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Resume Introduction Les mycobacteries atypiques (MA) sont responsables d’adenites cervico-faciales, dont l’incidence semble en augmentation. L’objectif est d’en decrire les caracteristiques cliniques, microbiologiques et therapeutiques. Materiel et methodes Etude retrospective monocentrique recensant les cas entre janvier 2008 et decembre 2017 au CHU de Nantes, France. Les criteres d’inclusion etaient : âge Resultats De 2008 a 2017, 49 patients ont ete inclus, d’âge median 28 mois (6–141 mois). Le delai median de confirmation diagnostique etait de 2,1 mois (0,7–6 mois). Les localisations etaient sous mandibulaires dans 45 % des cas, cervicales et parotidiennes dans 33 et 16 % des cas. Les principaux signes cliniques etaient un nodule ferme (70 %), violace (59 %), non douloureux (83 %), sans fievre (88 %). Les especes identifiees etaient : Mycobacterium avium (n = 26), M. lentiflavum (n = 13), M. intracellulare (n = 7), M. malmoense (n = 2), M. scrofulaceum (n = 1). Une antibiotherapie etait prescrite dans 77 % des cas. Discussion Il s’agit de la deuxieme plus grande cohorte francaise d’adenites a MA de l’enfant, confirmee microbiologiquement. La presentation la plus frequente etait un nodule sous mandibulaire ferme, violace et indolore. L’emergence de M. lentiflavum observee dans notre etude n’est pas retrouvee dans les grandes series europeennes avant 2014 mais apparait dans les series plus recentes. L’influence de l’arret de la vaccination par le BCG sur l’incidence des adenites a mycobacteries atypiques, n’est pas demontrable dans notre etude en raison du manque de donnees avant 2007. Conclusion L’adenite a MA est un diagnostic a ne pas meconnaitre chez le jeune enfant devant une tumefaction cervico-faciale violacee indolore.

Nontuberculous mycobacteria (NTM) is a common cause of lymphadenitis. A rise in incidence has been reported. Our main aim was to describe the clinical features, microbiological aspects and treatment of the disease.We conducted a retrospective, monocentric study between January 2008 and December 2017 (University Hospital of Nantes).age18 years, 1 positive lymph node specimen with identification of the species in culture, head-and-neck localization.Forty-nine patients were enrolled from 2008 to 2017. Median age was 28 months (range: 6-141 months). Median time to confirmation of diagnosis was 2.1 months (range: 0.7-6 months). The sites encountered were mandibular (45%), cervical (33%), and parotid (16%). The main clinical signs were a tender nodule (70%), purplish nodule (59%) or painless nodule (83%), without fever (88%). The species identified were: Mycobacterium avium (n=26), M. lentiflavum (n=13), M. intracellulare (n=7), M. malmoense (n=2) and M. scrofulaceum (n=1). Antibiotic treatment was frequent (77% of cases).This study is the second largest French cohort of NTM lymphadenitis in children with microbiological confirmation. The most frequent presentation was a tender, purplish, and painless mandibular nodule. The predominant species was M. avium. M. lentiflavum, which emerged during our study, does not figure in any European studies before 2014 but appears in the most recent studies. The effects of discontinuation of mandatory BCG immunization in France in NMT is not statistically demonstrable here due to lack of relevant data prior to 2007.A possible diagnosis of NTM lymphadenitis should not be overlooked in children presenting painless, purplish, cervicofacial tumefaction.

During 2016, one-quarter of the LHC main dipoles have has been powered above the 7.7 T operational field, to reach a field of 8.1 T. These tests were done to confirm the extrapolation of the training behavior based on a Gaussian tail of the quench distribution. In this paper, it is shown that a modified Gaussian distribution can be used to better model the quench distributions. We then present the data above 6.5 TeV, showing that they are compatible with the previous expectations. We present the data of retraining of sector 12, which was warmed up in 2016 to replace a magnet, and training of individual magnets that went through several thermal cycles: there is an indication that training campaigns during successive warm-ups and cool-downs could become shorter. We finally show that a significant correlation is found between the training of the installed magnet and individual test after a thermal cycle (second cool-down). On the other hand, no correlation is found with individual test under virgin conditions (first cool-down).

