RF-knockout extraction system for the National Centre of Oncological Hadrontherapy synchrotron

The National Centre for Oncological Hadrontherapy CNAO was established on 2001 by the Italian Health Ministry. At present the centre is under commissioning in Pavia and will treat the first patients in one year. The CNAO is the first Italian Centre for the treatment of patients affected by tumors by means of ions beams: treatments with an active scanning of both protons and carbon ions will be possible. Protons are required to have kinetic energy of about 220 MeV, while about 4.8 GeV, i.e. 400 MeV/u, are necessary for the carbon ions beam. A synchrotron will provide such energies. The extraction of the beam from an hadrontherapy synchrotron must be very slow, because the extracted beam (called spill) must have low and constant intensity and must be long, in order to facilitate the measurement and control of the radiation dose delivered to patients. The extraction interval must be about 1 s long: as a consequence a multi-turn extraction is needed. The slow extraction is based on the third order resonance and a sextupole magnet is used to excite the resonance. The beam will be driven into the resonance by a betatron core, which accelerates the beam. The possibility of using the RF-knockout system as an alternative way to drive the beam into the resonance is also under consideration. RF-knockout method has some advantages: in particular the start and stop time of the extraction are very fast. This characteristics is useful for some special treatments needs, such as the synchronization with the breathing of the patient. The aim of this thesis is to verify the feasibility of the RF-knockout extraction method and the optimization of the corresponding performances with the already present hardware (and minimum upgrades) of CNAO synchrotron. The RF-knockout extraction system involves the use of a kicker, which perturbs the beam horizontally. The frequency of the signal given to the kicker must match the horizontal betatron frequency. The particles momentum spread determines a tune spread, due to the horizontal chromaticity. With a tune spread, the RF frequency must vary to cover all the particle tunes. Two types of signals have been studied in order to obtain a constant spill with a minimum ripple: - a carrier wave with a frequency modulation; - a noise at a given range of frequencies. A dedicated simulation program has been written in C++ language to track the particles in the synchrotron with the RF-knockout. The program performs a six-dimensional tracking. Any number of particles can be tracked for any number of turns in the synchrotron. The RF signal can be defined by the user. The synchrotron lattice and the initial particle coordinates are the input of the program. The frequency modulated signal is commonly used in other hadrontherapy synchrotrons, as the ones in Japan. With that method the extracted beam has a ripple at the frequency of the modulating signal. The noise signal does not produce an extracted beam with ripple, so it is preferable. The intensity of the extracted beam decays exponentially with time and the characteristic time depends on the kick amplitude. The amplitude of the kick must be increased to have a constant spill. An amplitude modulation function has been found to have a constant spill in the first 70% of the extraction. The simulation has shown that, in the most demanding conditions, i.e. with a carbon ion beam at maximum energy and minimum emittance, a relatively fast extraction (1 s) can be obtained with a perturbation of less than 10^-6 rad. To have a slower extraction, an extraction of the proton beam or an extraction of the carbon ion beam at less energy, the perturbation should be smaller

Touschek lifetime studies and optimization of the ESRF: present and upgraded lattice

