Preliminary results of BETSI test bench upgrade at CEA-Saclay.

The Banc d'Etude et de Tests des Sources d'Ions (BETSI) test bench was built in 2009 for the Spiral2 project. Year after year, upgrades were done on the low energy beam line in order to have a complete injector equipped with 2 solenoids and vacuum chambers with multiple viewports for various kinds of beam-diagnostics. BETSI was designed for a 50 kV high voltage, and all the sources that were installed on the platform were also designed for that voltage. As the advanced light ion source extraction system ions source family is getting larger, the design is made for higher extraction voltages. As the common extraction voltage is 100 kV, the BETSI platform was upgraded to this voltage value. The control-command was upgraded, and at this voltage, a great care on the electromagnetic protections was taken in order to protect the equipment when spark occurs. This paper describes the choice of the upgrade, its installation, and some performances already obtained with a permanent magnet ion source equipped with a large accelerating tube.

Commissioning of the ECR ion source of the high intensity proton injector of the Facility for Antiproton and Ion Research (FAIR).

The CEA at Saclay is in charge of developing and building the ion source and the low energy line of the proton linac of the FAIR (Facility for Antiproton and Ion Research) accelerator complex located at GSI (Darmstadt) in Germany. The FAIR facility will deliver stable and rare isotope beams covering a huge range of intensities and beam energies for experiments in the fields of atomic physics, plasma physics, nuclear physics, hadron physics, nuclear matter physics, material physics, and biophysics. A significant part of the experimental program at FAIR is dedicated to antiproton physics that requires an ultimate number 7 × 1010 cooled pbar/h. The high-intensity proton beam that is necessary for antiproton production will be delivered by a dedicated 75 mA/70 MeV proton linac. A 2.45 GHz microwave ion source will deliver a 100 mA H+ beam pulsed at 4 Hz with an energy of 95 keV. A 2 solenoids low energy beam transport line allows the injection of the proton beam into the radio frequency quadrupole (RFQ) within an acceptance of 0.3π mm mrad (norm. rms). An electrostatic chopper system located between the second solenoid and the RFQ is used to cut the beam macro-pulse from the source to inject 36 µs long beam pulses into the RFQ. At present time, a Ladder-RFQ is under construction at the University of Frankfurt. This article reports the first beam measurements obtained since mid of 2016. Proton beams have been extracted from the ECR ion source and analyzed just after the extraction column on a dedicated diagnostic chamber. Emittance measurements as well as extracted current and species proportion analysis have been performed in different configurations of ion source parameters, such as magnetic field profile, radio frequency power, gas injection, and puller electrode voltage.

Possible patterns of epidermal melanocyte disappearance in nonsegmental vitiligo: a clinicopathological study.

BACKGROUND: The depigmentation of vitiligo results in a progressive and chronic melanocyte loss with rare melanocytes occasionally remaining in the epidermis or the hair follicle reservoirs. Destruction by immune infiltrates in close contact with melanocytes within microvesicles and/or detachment of melanocytes followed by their transepidermal elimination should be regarded as possible mechanisms of chronic loss of pigment cells. OBJECTIVES: To assess the frequency of these two histological findings and to establish a direct correlation with clinical features. METHODS: This was a prospective observational study that took place over 1 year. Each patient received a standardized evaluation that included daylight and Wood's lamp examinations, pictures, biopsies performed on the marginal area, and histological and immunohistological studies. A second examination to assess the activity of the lesions was performed 1 year after inclusion in the study. Clinical changes associated with microvesicles were compared with those associated with detached melanocytes from the basal layer. RESULTS: This study included 50 patients. The histological findings were classified as inflammatory with isolated microvesicles (29 cases), noninflammatory with only detached melanocytes from the basal layer (12 cases) and a combination of coexisting microvesicles and detached melanocytes (six cases). Correlations were obtained between the histological findings and clinical features (aspect and activity of the lesions) and E-cadherin expression. CONCLUSIONS: Our data suggest the existence of two patterns of melanocyte disappearance in nonsegmental vitiligo.

Hypochromic vitiligo: delineation of a new entity.

