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The shipping industry is directly impacted by the global challenge of reducing greenhouse gas emissions. Improvements can be achieved by hull form optimization when designing new ships. Computational Fluid Dynamics (CFD) is nowadays regularly applied for basic resistance simulations as well as for e.g. self-propulsion with rotating propellers or maneuvering in waves. In order to avoid scale-effects, it is increasingly common to perform ship scale CFD calculations. Unfortunately, the available full scale data that can be used for validation are limited. Specifically, flow velocity and radiated wave pattern data are rare at full scale because of the complexity of performing such measurements. Nevertheless, in the current work, full scale wave pattern measurement were performed on a 330 meter long cruise ship sailing at 20 knots using the Digital Image Correlation technique. This is an image analysis method capable of measuring deformations of a surface in space. The approximate size of the field of view was 75 m by 30 m. The ship’s speed, shaft power, propeller rate, motions and environmental waves were measured as well. Additionally, Reynolds Averaged Navier-Stokes (RANS) simulations were performed using STARCCM+. The propeller was modelled both as an actuator disk as well as a rotating propeller with a sliding interface. The turbulence closure model was k-ω SST and the free surface was modelled using the Volume of Fluid method. The balance between hull resistance and propeller thrust was verified as a first step, showing less than 4.0% difference. The power determined by CFD was validated against the one measured during the sea trials with less than 3.6% difference. Finally, the comparison of the stern wave pattern resulting from full scale CFD simulations with the pattern measured using DIC showed excellent agreement with good accuracy.

International audience; ObjectivesWe aimed to investigate the first Omicron cases detected in France in order to assess case characteristics and provide supporting information on the possible impact of this variant on the healthcare system.MethodsA standardized questionnaire was used to collect information from confirmed and probable Omicron cases.ResultsMedian age of 468 investigated cases was 35 years, 376 were symptomatic (89%); 64% were vaccinated with two doses and 7% had received three doses. Loss of smell and taste were reported by 8.3% and 9% of cases, respectively. Seven cases were hospitalized, three of those were unvaccinated (including two with reported precondition). No admissions to intensive care and no deaths were reported.ConclusionsOur results confirm a mild clinical presentation among the first Omicron cases detected in France and highlight the importance for the national COVID-19 surveillance system to quickly detect and adapt to the emergence of a new variant.

A new method for sampling virtual experiments on the initial yield surface is introduced for the plane stress state. The method is based on a machine learning technique called active learning, which can be used to adaptively sample a parameter space with respect to a certain criterion. For the evaluation of this new method, it is compared against a random sampling approach taken from literature and the effect of both methods on three different anisotropic yield models, namely Yld89, Yld2000-2d and Yld2004-18p (in-plane), is analysed. The results demonstrate that the active learning based sampling approach has advantages over the random sampling approach in terms of reliability and sample efficiency. Moreover, it is found that the effect of the sampling method on the resulting yield surface depends on the anisotropic yield model considered.

Introduction Les anticorps anticytoplasme des polynucleaires neutrophiles ou ANCA ont permis, par leur association, de caracteriser des vascularites necrosantes de petits vaisseaux. Ils sont toutefois aussi retrouves dans des maladies non vascularitiques. L’objectif est de decrire ces entites non vascularitiques associees aux ANCA positifs et identifier leur significativite en termes pronostics. Materiels et methodes Cette etude observationnelle, realisee dans un centre hospitalier tertiaire, s’est interessee retrospectivement au registre de patients adultes (> 18 ans) identifies via leur positivite pour les ANCA sur une periode de 01/01/2010 au 31/12/2018. Ces patients etaient classes en fonction de leur diagnostic de vascularite (ANCA/V + ) ou l’absence de manifestation vascularitique au diagnostic (ANCA/V-), et a 3 mois du dosage initial d’ANCA. Les caracteristiques demographiques entre ces 2 groupes etaient comparees. Pour le groupe ANCA/V-, les caracteristiques cliniques et diagnostics associes etaient decrits. On recherchait aussi l’evolution vers une vascularite, les modifications du taux d’ANCA, la survie jusqu’a 5 ans et les formes de connectivites associees. Resultats Deux cent quatre-vingt dix-neuf patients etaient etudies sur une cohorte de 321 patients au moment de la soumission. Il n’y avait pas de difference des sexe-ratios entre les 2 groupes, mais les sujets ANCA/V- etaient plus jeunes (55,0 ± 1,2 vs. 66,3 ± 1,8 ans, p Conclusion Une positivite des ANCA, notamment de specificite anti-PR3, accompagnant des presentations cliniques non vascularitiques ne semble pas etre un marqueur d’evolutivite vers une vascularite necrosante. Les ANCA/V- sont grevees d’une mortalite de moins de 5 % a 5 ans et la recherche de maladie associee amene a identifier une connectivite dans moins de 15 % des cas.