Anti-programmed death 1 (PD-1) antibodies are revolutionizing the treatment of many cancers, including melanoma 1. Cutaneous adverse events (AE) of anti-PD-1 antibodies are common (20%) and mainly non-specific. Bullous pemphigoids (BP) are very rare immune-related AEs induced by anti-PD-1 antibodies, with only 12 cases previously published. We report here three new cases of BP during anti PD-1 therapy with nivolumab. This article is protected by copyright. All rights reserved.

Introduction Grâce aux progres therapeutiques recents, le pronostic du melanome metastatique s’est transforme. L’immunotherapie est l’un des piliers de cette revolution. Malheureusement, nous nous heurtons a un phenomene d’immunotolerance induit en partie par les cellules tumorales aboutissant a des lymphocytes T areactifs. IDO est un mecanisme responsable identifie. En associant un anti-IDO au transfert adoptif de TILs, nous pourrions potentialiser leur activite cytotoxique vis-a-vis de la tumeur. Materiel et methodes Quatre lignees tumorales BRAF V600E+ et trois lignees sauvages pour lesquelles nous disposions de TILs autologues ont ete utilisees, stimulees ou non par l’IFN-g. L’anti-IDO etait ensuite ajoute a la concentration de 500 μM ou 1 mM. La reactivite des TILs etait evaluee par la production intracytoplasmique d’IFN-g. L’expression de molecules impliquees dans la reponse lymphocytaire a ete etudiee (CMH-I, CMH-II, PD-L1). La production d’IL-6, CXCL9 et CXCL10 a ete mesuree dans le surnageant de culture comme l’activite d’IDO (calcul du ratio kynurenine/tryptophane). Resultats A l’etat basal, IDO etait presente chez 5 lignees. Le CMH-I etait exprime par toutes les lignees et le CMH-II par seulement 4 lignees. L’anti-IDO entrainait une diminution de l’activite d’IDO et une augmentation de l’expression du CMH-I et -II de facon dose-dependante. Nous n’avons pas observe d’effet sur la reactivite des TILs. A l’etat inflammatoire, reproduit par l’IFN-g, IDO etait exprimee par l’ensemble des lignees, comme le CMH-I et -II. PD-L1 etait induit chez les 7 lignees. On observait une augmentation de la production de CXCL9 et CXCL10. L’anti-IDO diminuait l’expression d’IDO et PD-L1 de facon dose-dependante. Il augmentait la reactivite des TILs pour 2 lignees de facon dose-dependante (M125 ; M301). Le statut BRAF influencait uniquement la production d’IL-6, production tres superieure pour les lignees mutees. Discussion Il s’agit du premier travail etudiant anti-IDO et TILs. Bien que l’anti-IDO puisse stimuler l’activite cytotoxique des TILs, ce mecanisme ne semble pas en lien avec la modulation d’expression de CMH-I et -II ni de PD-L1 par les cellules tumorales. En effet, malgre un profil d’expression similaire pour l’ensemble des lignees tumorales, l’anti-IDO n’a permis d’augmenter l’activite cytotoxique des TILs que pour deux lignees. L’excretion d’IL-6 serait induite par BRAF. Conclusion IDO est un mecanisme cle de l’immunotolerance. Son effet synergique sur les TILs apparait limite a certaines lignees tumorales, laissant supposer l’interet de definir le profil d’un sous-groupe de patients qui pourrait beneficier d’un anti-IDO. Cette notion de sous-groupe peut aussi expliquer l’absence de benefice d’un anti-IDO dans le cadre d’un essai de phase III associant anti-IDO et anti-PD-1 realise sur une large population de melanomes metastatiques.

is missing (Short communication)