The lifetime of the electron beam in a storage ring is a measure of how fast the electrons are being lost. This is an important parameter in third generation synchrotron light sources for a number of reasons. First of all, the intensity of radiation seen in an experiment, at the end of a beamline, is proportional to the electron beam current. Further, as the current changes, there are important effects on the x-ray optics along the beamline. Changes in heat-load can effect the transport and focusing properties of the beamline. For these reasons, more electrons must be injected when the current drops below some threshold value. The electron beam lifetime determines the injection frequency. If the lifetime is long enough, the injections can be done less frequently. The injection disturbs the stability of the stored beam, it increases the radiation losses and it increases the energy consumption of the facility, because the linac and the synchrotron booster must be turned on during the injection. When the lifetime is too short, the top-up injection is needed. The top-up injection is a very frequent injection of electrons into the storage ring, one every few minutes, and it is done without interrupting the x-ray flux and the users’ experiments. Top-up injection needs a high injection efficiency. In the ESRF storage ring, the top-up injection is not used now. In the low emittance ESRF upgrade storage ring, the top-up injection will be used, because the very low horizontal emittance, from the actual εx = 4 nm to εx = 150 pm, will result in a very short Touschek lifetime. The Touschek effect is the main limitation in the beam lifetime in third generation synchrotron light sources. It is a single scattering between two electrons of the bunch. The collision can transfer momentum from transverse to longitudinal motion and both the electrons can exceed the momentum acceptance, in which case they are lost. The Touschek scattering probability is larger when the charge density is high, so when emittances and β functions are small and the current is high. The Touschek effect depends on many electron beam and machine parameters: the RF voltage, the bunch current, the bunch length, the beam emittances and the momentum acceptance. The small horizontal emittance storage rings, necessary to have a high brilliance x-ray source, have small β-functions and horizontal dispersion and strong focusing magnets. The natural chromaticity of low emittance rings is very high and strong sextupole magnets are needed to correct it. High nonlinear fields from sextupoles cause a high amplitude-dependent tune variation. The large tune shift with amplitude causes many resonance crossings for off-axis particles and therefore a small dynamic aperture. The small dynamic aperture causes a small injection efficiency. The positive chromaticity, needed for the bunch stability, and the strong nonlinear fields give large tunes variation with momentum. This can cause the strong resonance crossing of off-momentum particles and therefore a small momentum acceptance. The small momentum acceptance causes a short Touschek lifetime. Momentum acceptance is determined by RF voltage and longitudinal dynamic acceptance, which depends on the sextupole setting. A model able to predict the Touschek lifetime, given the lattice, the current, the emittances, the RF voltage, the size of the vacuum chamber, is useful to optimize the parameters of the present ESRF lattice and the new low emittance ESRF upgrade lattice. In this thesis, a model able to predict lifetime of the beam has been developed and tested with measurements and it has been used to optimize parameters and sextupole settings. The model is also used for the new lattice lifetime studies. In chapter 1, a brief description of the ESRF facility and on its upgrade program is given. In chapter 2, the Touschek lifetime derivation, from the Møller scattering differential cross section, is presented. The effects of the spin polarization in the Touschek lifetime are also treated. In chapter 3, the measurements of some parameters, relevant for the Touschek lifetime, done for the ESRF storage ring, are reported. The RF voltage calibration factor between the readout value and the real voltage applied to the cavity is measured from the synchrotron tune and the synchronous phase measurements. A bunch lengthening with current model, derived from measurements, is presented. The momentum acceptance computation, using a 6-D particle tracking code, is described. In chapter 4, the lifetime measurements are described: the vacuum lifetime, that must be measured before all the Touschek lifetime measurements; the effect of the spin polarization on the Touschek lifetime and the spin polarization time; the Touschek lifetime versus the RF voltage; the Touschek lifetime versus the horizontal scraper position. In chapter 5, the optimization of the sextupole setting is described: the multiobjective generic algorithm used is described, the results of the optimization and the measurements are reported. In chapters 6 and 7, the Touschek lifetime model, described in previous chapters, is used to study the Touschek lifetime of the low emittance ESRF upgrade lattice. The bunch length model and the emittance growth due to the intrabeam scattering are used to predict the Touschek lifetime of the new lattice for different modes. In first appendix, an overview of the beam physics in an electron storage ring is given. In the first section, the single particle dynamics without synchrotron radiation is treated. In the second section, the effects of synchrotron radiation on the single particle dynamics are reported. In the third section two current dependent effects, related to the beam lifetime, are treated: the bunch lengthening effect due to the longitudinal wakefield and the intrabeam scattering. In second appendix, a matlab code, developed during the thesis work and used to simulate the spin depolarization with a kicker, is described. In third appendix, two possible momentum compaction factor measurements are presented. In fourth appendix, the effect of synchrotron motion on the dynamic aperture computation is described

NEUROBEHAVIORAL FUNCTIONS, SERUM PROLACTIN AND PLASMA RENIN ACTIVITY OF MANGANESE-EXPOSED WORKERS

Objective of this study was to assess effects of manganese (Mn) exposure on 56 workers employed in a Mn welding workshop of a machine building factory in Taiyuan (Shanxi Province, P.R. China) for a mean period of 16.1 years. The mean air Mn level in the workshop was 138.4 μg/m3. Neurobehavioral Core Test Battery (NCTB), including the Profile of Mood States (POMS), was performed. Blood pressure (BP) increase following immediate stand-up (BP-IS), serum prolactin (PRL) and plasma renin activity (PRA) in supine position were also determined. Most of the NCTB scores of the Mn-exposed workers were lower than those of the controls, while the POMS scores were higher, indicating a Mn-induced impairment of neurophysiological functions and a deflection of mood towards negative emotion states. PRL values of the Mn-exposed workers were higher than those of the controls. BP-IS of Mn-exposed workers was significantly lower than that of the controls. PRA of the same workers was augmented more than 200 %. In the Mn-exposed workers, the higher PRL values are possibly due to a reduced inhibitory effect on pituitary lactotrope cells by the tubero-infundibular dopamine system; the decreased BP-IS was referred to imbalance between the sympathetic and parasympathetic activities, whereas the higher basal PRA was thought to depend on neuroendocrine changes (including increased central sympathetic tone) and/or on a direct effect of Mn on renal juxta-glomerular cells. On the whole, this study demonstrates that occupational Mn exposure is responsible for neurobehavioral changes coexisting with alterations of neuroendocrine and humoral systems