Introduction L’anemie hemolytique auto-immune (AHAI) est une entite rare dont le pronostic est intimement lie a la maladie associee des formes secondaires. L’AHAI du patient reanimatoire est mal documentee et s’accompagne d’un taux de mortalite eleve. L’interet des echanges plasmatiques (EP) est controverse et est difficilement etudiable dans la maladie des agglutinines froides (MAF) d’evolution fulminante. Observation Nous rapportons le cas d’un patient de 75 ans, sans comorbidite, qui a presente un livedo racemosa interessant l’ensemble de la peau, avec une splenomegalie et un ictere a bilirubine libre. On notait un phenomene de Raynaud apparu 3 ans auparavant. Le patient est pris en charge en reanimation pour l’installation d’une insuffisance renale KDIGO 3 et l’inefficacite d’une corticotherapie sur l’hyperhemolyse et la profondeur d’une AHAI a anticorps froids anti-C3d. Un pic monoclonal IgMk de 3,6 g/L est identifie dans un contexte de cryoglobulinemie de type I, et l’absence d’anomalie du complement. L’immunophenotypage caracterise une macroglobulinemie de Waldenstrom. Il n’est pas trouve d’argument pour une origine infectieuse ni pour une connectivite. Le patient necessitait une epuration extrarenale (EER) qui est realisee avec un rechauffement et une intensification de la corticotherapie. Devant la mauvaise tolerance cardiocirculatoire de l’anemie et des dysfonctions du circuit d’hemodialyse attribuees aux entites associees a l’IgMk monoclonale, une premiere serie d’EP selon un schema j1–j2–j5 est pratiquee pour encadrer le support transfusionnel erythrocytaire. Le fluide de substitution etait de l’albumine 4 % avec une masse plasmatique de 1–1,5. Le rendement transfusionnel est ameliore parallelement a l’amendement en 24 h des stigmates d’hemolyse intravasculaire. Le rituximab (RTX) est initie a j5 (=j1 RTX) et sera associe a la bendamustine (j2–j3 du RTX) et l’ibrutinib quotidien. La reticulocytose etant indosable, de la darbepoetine alfa est instauree. A j15, une rechute de l’AHAI est constatee, suivie d’une epistaxis compliquee de choc hemorragique attribuable a l’ibrutinib. Une hypofibrinogenemie aggravee par les EP est eliminee. Une 4e seance d’EP permettra une reponse hematologique transitoire. L’EER est sevree devant l’amelioration de l’insuffisance renale liee a la probable necrose tubulaire aigue. Sur une periode d’un mois, le patient aura recu 19 CGR et 3 PFC. L’evolution sera marquee par le caractere refractaire de la cytopenie et le deces du patient de choc septique deux mois plus tard malgre les traitements anti-infectieux prophylactiques. Discussion L’hemolyse hyperaigue dans le contexte de MAF est exceptionnelle mais engendre une morbidite importante surtout quand elle s’accompagne de defaillance aigue d’organe. La therapie medicamenteuse consiste en du RTX et son association avec une chimiotherapie du lymphome. La corticotherapie et la splenectomie sont inefficaces. Le recours aux EP se justifie dans les cas d’hemolyse fulminante, relevant de support transfusionnel et/ou dans l’attente d’une efficacite des traitements immunosuppresseurs. Cette logique repose sur la clairance des auto-anticorps, complexes immuns et fractions du complement circulants. Dans la MAF, l’hemolyse chronique est surtout intratissulaire. L’utilisation des EP porte ainsi sur l’activite hemolytique des IgM circulantes. L’amplitude thermique des auto-IgM peut etre telle que l’agglutination dans le circuit extra-corporel impose le recours aux EP, chez des patients necessitant une EER comme cela a ete le cas pour notre patient. Les etudes sur l’utilisation des EP dans les AHAI severes se limitent a des petites series retrospectives