Introduction Le terme d’hamartome conjonctif (HC) - connective tissue naevus - fait reference a une lesion cutanee benigne circonscrite presentant histologiquement des anomalies du collagene (dermatofibrosis lenticularis disseminata), et/ou de l’elastine ou des glycosaminoglycanes. L’HC peut etre isole ou s’integrer dans un syndrome de Buschke–Ollendorff, maladie genetique rare due a des mutations constitutionnelles du gene LEMD3, comprenant egalement des lesions osseuses (osteopoecilie). Nous rapportons chez plusieurs enfants, une presentation clinique stereotypee et non rapportee au prealable au cours des HC, a type de tumeur bosselee de la racine d’un membre. Observations Il s’agissait de 7 enfants : 4 filles et 3 garcons, âges de 3 a 16 ans, adresses pour suspicion de sclerodermie cutanee. Tous presentaient une large tumeur en plaque (15 cm), situee au niveau de la racine d’un membre (membre inferieur : n = 6 (racine de la cuisse, hanche et fesse), membre superieur : n = 1). La tumeur etait bosselee en surface, cartonnee et non plissable a la palpation. La lesion etait congenitale ou constatee dans les premieres annees de vie. L’evolution se faisait vers une stabilite (n = 3) ou une augmentation lente de la fermete (n = 4). La gene fonctionnelle etait moderee. Un seul cas presentait une histoire familiale d’HC. La biopsie revelait un derme epaissi avec une proliferation du collagene isolee (n = 3) ( Fig. 1 et 2 ) ou associee a des anomalies de l’elastine (n = 4). Les radiographies osseuses realisees chez 4 enfants etaient normales. L’IRM realisee chez 3 enfants montrait des anomalies dermo-hypodermiques sans anomalie musculaire ou osseuse. Des analyses genetiques sont en cours (notamment pour le gene LEMD3). Discussion Selon la classification de Uitto, nos cas correspondent a un HC collagenique ou mixte. Cette presentation stereotypee a type de tumeur bosselee de la racine d’un membre n’y est pas rapportee. Dans la litterature, nous n’avons retrouve qu’un seul cas d’HC collagenique de la racine du membre inferieur chez un enfant, etiquete « zosterifome ». Cette presentation clinique stereotypee doit etre connue afin de ne pas porter a tort le diagnostic differentiel de sclerodermie cutanee et realiser des examens inutiles. L’etiopathogenie de cet HC a type de tumeur de la racine d’un membre est meconnue : possible mosaique genetique (gene LEMD3 ou autre gene). Il convient d’evoquer un syndrome de Buschke–Ollendorff et de realiser des radiographies osseuses, voire une analyse moleculaire. Conclusion Cette presentation clinique stereotypee d’HC a type de tumeur bosselee induree de la racine d’un membre est importante a reconnaitre.

Introduction Les mycobacteries atypiques (MA) sont responsables chez l’enfant immunocompetent d’adenites cervico-faciales dont l’incidence serait en augmentation depuis l’arret de la vaccination systematique par le BCG en 2007. L’objectif etait de decrire les caracteristiques cliniques, microbiologiques et therapeutiques de cette pathologie. Materiel et methodes Etude retrospective monocentrique recensant les cas recus entre janvier 2008 et decembre 2017 dans un CHU. Criteres d’inclusion âge Resultats De 2008 a 2017, 49 patients ont ete inclus : 31 filles, 18 garcons. L’âge moyen etait de 37 mois (6–141). Le delai diagnostique moyen etait de 3,5 mois (1,53–7,57). Seuls deux enfants sur 39 enfants etaient vaccines par le BCG. Les localisations etaient cervicales = 16/49 (33 %) ; parotidiennes = 8/49 (16 %) ; sous-mandibulaires = 22/49 (45 %), non precisees = 3/49 (6 %). Les principaux signes cliniques etaient la presence d’un nodule ferme (19/27, 70 %), violace (13/22, 59 %), non douloureux (19/23, 83 %) sans fievre (29/33, 88 %). Les especes identifiees etaient : Mycobacterium avium (n = 26), M. lentiflavum (n = 13), M. intracellulare (n = 7), M. malmoense (n = 2), M. scrofulaceum (n = 1). Sur le plan therapeutique 30/39 (77 %) patients ont beneficie d’une antibiotherapie associee a une chirurgie dans 39 % des cas (15/39) ; 6/39 d’une chirurgie seule et 3/39 d’une abstention therapeutique. L’evolution etait favorable pour l’ensemble des cas, sans aucune recidive rapportee. Discussion Il s’agit de la deuxieme plus grande cohorte francaise d’adenites a MA de l’enfant confirmees microbiologiquement. La presentation la plus frequente etait celle d’un nodule ferme, violace, non fistulise et indolore, apres etude d’une population homogene sur une duree de 10 ans. L’espece predominante etait M. avium. Une antibiotherapie etait prescrite dans plus de 75 % des cas (macrolides), avec ou sans chirurgie (qui reste le traitement de reference notamment dans les recommandations americaines ATS/IDSA 2007) et pour les cas les plus recents une tendance a l’abstention therapeutique. De nombreux cas sont probablement non diagnostiques par manque de sensibilite des methodes diagnostiques. L’emergence de M. lentiflavum observee dans notre etude n’est pas retrouvee dans les grandes series europeennes d’avant 2014 mais apparait dans les series plus recentes. L’influence de l’arret de la vaccination par le BCG sur la l’incidence des adenites a mycobacteries atypiques n’est pas statistiquement demontrable dans notre etude en raison du manque de donnees anterieures a 2007. Il est a prendre en compte que l’effet protecteur de la vaccination a ete demontre sur modele animal. Conclusion L’adenite a MA est un diagnostic a ne pas meconnaitre chez le jeune enfant devant une tumefaction cervico-faciale violacee indolore.