BACKGROUND: Hypochromic vitiligo is a rare entity that has been reported only twice under the term 'vitiligo minor', with an absence of clear delineation. OBJECTIVES: To delineate hypochromic vitiligo through a case series of patients with typical bilateral hypopigmented lesions affecting the face and trunk. METHODS: This is a retrospective multicentric evaluation study conducted in eight departments of dermatology in France, Belgium, Senegal and Saudi Arabia. RESULTS: Twenty-four cases of hypochromic vitiligo were identified. Fourteen were men and 10 women. The mean age at diagnosis was 35·4 years (range 8-66). Strikingly, all patients were dark skinned, with skin types V and VI. The pattern of distribution was highly similar in most of the patients (18 of 24), with involvement of the face and neck area predominating on seborrhoeic areas associated with multiple isolated hypopigmented macules involving predominantly the scalp. The retrospective nature of this study is its main limitation. CONCLUSIONS: Hypochromic vitiligo is not yet part of a conventional classification. The disease seems to be limited to individuals with dark skin types. Hypopigmented seborrhoeic face and neck involvement associated with hypopigmented macules of the trunk and scalp is the hallmark of the disease.

Possible mechanisms by which topical 5-Fluorouracil and dermabrasion could induce pigment spread in vitiligo skin: an experimental study.

The combination of skin ablation and 5-Fluorouracil (5-FU) ointment was previously tried in the treatment of vitiligo, and good results were specifically reported in glabrous skin without follicular melanocyte reservoirs. Methods. This study was carried out on the skins of seven guinea pigs: three were treated with mechanical dermabrasion plus topical 5-FU in an achromic area contiguous to a pigmented area; two were treated by only dermabrasion in a similar area; and two were treated by topical 5-FU alone. Clinical, histological, and ultrastructural studies were performed over two months. Results. In guinea pigs treated with dermabrasion plus 5-FU, we observed firstly a delay of wound healing with an obvious inflammatory reaction, and, after two months, evident pigment spread from the pigmented into the achromic area. After six months, we noticed black hair regrowing in the achromic area. Pigment spread was not seen in the guinea pigs skin treated by either dermabrasion or topical 5-FU. We suggest that the inflammatory mediators and enzymes (metalloproteinases), which are locally released over a long time, could stimulate and facilitate melanocyte proliferation and migration through the enlarged intercellular spaces of the epidermis. This sequence of events may be applied to vitiligo patients treated with 5-FU on ablated lesions.

Clinical features and histological findings are potential indicators of activity in lesions of common vitiligo.

BACKGROUND: Unstable vitiligo lesions are usually considered to be contraindications for surgical treatment. Unfortunately, in the majority of common vitiligo cases, neither accurate clinical signs nor routine blood tests are available to determine whether or not the disease is active. OBJECTIVES: To establish a direct correlation between the clinical aspect of vitiligo lesions and their activity. METHODS: This was a prospective observational study that took place over 1 year. For each patient, a standardized evaluation included both a careful daylight and Wood's lamp examination, pictures, biopsies performed at the marginal area and histological and immunohistological studies. A second examination to assess the activity of the lesions correctly was performed 1 year after inclusion in the study. Both the clinical changes and the histological features of the lesions in actively spreading vitiligo were compared with those in stable vitiligo. RESULTS: This study included 50 patients. The lesions were classified as hypomelanotic with poorly defined borders (HPDB, 29 cases) or amelanotic with sharply demarcated borders (ASDB, 21 cases). One year after the biopsy, of the 48 patients still in the study, 20 had lesions that were considered to be stable and 28 had active lesions. Correlations were successfully obtained between clinical aspects, histological findings and vitiligo activity. The HPDB and ASDB lesions were correlated respectively with active and stable status (P < 0·001). CONCLUSIONS: A simple clinical examination including a Wood's lamp examination may allow reliable and efficient evaluation of the stability of vitiligo lesions.

Guidelines for the management of vitiligo: the European Dermatology Forum consensus.

The aetiopathogenic mechanisms of vitiligo are still poorly understood, and this has held back progress in diagnosis and treatment. Up until now, treatment guidelines have existed at national levels, but no common European viewpoint has emerged. This guideline for the treatment of segmental and nonsegmental vitiligo has been developed by the members of the Vitiligo European Task Force and other colleagues. It summarizes evidence-based and expert-based recommendations (S1 level).

DISCRIMINATION OF Burkholderia mallei/pseudomallei FROM Burkholderia thailandensis BY SEQUENCE COMPARISON OF A FRAGMENT OF THE RIBOSOMAL PROTEIN S21 (RPSU) GENE.