et d’etudes de cas. Il semble important de distinguer l’efficacite aleatoire des EP rapportee dans les AHAI a anticorps chauds (mais mieux decrites), des cas de defaillances d’organe dans la MAF qui pourraient beneficier de la reponse, certes transitoire, de cette technique. Par ailleurs, on privilegiera des anti-neoplasiques d’action rapide en limitant les produits induisant des saignements. La perfusion de plasma doit etre tres limitee car elle pourrait, en theorie, entretenir l’hemolyse par l’apport de C3 et C4. Les traitements tels que le bortezomib ou eculizumab ne sont que de recours exceptionnel et mis en balance avec le risque infectieux majeur preexistant. Conclusion Les EP constituent un choix therapeutique interessant dans la gestion de l’hemolyse hyperaigue et de defaillance d’organe de ces formes exceptionnelles de MAF fulminantes. Une meilleure comprehension de leur place dans cette pathologie pourra etre apportee par le recours a un appel a observations.

Introduction L’amylose AL est une maladie de depots extracellulaires de chaines legeres libres d’immunoglobulines pouvant, dans sa forme systemique, induire des defaillances d’organes multiples. Nous rapportons le cas d’un patient presentant une polyglobulie (PG) au diagnostic de la maladie, une manifestation peu decrite dans ce contexte. Observation Un patient de 69 ans, sans antecedent particulier, est pris en charge pour une alteration de l’etat general dans le contexte d’une amylose hepatique « AL » caracterisee histologiquement. Il presente une hypotension arterielle (85/48 mmHg) et une hypothermie a 34,8 °C au diagnostic. On precise l’absence d’obesite, de tabagisme et d’insuffisance respiratoire chronique. L’examen clinique trouve des signes de deshydratation globale chez un sujet icterique avec une hepatosplenomegalie. L’echocardiographie transthoracique montre un aspect brillant du muscle cardiaque avec une hypertrophie parietale. La biologie permet de classer l’attente cardiaque en stade 3 de Mayo Clinic (troponine a 758 ng/l et BNP a 788 pg/ml). Il existe un profil glomerulaire de l’atteinte renale. Le bilan hepatique trouve des ASAT 152 U/L, ALAT 110 U/L, GGT a 1492 U/L, PAL 1111 U/L et s’accompagne de troubles de l’hemostase (TP a 66 %, TCA a 57 s, Facteur X a 63 %) sans argument pour une coagulation intravasculaire disseminee. L’hemogramme montre un hematocrite a 51 % (taux d’hemoglobine a 203 g/L) sans anomalie de la formule leucocytaire ou des plaquettes. L’electrophorese et l’immunofixation des proteines seriques et urinaires revelent une bande monoclonale kappa. Le ratio des chaines legeres kappa/lambda est de 43,7 avec un dFLC a 783. Le myelogramme fera le diagnostic de myelome multiple avec 12,5 % de plasmocytes et sera classe en stade III R-IPSS. Une origine secondaire de la PG est suspectee au vu du contexte. De principe, on dose l’erythropoietine (EPO) a 12,3 mU/mL (normal). La recherche de mutation de JAK2 et de CALR est rendue negative–et argumente en defaveur d’un syndrome myeloproliferatif (SMP) chronique associe a l’amylose. L’optimisation de l’hydratation et l’ajustement des diuretiques de l’anse permettront de normaliser l’hematocrite. Le patient decedera quelques jours plus tard de defaillances d’organes multiples. Discussion La signification de la PG n’est pas precisee au cours des amyloses AL systemiques. Sa description dans la litterature semble predire la defaillance multi-organe [1] , [2] , [3] . Plusieurs hypotheses mecanistiques ont ete proposees dont une reduction du volume extracellulaire lie a un hyposplenisme ou a la dysautonomie [1] . L’impact des cytokines et facteurs de croissance (i.e. IL-3, IL-6, EPO) sur les