The Large Hadron Collider (LHC) contains eight main dipole circuits, each of them with 154 dipole magnets powered in series. These 15-m-long magnets are wound from Nb-Ti superconducting Rutherford cables, and have active quench detection triggering heaters to quickly force the transition of the coil to the normal conducting state in case of a quench, and hence reduce the hot spot temperature. During the reception tests in 2002-2007, all these magnets have been trained up to at least 12 kA, corresponding to a beam energy of 7.1 TeV. After installation in the accelerator, the circuits have been operated at reduced currents of up to 6.8 kA, from 2010 to 2013, corresponding to a beam energy of 4 TeV. After the first long shutdown of 2013-2014, the LHC runs at 6.5 TeV, requiring a dipole magnet current of 11.0 kA. A significant number of training quenches were needed to bring the 1232 magnets up to this current. In this paper, the circuit behavior in case of a quench is presented, as well as the quench training as compared to the initial training during the reception tests of the individual magnets.

The knowledge of the critical current density in a wide temperature and applied magnetic field range is a crucial issue for the design of a superconducting magnet, especially for determining both current and temperature margins. The critical current density of LHC-type Nb-Ti strands of 0.82 and 0.48 mm diameter was measured by means of critical current and magnetization measurements at both 4.2 K and 1.9 K and for a broad magnetic field range (up to 11 T). For the magnetic field range common to both measurement methods, critical current density values as extracted from transport current and from magnetization data are compared and found fairly consistent. Our experimental data are compared to other sets from literature and to scaling laws as well

The Nb-Ti hard conductors used in LHC dipole and quadrupole magnets are Rutherford cables composed of several tens of strands. During the cabling process, the strands are severely compacted especially at the thin edge of the cable. In order to assess, on the whole wire length, the deformation effect on the transport current of the wires, LHC-type Nb-Ti superconducting strands of various types were flattened by means of rollers. The critical current was then measured as a function of deformation and applied magnetic field at both 4.3 K and 1.9 K. The measurements were performed for both orientations (flat face perpendicular or parallel to magnetic field). The critical current density anisotropy of such deformed strands and the correlation with magnetization effects are discussed. This study permits to better understand and to quantify the critical current degradation of few percent observed in strands due to cabling. Comparisons with wires extracted from Rutherford cables are presented