Discrimination of Burkholderia (B.) pseudomallei and B. mallei from environmental B. thailandensis is challenging. We describe a discrimination method based on sequence comparison of the ribosomal protein S21 (rpsU) gene.The rpsU gene was sequenced in ten B. pseudomallei, six B. mallei, one B. thailandensis reference strains, six isolates of B. pseudomallei, and 37 of B. thailandensis. Further rpsU sequences of six B. pseudomallei, three B. mallei, and one B. thailandensis were identified via NCBI GenBank. Three to four variable base-positions were identified within a 120-base-pair fragment, allowing discrimination of the B. pseudomallei/mallei-cluster from B. thailandensis, whose sequences clustered identically. All B. mallei and three B. pseudomallei sequences were identical, while 17/22 B. pseudomallei strains differed in one nucleotide (78A>C). Sequences of the rpsU fragment of 'out-stander' reference strains of B. cepacia, B. gladioli, B. plantarii, and B. vietnamensis clustered differently.Sequence comparison of the described rpsU gene fragment can be used as a supplementary diagnostic procedure for the discrimination of B. mallei/pseudomallei from B. thailandensis as well as from other species of the genus Burkholderia, keeping in mind that it does not allow for a differentiation between B. mallei and B. pseudomallei.

Revised classification/nomenclature of vitiligo and related issues: the Vitiligo Global Issues Consensus Conference.

During the 2011 International Pigment Cell Conference (IPCC), the Vitiligo European Taskforce (VETF) convened a consensus conference on issues of global importance for vitiligo clinical research. As suggested by an international panel of experts, the conference focused on four topics: classification and nomenclature; definition of stable disease; definition of Koebner's phenomenon (KP); and 'autoimmune vitiligo'. These topics were discussed in seven working groups representing different geographical regions. A consensus emerged that segmental vitiligo be classified separately from all other forms of vitiligo and that the term 'vitiligo' be used as an umbrella term for all non-segmental forms of vitiligo, including 'mixed vitiligo' in which segmental and non-segmental vitiligo are combined and which is considered a subgroup of vitiligo. Further, the conference recommends that disease stability be best assessed based on the stability of individual lesions rather than the overall stability of the disease as the latter is difficult to define precisely and reliably. The conference also endorsed the classification of KP for vitiligo as proposed by the VETF (history based, clinical observation based, or experimentally induced). Lastly, the conference agreed that 'autoimmune vitiligo' should not be used as a separate classification as published evidence indicates that the pathophysiology of all forms of vitiligo likely involves autoimmune or inflammatory mechanisms.

Light ion source for proton∕deuteron production at CEA Saclay for the Spiral2 project.

The production of rare radioactive ion beam (RIB) far from the valley of stability is one of the final purposes of the Spiral2 facility in Caen. The RIB will be produced by impinging a deuteron beam onto a carbon sample to produce a high neutron flux, which will interact with a uranium target. The primary deuteron beam is produced by an ion source based on ECR plasma generation. The deuteron source and the low energy beam transport (LEBT) has been assembled and tested at CEA Saclay. Diagnostics from other laboratories were implemented on the LEBT in order to characterize the deuteron beam produced and compare it to the initial simulations. The ion source has been based on a SILHI-type source, which has demonstrated good performances in pulsed and continuous mode, and also a very good reliability on long term operation. The 5 mA of deuteron beam required at the RFQ entrance is extracted from the plasma source at the energy of 40 kV. After a brief description of the experimental set-up, this article reports on the first beam characterization experiments.

Preliminary results of the International Fusion Materials Irradiation Facility deuteron injector.

In the framework of the IFMIF-EVEDA project (International Fusion Materials Irradiation Facility-Engineering Validation and Engineering Design Activities), CEA∕IRFU is in charge of the design, construction, and characterization of the 140 mA continuous deuteron injector, including the source and the low energy beam line. The electron cyclotron resonance ion source which operates at 2.45 GHz is associated with a 4-electrode extraction system in order to minimize beam divergence at the source exit. Krypton gas injection is foreseen in the 2-solenoid low energy beam line. Such Kr injection will allow reaching a high level of space charge compensation in order to improve the beam matching at the radio frequency quadrupole (RFQ) entrance. The injector construction is now completed on the Saclay site and the first plasma and beam production has been produced in May 2011. This installation will be tested with proton and deuteron beams either in pulsed or continuous mode at Saclay before shipping to Japan. In this paper, after a brief description of the installation, the preliminary results obtained with hydrogen gas injection into the plasma chamber will be reported.