progeniteurs erythroblastiques a aussi ete evoque et attribue aux atteintes renales, hepatiques et spleniques de l’amylose systemique [1] . Plus recemment, l’association de SMP a la pathologie amyloide a ete decrite avec une majorite de cas de polyglobulie de Vaquez [3] . Elle s’accompagne d’un taux de mortalite plus importante et une moindre reponse au traitement. Son taux de prevalence est inferieur a 2,5 % des cas d’amylose AL [3] . Dans le present cas, le mecanisme privilegie est l’association de dysautonomie et de deshydratation. Le frottis sanguin ne trouvait pas de dysmorphie erythrocytaire et il n’existait pas de stigmate de SMP. Il n’y avait pas d’argument pour une thrombose des arteres renales ou autre processus stimulant la secretion d’EPO. Conclusion L’association de PG et d’amylose systemique, quel que soit son mecanisme, est rarement decrite. Elle apparait comme un potentiel facteur pronostique pejoratif qui necessite d’etre mieux evalue.

Introduction Le purpura thrombotique thrombocytopenique (PTT) est une microangiopathie thrombotique (MAT) grave responsable de defaillance multi-organe en l’absence de therapeutique. Il peut etre associe a des connectivites dont le syndrome Sjogren primitif (SSp). Nous rapportons le cas d’une patiente suivie pour un SSp et presentant une rechute precoce de PTT malgre un traitement optimal au diagnostic. Observation Une femme de 49 ans, sans antecedent particulier en dehors d’un SSp sans facteur d’evolutivite depuis 20 ans, s’est presentee aux urgences pour des troubles neurologiques, arthralgies et un syndrome hemorragique depuis 24 heures. On ne note pas d’episode infectieux ou de nouveau traitement introduit. La fonction renale n’est pas alteree et le dosage de la troponine Ic est normal. L’IRM cerebrale montre l’absence d’anomalie. Le diagnostic de MAT amene a une prise en charge en secteur de reanimation et a l’initiation d’echanges plasmatiques (EP) quotidiens avec 1,5 de volume plasmatique total substitue a chaque seance. On caracterisera le PTT par l’effondrement de l’activite ADAMTS13 et le dosage d’anticorps anti-ADAMTS13 supra-seuil (> 100 UI/mL). Le SSp repondait aux criteres de classification et ne relevait jusqu’a l’episode de MAT d’aucun traitement. On precise la positivite des facteurs antinucleaires avec la presence d’anti-SSA. La patiente recoit une corticotherapie a 1 mg/kg/j et de l’hydroxychloroquine a 6,5 mg/kg/j y est associee. Au vu de l’association de SSp au PTT, un traitement par rituximab est administre a 375 mg/m2 selon un schema j1, j4, j8, j15 (PTT-RTX 1) sans intervalle libre depuis le debut des EP. L’examen clinique se normalise a j2 de prise en charge. La thrombopenie et les LDH se corrigent a j4 chez une patiente restant asymptomatique. Les EP sont ainsi arretes sur les criteres de reponse biologique classique. A j7 de prise en charge, la thrombopenie reapparait et l’anemie s’aggrave avec la reapparition de schizocytes. Les EP quotidiens sont reinities et progressivement espaces (au total 16 EP) suite a une reponse biologique. La remission est maintenue apres un recul de 2 mois. Discussion Le SSp est la connectivite la plus frequemment associee au PTT (SSp-PTT) apres le lupus erythemateux systemique (LES). Tres peu d’etudes se sont interessees a caracteriser les patients avec SSp et MAT [1] , [2] . Les quelques donnees disponibles montrent l’absence de manifestation extraglandulaire ou de facteurs de risque d’evolution vers une maladie lymphomateuse [1] . Si le risque de maladie auto-immune a bien ete decrit et correle a la presence d’anti-SSA et anti-ADN natif au diagnostic de PTT, les donnees de la litterature sont insuffisantes pour caracteriser