Introduction Les anti-PD-1 font parties des immunotherapies utilisees dans le traitement du melanome metastatique. Leurs effets secondaires cutanes sont frequents (environ 30 %, rash maculopapuleux et prurit majoritairement). Nous rapportons le cas original d’un patient traite par nivolumab, ayant presente a la deuxieme perfusion un erytheme polymorphe majeur. Observation Un homme de 67 ans etait suivi pour un melanome de stade IV de primitif lingual BRAF sauvage avec cibles ganglionnaires et cutanees. Il avait pour principal antecedent un syndrome metabolique. Suite a une progression sous ipilimumab n’ayant induit aucun effet secondaire, il avait ete decide un traitement par nivolumab (anti-PD-1) a la dose de 3 mg/kg tous les 15 jours. Vingt-quatre heures apres la deuxieme perfusion, le patient presentait une eruption erythemato-papuleuse avec cocardes et une atteinte des muqueuses sans atteinte oculaire ni fievre. Il n’etait pas trouve d’autre prise medicamenteuse recente. Les PCR virales (HHV6, parvovirus B19, CMV, EBV et HSV 1–2) etaient negatives ainsi que la serologie mycoplasme. Le bilan biologique montrait un syndrome inflammatoire modere (CRP a 22,8 mg/L ; N Discussion Les anti-PD-1 sont des traitements tres prometteurs qui ont fait leurs preuves dans le melanome metastatique. Des reactions d’hypersensibilite ont deja ete rapportees sous forme de rashs cutanes mais a notre connaissance, les toxidermies bulleuses n’ont jamais ete decrites. La question soulevee par ce cas est celle de la reintroduction du traitement, avec d’un cote le risque d’une toxidermie plus severe (syndrome de Stevens-Johnson, voire de Lyell) et de l’autre le controle de la maladie metastatique. Conclusion Nous rapportons le premier cas original d’un erytheme polymorphe majeur sous anti-PD-1. Notre observation montre qu’un tableau d’erytheme polymorphe justifie d’un arret definitif de l’anti-PD-1.

Six contracts have been placed with industrial companies for the production of 1200 tons of the superconducting (SC) cables needed for the main dipoles and quadrupoles of the Large Hadron Collider (LHC). In addition, two contracts have been placed for the supply of 470 tons of NbTi and 26 tons of Nb sheets. The main characteristic of the specification is that it is functional. This means that the physical, mechanical and electrical properties of strands and cables are specified without defining the manufacturing processes. Facilities for the high precision measurements of the wire and cable properties have been implemented at CERN, such as strand and cable critical current, copper to superconductor ratio, interstrand resistance, magnetisation, RRR at 4.2 K and 1.9 K. The production has started showing that the highly demanding specifications can be fulfilled. This paper reviews the organisation of the contracts, the test facilities installed at CERN, the various types of measurements and the results of the main physical properties obtained on the first batches. The status of the deliveries is presented.

In the superconducting main magnets of the Large Hadron Collider (LHC), persistent currents in the superconductor determine the field quality at injection field. For this reason it is necessary to check the magnetization of the cable strands during their production. During four gears, this requires measurements of the width of the strand magnetization hysteresis loop at 0.5 T, 1.9 K, at a rate of up to eight samples per day. This paper describes the design, construction and the first results of a magnetization test station built for this purpose. The samples are cooled in a cryostat, with a 2-m long elliptic tail. This tail is inserted in a normal conducting dipole magnet with a field between /spl plusmn/1.5 T. Racetrack pick-up coils, integrated in the cryostat, detect the voltage due to flux change, which is then integrated numerically. The sample holder can contain eight strand samples, each 20 cm long. The test station operates in two modes: either the sample is fixed while the external field is changed, or the sample is moved while the field remains constant, First results of calibration measurements with nickel and niobium are reported.

When using superconducting magnets in particle accelerators like the LHC, persistent currents in the superconductor often determine the field quality at injection, where the magnetic field is low. This paper describes magnetization measurements made on LHC cable strands at the Technical University of Vienna and the Institute of Physics of the Polish Academy of Sciences in collaboration with CERN. Measurements were performed at T=2 K and T=4.2 K on more than 50 strands of 7 different manufacturers with NbTi filament diameter between 5 and 7 micrometer. Two different measurement set-ups were used: vibrating sample magnetometer, with a sample length of about 8 mm, and an integrating coil magnetometer, with sample length of about 1 m. The two methods were compared by measuring the same sample. Low field evidence of proximity effect is discussed. Statistics like ratio of the width of the magnetization loop at 4.2 K 2 K, and the initial slope dM/dB after cooldown are presented. Decrease of the magnetization with time, of the order of 22d8d8er hour, was observed in some samples. (5 refs).and

Un dispositif experimental, pour mesurer les pertes generees dans les conducteurs supraconducteurs utilises en regime alternatif 50 Hz, est decrit. La methode, basee sur le principe thermometrique, consiste a isoler l'echantillon du bain d'helium par une resistance thermique. La puissance dissipee est determinee a l'aide de deux sondes de temperature disposees de part et d'autre de la resistance. L'etalonnage de la mesure est assure par une chaufferette. La precision des mesures est de 10% pour des pertes lineiques superieures a 2 mW/m.

