with fixed doses of bolus 4'-epidoxorubicin in advanced previously untreated adult soft tissue sarcoma patients. METHODS: Treatment consisted of epidoxorubicin, 60 mg/m2 days one and two, and ifosfamide, 1.5 g/m2 every 12 hrs as a 72-hr infusion, at the first level. Further levels of ifosfamide were defined as increments of 12 hrs of the same infusion program. G-CSF 300 microg/die was administered from days +7 to +14. Dose-limiting toxicity (DLT) was defined as: G4 leukopenia or thrombocytopenia of > or =5 days; any G3 neuro or nephrotoxicity; G4 toxicity of any kind. Patients had to complete at least 2 consecutive cycles, and MTD was defined as the level in which 20% of patients developed a DLT; 10-15 patients were entered in each level. RESULTS: First level: overall, 13 patients entered, 3 were not assessable for MTD, and only one developed a DLT. Second level: 18 patients entered, 3 were not assessable for MTD. Hematologic DLT was observed in 3/15 assessable patients. Therefore, the MTD was found at the ifosfamide level of 10.5 g/m2 given in 84 hrs. Eight patients of 29 assessable for response achieved an objective response: 1 complete and 7 partial. The overall response rate was 28% (95% CI: 13-47%). CONCLUSIONS: If we accept 4-day G4 leukopenia as a reliable cutoff for safety, ifosfamide intensification cannot be substantially exploited over already available schedules with the combination of ifosfamide and anthracyclines.
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Antibióticos Antineoplásicos/administración & dosificación , Antineoplásicos Alquilantes/administración & dosificación , Epirrubicina/administración & dosificación , Ifosfamida/administración & dosificación , Sarcoma/tratamiento farmacológico , Adulto , Antibióticos Antineoplásicos/efectos adversos , Antineoplásicos Alquilantes/efectos adversos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Epirrubicina/efectos adversos , Femenino , Humanos , Ifosfamida/efectos adversos , Infusiones Intravenosas , Inyecciones Intravenosas , Italia , Riñón/efectos de los fármacos , Leucopenia/inducido químicamente , Masculino , Mesna/uso terapéutico , Persona de Mediana Edad , Sistema Nervioso Periférico/efectos de los fármacos , Sustancias Protectoras/uso terapéutico , Sarcoma/secundario , Trombocitopenia/inducido químicamente , Resultado del TratamientoRESUMEN
Operation of the thermonuclear fusion experiment ITER requires additional heating via injection of neutral beams from accelerated negative ions. In the SPIDER test facility, under construction in Padova, the production of negative ions will be studied and optimised. STRIKE (Short-Time Retractable Instrumented Kalorimeter Experiment) is a diagnostic used to characterise the SPIDER beam during short pulse operation (several seconds) to verify if the beam meets the ITER requirements about the maximum allowed beam non-uniformity (below ±10%). The major components of STRIKE are 16 1D-CFC (Carbon-Carbon Fibre Composite) tiles, observed at the rear side by a thermal camera. This contribution gives an overview of some tests under high energy particle flux, aimed at verifying the thermo-mechanical behaviour of several CFC prototype tiles. The tests were performed in the GLADIS facility at IPP (Max-Plank-Institut für Plasmaphysik), Garching. Dedicated linear and nonlinear simulations were carried out to interpret the experiments and a comparison of the experimental data with the simulation results is presented. The results of some morphological and structural studies on the material after exposure to the GLADIS beam are also given.
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A prototype system of the Langmuir probes for SPIDER (Source for the production of Ions of Deuterium Extracted from RF plasma) was manufactured and experimentally qualified. The diagnostic was operated in RF (Radio Frequency) plasmas with cesium evaporation on the BATMAN (BAvarian Test MAchine for Negative ions) test facility, which can provide plasma conditions as expected in the SPIDER source. A RF passive compensation circuit was realised to operate the Langmuir probes in RF plasmas. The sensors' holder, designed to better simulate the bias plate conditions in SPIDER, was exposed to a severe experimental campaign in BATMAN with cesium evaporation. No detrimental effect on the diagnostic due to cesium evaporation was found during the exposure to the BATMAN plasma and in particular the insulation of the electrodes was preserved. The paper presents the system prototype, the RF compensation circuit, the acquisition system (as foreseen in SPIDER), and the results obtained during the experimental campaigns.
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In the development of the neutral beam injector for ITER experiment, the test facility SPIDER is going to be built. To measure the beam parameters, several diagnostics are used. One of them is the Short-Time Retractable Instrumented Kalorimeter Experiment (STRIKE) which measures beam uniformity, beamlet divergence, and stripping losses. This contribution gives an overview of the diagnostics dedicated to these measurements: thermal cameras, thermocouples, current sensors, and electrostatic sensors. The specifications of these diagnostics have been defined according to the results of electrostatic and thermal simulations. A failure modes and effects analysis has been performed during the design. Consequently the project of the STRIKE diagnostics has been optimized to reduce the possible failure risks.
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To study and optimise negative ion production for the ITER neutral beam injectors, a test facility is under construction in Padova with the aim of testing beam characteristics and to verify the source proper operation. The instrumented calorimeter STRIKE (short-time retractable instrumented kalorimeter experiment) is being developed to characterise the SPIDER (Source for Production of Ion of Deuterium Extracted from RF plasma) beam during short operations. The paper presents an investigation of the response of STRIKE measurement systems. It results that biasing is necessary to cope with the influence of secondary electrons on current measurements; moreover, despite the discretisation of the recorded thermal patterns introduced by the pixels of thermal cameras, a sufficient spatial resolution is expected.
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A neutron diagnostic for high current deuterium beams is proposed for installation on the spectral shear interferometry for direct electric field reconstruction (SPIDER, Source for Production of Ion of Deuterium Extracted from RF plasma) test beam facility. The proposed detection system is called Close-contact Neutron Emission Surface Mapping (CNESM). The diagnostic aims at providing the map of the neutron emission on the beam dump surface by placing a detector in close contact, right behind the dump. CNESM uses gas electron multiplier detectors equipped with a cathode that also serves as neutron-proton converter foil. The cathode is made of a thin polythene film and an aluminium film; it is designed for detection of neutrons of energy >2.2 MeV with an incidence angle < 45°. CNESM was designed on the basis of simulations of the different steps from the deuteron beam interaction with the beam dump to the neutron detection in the nGEM. Neutron scattering was simulated with the MCNPX code. CNESM on SPIDER is a first step towards the application of this diagnostic technique to the MITICA beam test facility, where it will be used to resolve the horizontal profile of the beam intensity.
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The ITER heating neutral beam (HNB) injector, based on negative ions accelerated at 1 MV, will be tested and optimized in the SPIDER source and MITICA full injector prototypes, using a set of diagnostics not available on the ITER HNB. The RF source, where the H(-)∕D(-) production is enhanced by cesium evaporation, will be monitored with thermocouples, electrostatic probes, optical emission spectroscopy, cavity ring down, and laser absorption spectroscopy. The beam is analyzed by cooling water calorimetry, a short pulse instrumented calorimeter, beam emission spectroscopy, visible tomography, and neutron imaging. Design of the diagnostic systems is presented.