Halo naevi and leukotrichia are strong predictors of the passage to mixed vitiligo in a subgroup of segmental vitiligo.

BACKGROUND: Until now, segmental vitiligo has been considered as a stable entity and mixed vitiligo, the association of segmental and nonsegmental vitiligo, has been reported rarely. OBJECTIVES: The aim of this study was to search for factors associated with the generalization of vitiligo in patients with segmental vitiligo. PATIENTS AND METHODS: This was a prospective observational study conducted in the vitiligo clinic of the Department of Dermatology of Bordeaux, France. The Vitiligo European Task Force questionnaire was completed for each patient attending the clinic with a confirmed diagnosis of segmental vitiligo after exclusion of other forms of vitiligo (focal, mucosal, not classifiable.) Thyroid function and antithyroid antibodies were screened if not obtained in the previous year. RESULTS: One hundred and twenty-seven patients were recruited: 101 had segmental vitiligo and 26 had segmental vitiligo that evolved into mixed vitiligo; 56 were male and 71 were female. Most patients had onset of segmental vitiligo before the age of 18. When conducting multivariate analysis, we found the following to be independent factors associated with the evolution of patients' disease from segmental vitiligo to mixed vitiligo: initial percentage of body surface involvement of the segment >1% [odds ratio (OR) 15·14, P=0·002], the presence of halo naevi (OR 24·82, P=0·0001) and leukotrichia (OR 25·73, P=0·0009). CONCLUSIONS: Halo naevi association and leukotrichia at first consultation in segmental vitiligo are risk factors for the progression of segmental vitiligo to mixed vitiligo. In addition, this progression of segmental vitiligo to mixed vitiligo carries a stronger link if initial segmental involvement is situated on the trunk.

Multivariate analysis of factors associated with early-onset segmental and nonsegmental vitiligo: a prospective observational study of 213 patients.

BACKGROUND: Although mixed forms have been described recently, segmental (SV) and nonsegmental vitiligo (NSV) are considered as clinically distinct. However, limited epidemiological data are available to help distinguish associated factors, and recent genome-wide association studies have been restricted to NSV. The higher prevalence of SV in children is helpful when comparing the two major presentations of the disease. OBJECTIVE: To compare factors associated with SV and NSV, especially for markers of autoimmunity or autoinflammation. METHODS: We conducted a single-centre prospective observational study in patients aged 17 years or under with a confirmed diagnosis of SV or NSV at the vitiligo clinic between 1 January 2006 and 1 July 2010. The Vitiligo European Task Force questionnaire was completed for each patient, and thyroid function and antithyroid antibodies were screened if not obtained in the previous year. Other forms of vitiligo (focal, mucosal, not classifiable) were excluded. RESULTS: A total of 213 children were included, 142 with NSV, 59 with SV and 12 with mixed vitiligo. There was no significant statistical difference for sex or age at onset between patients with SV and NSV. Halo naevi were significantly more frequent in NSV than in SV [odds ratio (OR) 7·58, P < 0·01). Patients with NSV more frequently had a positive family history of vitiligo (OR 2·25, P=0·02) and a marked familial autoimmunity background (OR 2·22, P = 0·01). CONCLUSIONS: Our study clearly shows that features of inflammation (pruritus)/autoimmunity (halo naevi, thyroid antibodies) are strongly linked to NSV, together with a familial background of vitiligo and autoimmunity.

Different phenotypes of segmental vitiligo based on a clinical observational study.

BACKGROUND: Segmental vitiligo and generalized vitiligo are in general considered separate entities. However, clinico-epidemiological data on segmental vitiligo are scarce compared with those of generalized vitiligo. OBJECTIVE: To analyse the clinical profile and distribution pattern of lesions in segmental vitiligo patients. METHODS: Segmental vitiligo patients were examined and questioned in a prospective and retrospective setting. The distribution and extent of the lesions were evaluated using clinical photographs. RESULTS: Different phenotypes of segmental vitiligo were found, including the unilateral segmental type (124 patients; group 1), the bilateral segmental type (three patients; group 2) and the mixed segmental and generalized type (14 patients; group 3). Furthermore, lesions were present with (10%) or without associated halo naevi. The age of onset of segmental vitiligo (median 14years) was significantly different between the three subgroups (P=0.028). Extensive involvement of segmental vitiligo lesions on trunk and extremities was significantly (P=0.031) more observed in patients with a lower age of onset, while the generalized vitiligo lesions in the mixed vitiligo group were mostly very mild. Associated autoimmune diseases were reported in 11%, whereas a positive family history for vitiligo was present in 14.9% of patients. Lesions were not strictly dermatomal nor Blaschkolinear, although a typical recurring pattern could be observed. CONCLUSION: Our data provide clinical evidence that segmental vitiligo and generalized vitiligo are parts of the same disease spectrum and that segmental vitiligo could have a polygenetic background as well. Whether different aetiopathological mechanisms underlie the different clinical phenotypes of segmental vitiligo remain to be elucidated.