The current distribution and also AC losses, in a multifilamentary superconductor carrying a transport current, are influenced by the self and the external magnetic field. By using the Maxwell equations, a model has been developed in order to calculate the temporal evolution of current distribution in a single wire exposed or not to external magnetic field. This model is based on the actual relationship of electrical field E with current density J and takes into account the twist pitch of the wire. AC losses are calculated by adding all local losses through the cross section. This paper presents calculations of the influence of the cable twist coupled with the longitudinal magnetic field, and also gives some ideas how to decrease losses.

Applications of 50 Hz superconductors like the transformer and the fault current limiter correspond to relatively low magnetic fields, so that AC losses and stability are mainly governed by the conductor self field. AC loss calculations as they are performed in most cases for superconductors, are based on the Bean critical state model which states that everywhere in a superconductor, the current density has a modulus equal to the critical current density J/sub c/. This model is applicable when the superconducting transition E(J) is very sharp, but sizeable discrepancies appear for 50 Hz superconductors, as they present a relatively smooth superconducting transition. AC loss calculations have been developed using the Maxwell equations combined with the actual E(J) relationship. The heat generation in the conductor is then used as an input for a numerical calculation of the temperature distribution through the superconductor. The stability limits are directly derived from the thermal model. >

Fast cycled superconducting magnets (FCM's) are an option of interest for the long-term consolidation and upgrade plan of the LHC accelerator complex. In the past two years we have conducted an R\&D targeted at investigating the feasibility, operational issues and economical advantage of FCM's in the range of 2 T bore field, continuously cycled at 1 Hz. In this paper we report the main results on the development of strands and cables suitable for this application, providing details on the strands tested and the cable manufacturing and performance.

The LHC is an accelerator with unprecedented complexity where the energy stored in magnets and the beams exceeds other accelerators by one-to-two orders of magnitude. To ensure a safe and efficient machine start-up without being plagued by technical problems, a phase of "hardware commissioning" was introduced: a thorough commissioning of technical systems without beam. This activity started in June 2005 with the commissioning of individual systems, followed by operating a full sector, one eighth of the machine; the commissioning is expected to last until spring 2008 when commissioning with beam will start. The LHC architecture allows the commissioning of each of the eight sectors independently from the others, before the installation of other sectors is complete. An important effort went into the definition of the programme and the organization of the coordination in the field, as well as in the preparation of the tools to record and analyze test results. This paper discusses the experience with this approach, presents results from the commissioning of the first LHC sector and gives an outlook for future activities.

The production of more than 60% of superconducting cables for the main dipoles of the Large Hadron Collider has been completed. The results of the measurements of cable magnetization and the dependence on the manufacturers are presented. The strand magnetization produces field errors that have been measured in a large number of dipoles (approximately 100 to date) tested in cold conditions. We examine here the correlation between the available magnetic measurements and the large database of cable magnetization. The analysis is based on models documented elsewhere in the literature. Finally, a forecast of the persistent current effects to be expected in the LHC main dipoles is presented, and the more critical parameters for beam dynamics are singled out.

Recently several Rutherford-type Nb Sn cables for possible use in new magnets for upgrades of the LHC have been measured at CERN. A summary is provided including a comparison of the critical current (Ic) of various cable types and strand materials versus their respective extracted strand measurements. The conductors were cabled at CERN and Lawrence Berkeley National Laboratory. The summary shows an unsurprising linear relation between the strand and the cable performance. However, assuming that the local peak magnetic field in the conductor is the relevant factor for determining the Ic(B) relation, a discrepancy is found when results from different directions of applied magnetic field on the cable are compared. In this paper it is shown that the critical current as a function of the peak magnetic field in the conductor can change in the range of 7-12% depending on the direction of the applied magnetic field. This effect originates from the superposition of the self field of the conductor and the applied magnetic field. When the direction of the applied magnetic field is changed, the position of the peak magnetic field in the conductor shifts. Mechanical degradation during the cabling process can create a local reduction in the critical current. When the position of the peak magnetic field shifts from a more degraded to a less degraded area, the measured Ic(B) curve of the conductor will change accordingly. The measured effect is in principle present in all cables exhibiting non-uniform cabling degradation but is substantially present in Nb3Sn conductors for the reasons mentioned.