la reponse therapeutique dans les SSp-PTT. Certaines etudes ont evoque un pronostic plus sombre dans les PTT satellites de LES [3] . Les strategies therapeutiques n’ont pas ete etudiees et sont classiquement adaptees a la reponse therapeutique initiale. L’hydroxychloroquine ne semble pas prevenir le PTT [1] , [3] . Il existe une tendance a l’augmentation du taux de reevolutivite precoce dans les SSp-PTT comparee au PTT idiopathique seul [2] . Le traitement par rituximab, ayant deja prouve son efficacite dans les PTT auto-immuns refractaires par une action de depletion des lymphocytes B auto-reactifs producteurs d’anticorps anti-ADAMTS13, semble justifie dans la prise en charge precoce des SSp-PTT. Conclusion Le SSp-PTT est un evenement rare dans le cadre d’un SSp et releve d’une therapeutique precoce par rituximab au vu du potentiel evolutif potentiellement plus important que les formes de PTT non associees aux connectivites. De futures etudes sur les MAT permettront de mieux caracteriser l’histoire naturelle du SSp-PTT.

Introduction L’hypertension arterielle pulmonaire (HTAP) associee aux connectivites est une pathologie rare, compliquant classiquement la sclerodermie ou le lupus systemiques. Son association avec le syndrome de Sjogren primitif (SSp) (HTAP-SSp) et la reponse au traitement immunosuppresseur (IS) sont moins bien decrites. Nous rapportons le cas d’une HTAP-SSp grave et son evolution sous IS. Observation Une patiente de 24 ans, sans antecedent, se presente aux urgences pour une dyspnee stade NYHA 3, non febrile, evoluant depuis un mois. L’examen clinique identifie des signes d’insuffisance cardiaque droite avec une deviation axiale droite a l’ECG. L’echocardiographie objective une fraction d’ejection ventriculaire gauche conservee, et evalue une pression arterielle pulmonaire systolique (PAPs) a 70 mmHg, sans dilatation des cavites cardiaques. L’angioscanner thoracique et la scintigraphie de ventilation-perfusion pulmonaire ont permis d’eliminer une maladie thromboembolique veineuse. Le diagnostic d’HTAP est pose avec un catheterisme cardiaque droit (KtD) montrant des PAPs/d-m : 90/31–53 mmHg, des resistances vasculaires pulmonaire (RVP) a 9,8 UI Wood et un debit cardiaque (DC) a 4,19 L/min. Le test de reversibilite au NO est negatif. Le bilan etiologique met en evidence une positivite des facteurs antinucleaires a 1/1280 et avec la presence d’anti-SSA-52, SSA-60, et SSB. La fraction C4 du complement est effondree. Les criteres de classification pour le SSp sont verifies avec la caracterisation d’une sialadenite de grade 4. La serologie VIH est negative, pas de prise d’anorexigene. En traitement d’une HTAP-SSp, une corticotherapie a 1 mg/kg/j de prednisone est associee a une immunosuppression par mycophenolate mofetil (MMF) a 3 g/j en traitement adjuvant du sildenafil et macitentan aux doses usuelles. A 6 mois de traitement, le KtD montre une amelioration des parametres : PAPs/d-m a 39 mmHg, RVP a 5,6 UI Wood et un DC a 5,2 L/min. L’arret du traitement IS a cause d’intolerance digestive est suivi, 3 mois plus tard, d’une degradation de l’etat clinique (dyspnee NYHA 3) traduisant une aggravation des parametres de KtD : PAPs-d/m a 92/33–54 mmHg, des RVP a 9,8 UI Wood. La therapeutique est intensifiee par du cyclophosphamide a 500 mg tous les 15 jours faisant suite a un assaut corticoide de trois jours. Le traitement d’entretien associe une corticotherapie orale a la reprise du MMF. Le traitement anti-HTAP est modifie au profit de la combinaison tadalafil et macitentan. Cette derniere est renforcee secondairement par du selexipag devant la gravite de l’HTAP et l’aggravation de la dyspnee et pour permettre un sevrage