A 140 mA cw deuteron electron cyclotron resonance source for the IFMIF-EVEDA project.

In the framework of the IFMIF-EVEDA phase (International Fusion Materials Irradiation Facility-Engineering Validation and Engineering Design Activities), the CEA-Saclay is in charged of the design and realization of the 140 mA cw deuteron source. The IFMIF EVEDA demonstrator will be installed in Japan in the next six years and will have to accelerate the deuteron beam up to 9 MeV. CEA will build the source and the low energy beam line (LEBT) and will test the cw high intensity deuteron production at Saclay. The SILHI source is an electron cyclotron resonance (ECR) source, operating at 2.45 GHz. In 2001, it produced more than 130 mA of deuteron beam in pulsed mode to minimize neutron production. Such a result pushes to develop a new ECR source based on the SILHI design and equipped with a specific extraction system. Several options of the accelerator column will be implemented in order to improve the reliability and the efficiency of the source. The IFMIF source and LEBT design will be reported.

BETSI, a new test bench for ion sources optimization at CEA SACLAY.

In the framework of several International HPPA projects (such as IFMIF, IPHI, and Spiral2) the CEA handles the design and the developments of several electron cyclotron resonance (ECR) ion sources. For the IFMIF EVEDA demonstrator, a 140 mA cw extracted deuteron beam will be required for high yield of neutron production. For radioactive ion production in the Spiral2 project, several milliamperes of deuterons will be delivered with a permanent magnet source. The optimization of the beam quality at the entrance of the radio frequency quadropole (RFQ) accelerator system triggered the need of a new test bench for ion source optimization and beam qualification. The BETSI ion source test bench will operate up to 50 kV and ignite cw or pulsed hydrogen plasma with a 2.45 GHz magnetron. Great care has already been taken to design electrostatic optics of the extraction system to minimize the emittance growth. Plasma diagnostics will be inserted in the source chamber and several beam diagnostics (emittance and current measurements, beam species analysis) will also be implemented on the low energy beam line transport (LEBT). These diagnostics allow the simultaneous analysis of the beam quality with the plasma parameters of the source. Regional funding request will also be needed to improve the LEBT for space charge compensation measurements. The design of the present and upgraded test bench will be reported as well as the first extracted beam analysis.

The melanocytorrhagic hypothesis of vitiligo tested on pigmented, stressed, reconstructed epidermis.

Common generalized vitiligo is an acquired depigmenting disorder characterized by a chronic and progressive loss of melanocytes from the epidermis and hair follicles. We previously proposed a new theory that vitiligo involves the chronic detachment and transepidermal loss of melanocytes caused by autoimmune, neural and impaired redox mechanisms associated with mechanical trauma. In this study, we reconstructed epidermis on dead de-epidermized dermis with normal and/or non-segmental non-lesional vitiligo (NSV) cells and tested catecholamines or sera or hydrogen peroxide. Under unstressed conditions, the number of melanocytes located in the basal layer was significantly lower in reconstructs made with melanocytes from non-lesional NSV skin and normal keratinocytes compared with controls made with autologous normal melanocytes. The number of non-lesional NSV melanocytes was even lower in reconstructs made with keratinocytes from non-lesional NSV skin. Epinephrine and H(2)O(2) could trigger the transepidermal loss of normal and vitiligo melanocytes. Some sera induced melanocyte detachment but without any clear correlation with disease activity in the donors. In conclusion, our results are the first step to obtaining a reproducible melanocytorrhagic model in vitro with some of the stressors investigated. They support the hypothesis that NSV melanocytes have an intrinsic defect, which limits their adhesion in a reconstructed epidermis, with an enhancer effect of the vitiligo keratinocyte milieu.