Prognostic significance of pathologic lymph node invasion in metastatic renal cell carcinoma in the immunotherapy era

Background This study aimed to test the prognostic significance of pathologically confirmed lymph node invasion in metastatic renal cell carcinoma (mRCC) patients in this immunotherapy era. Methods Surgically treated mRCC patients were identified in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2018. Kaplan-Meier plots and multivariable Cox-regression models were fitted to test for differences in cancer-specific mortality (CSM) and overall mortality (OM) according to N stage (pN0 vs pN1 vs. pNx). Subgroup analyses addressing pN1 patients tested for CSM and OM differences according to postoperative systemic therapy status. Results Overall, 3149 surgically treated mRCC patients were identified. Of these patients, 443 (14%) were labeled as pN1, 812 (26%) as pN0, and 1894 (60%) as pNx. In Kaplan-Meier analyses, the median CSM-free survival was 15 months for pN1 versus 40 months for pN0 versus 35 months for pNx (P < 0.001). In multivariable Cox regression analyses, pN1 independently predicted higher CSM (hazard ratio [HR], 1.88; P < 0.01) and OM (HR, 1.95; P < 0.01) relative to pN0. In sensitivity analyses addressing pN1 patients, postoperative systemic therapy use independently predicted lower CSM (HR, 0.73; P < 0.01) and OM (HR, 0.71; P < 0.01). Conclusion Pathologically confirmed lymph node invasion independently predicted higher CSM and OM for surgically treated mRCC patients. For pN1 mRCC patients, use of postoperative systemic therapy was associated with lower CSM and OM. Consequently, N stage should be considered for individual patient counseling and clinical decision-making

Regional differences in clear cell metastatic renal cell carcinoma patients across the USA

Purpose To test for regional differences in clear cell metastatic renal cell carcinoma (ccmRCC) patients across the USA. Methods The Surveillance, Epidemiology, and End Results (SEER) database (2000–2018) was used to tabulate patient (age at diagnosis, sex, race/ethnicity), tumor (N stage, sites of metastasis) and treatment characteristics (proportions of nephrectomy and systemic therapy), according to 12 SEER registries. Multinomial regression models, as well as multivariable Cox regression models, tested the overall mortality (OM) adjusting for those patient, tumor and treatment characteristics. Results In 9882 ccmRCC patients, registry-specific patient counts ranged from 4025 (41%) to 189 (2%). Differences across registries existed for sex (24–36% female), race/ethnicity (1–75% non-Caucasian), N stage (N1 25–35%, NX 3–13%), proportions of nephrectomy (44–63%) and systemic therapy (41–56%). Significant inter-registry differences remained after adjustment for proportions of nephrectomy (46–63%) and systemic therapy (35–56%). Unadjusted 5-year OM ranged from 73 to 85%. In multivariable analyses, three registries exhibited significantly higher OM (SEER registry 5: hazard ratio (HR) 1.20, p = 0.0001; SEER registry 7:HR 1.15, p = 0.008M SEER registry 10: HR 1.15, p = 0.04), relative to the largest reference registry (n = 4025). Conclusion Important regional differences including patient, tumor and treatment characteristics exist, when ccmRCC patients included in the SEER database are studied. Even after adjustment for these characteristics, important OM differences persisted, which may require more detailed analyses to further investigate these unexpected differences

Could synchrotron light sources benefit from the experience at CERN with beams split in horizontal phase space?

International audienceThis article reviews the recent activities carried out at CERN in terms of transverse beam splitting with proton beams. Thanks to intense experimental and theoretical activities, the recently-proposed approach of splitting beams in the horizontal phase space using stable islands moved out of the test stage and it became a mature technique of beam manipulation to perform multi-turn extraction. It is therefore timely to address the question whether stable islands can be applied to other branches of accelerator physics, in view of bringing new means of improving ring’s performance. This is the case of synchrotron light machines, where the use of stable islands could lead to new developments, and in this paper options are presented and discussed

Could synchrotron light sources benefit from the experience at CERN with beams split in horizontal phase space?

This article reviews the recent activities carried out at CERN in terms of transverse beam splitting with proton beams. Thanks to intense experimental and theoretical activities, the recently-proposed approach of splitting beams in the horizontal phase space using stable islands moved out of the test stage and it became a mature technique of beam manipulation to perform multi-turn extraction. It is therefore timely to address the question whether stable islands can be applied to other branches of accelerator physics, in view of bringing new means of improving ring’s performance. This is the case of synchrotron light machines, where the use of stable islands could lead to new developments, and in this paper options are presented and discussed