progressif de l’immunosuppression. Toutefois, a 6 mois de l’arret de l’immunosuppression, on constate des PAPs/d-m a 98/34–60 mmHg et des RVP a 10,4 UI Wood faisant poser l’indication d’un traitement par prostacycline intraveineuse et discuter la reprise d’une immunosuppression. Discussion Du fait de sa rarete, l’HTAP-SSp est mal connue et sa prise en charge reste, a ce jour, mal definie [1] , [2] , [3] . L’interet du traitement IS est debattu a l’ere des traitements specifiques anti-HTAP mais semble trouver un rationnel via sa potentielle action sur la vasculopathie systemique, l’activation cellulaire B et l’auto-immunite [1] . Ce cas illustre la reponse physiologique aux IS comme en temoigne la degradation systematique de l’etat hemodynamique lors de l’arret de ce traitement, et cela malgre la poursuite des traitements anti-HTAP bien conduit. Plus recemment, l’instauration d’un traitement IS a ete decrite comme un facteur de bonne evolution chez les sujets presentant une HTAP-SSp. Conclusion L’HTAP est une complication rare du SSp pour laquelle les schemas therapeutiques restent mal codifies. Le traitement immunosuppresseur semble ameliorer les pronostics fonctionnel et vital et doit donc etre propose en premiere intention en association avec un traitement anti-HTAP.

To predict the quality of a process outcome with given process parameters in real-time, surrogate models are often adopted. A surrogate model is a statistical model that interpolates between data points obtained either by process measurements or deterministic models of the process. However, in manufacturing processes the amount of useful data is often limited, and therefore setting up a sufficiently accurate surrogate model is challenging. The present contribution shows how to handle limited data in a surrogate modeling approach using the example of a cup drawing process. The purpose of the surrogate model is to classify the quality of the drawn cup and to predict its final geometry. These classification and regression tasks are solved via machine learning methods. The training data is sampled on a relatively wide range varying three parameters of a finite element simulation, namely sheet metal thickness, blank holder force, and friction. The geometrical features of the cup are extracted using domain knowledge. Besides this knowledge-based approach, an outlook is given for a data-driven surrogate modeling approach.

Introduction En France, la prevalence de l’hepatite B chronique (HBC) est estimee a 0,65 % en population generale, soit 1 280 000 porteurs chroniques de l’AgHBs, dont 150 000 ignorent leur statut serologique. Le depistage, obligatoire en cas de grossesse ou de don de sang est egalement recommande de facon plus large pour les personnes de plus de 16 ans non vaccinees susceptibles d’etre exposees au virus de l’hepatite B. Les Centres gratuits d’information, de depistage et de diagnostic (CeGIDD) integrent le depistage et la prevention de l’HBC ainsi que l’orientation vers le soin des personnes positives. L’objectif de cette etude est de decrire la cascade de soins suite a un depistage positif de l’AgHBs dans un CeGIDD, afin d’identifier les etapes sur lesquelles agir pour ameliorer l’efficience de la prise en charge. Materiels et methodes Il s’agit d’une etude transversale menee entre 2016 et 2018 chez tous les patients consultant dans un CeGIDD et ayant beneficie d’un depistage de l’AgHBs. Les etapes de la cascade de soins ont ete decrites a partir du depistage jusqu’a la mise sous traitement des sujets ayant une indication a etre traites. Resultats Parmi les 5741 personnes depistees, la prevalence de l’AgHBs positif etait de 1,1 % (n = 63, IC95 % : 0,86–1,40), avec un sex-ratio de4, 25 et un âge moyen de 31 ans ± 11 ans. La majorite des sujets etait originaire d’Afrique Subsaharienne (n = 59, 93,7 %) et 30 d’entre eux (47,6 %) n’avaient aucune couverture sociale. Une co-infection VIH etait associee dans 3 cas (3,8 %) et aucune co-infection VHC n’etait notee. Parmi ces sujets avec AgHBs positif, 81 % (n = 51)ont recupere leurs resultats,61,9 % (n = 39/63) ont realise leur bilan initial et 60,3 % (n = 38/63)ont beneficie d’un suivi ulterieur. Au total, 39,6 % patients (soit 25/63 des sujets depistes positifs) ont ete consideres comme perdus de vue a une des etapes de la cascade de soins. Selon les recommandations Europeennes de traitement de l’HBC, 10 patients parmi les 39 sujets evalues devaient beneficier d’un traitement (hepatite B chronique AgHBe positif = 1, hepatite B chronique AgHBe negatif = 5, immunotolerant de plus de 30 ans = 1 et co-infection VIH = 3). Le traitement a effectivement debute pour 8 des 10 sujets eligibles(Tenofovir n = 5, Entecavir n = 2 et Interferon n = 1). Conclusion Notre etude a retrouve une prevalence de l’HBC deux fois plus elevee que dans la population generale en France, et environ 40 % des sujets depistes positifs n’ont pas integre la cascade de soin (en particulier a ses stades precoces). Ces donnees suggerent qu’il est important d’augmenter l’adhesion au soin apres un depistage en CeGIDD afin d’optimiser les differentes etapes de la prise en charge de l’HBC en France.

International audience

Introduction La positivite des anticorps antineutrophile cytoplasmatique (ANCA) est un phenomene rare dans les syndromes des Sjogren primitifs (SSp) et est associee a des manifestations systemiques extra-glandulaires. Nous rapportons le cas d’une patiente presentant une forme pneumo-renale non vascularitique de pSS a myeloperoxydase-ANCA (MPO-ANCA). Observation Une patiente de 74 ans, aux antecedents de nephropathie tubulo-interstitielle, a ete prise en charge pour une dyspnee chronique cotee mMRC 3, s’accompagnant d’une toux seche. Elle evoquait des arthralgies d’horaire inflammatoire et des dysesthesies en distalite de membre inferieur. L’examen clinique montrait des crepitants secs aux bases, une hypertrophie bilaterale des glandes lacrymales, et une eruption erythemateuse nodulaire transitoire. L’examen neurologique etait normal. L’anamnese precisait un syndrome sec oculo-buccal, secondairement objective par un test de Schirmer et de mesure de debit salivaire. Un scanner thoracique identifiait une fibrose interstitielle diffuse avec un pattern de pneumopathie interstitielle commune limitee. Sur le plan biologique, on trouvait un discret syndrome inflammatoire (CRP a 9,3 mg/L), une hypergammaglobulinemie polyclonale et une clairance de la creatinine a 57 mL/mn avec une hematurie microscopique. Le profil de l’insuffisance renale etait non glomerulaire avec une proteinurie des 24 h a 0,08 g/L n’amenant pas a considerer une biopsie renale. Le bilan immunologique montrait une positivite des MPO-ANCA (taux de 61 UA/mL) avec des facteurs antinucleaires negatifs. Un trouble ventilatoire restrictif mineur sans trouble de la diffusion du monoxyde de carbone etait identifie. L’electromyogramme des membres etait normal. L’etude anatomopathologique de biopsie de peau concluait a une perivasculite lymphocytaire pouvant s’integrer dans une connectivite de type lupus. La biopsie de glandes salivaires accessoires decrivait une sialadenite de grade 3 de Chisholm et Mason. L’analyse du liquide de lavage broncho-alveolaire rendait une formule lymphocytaire sans argument pour une hemorragie intra-alveolaire. Les criteres de classification ACR/EULAR 2016 pour un SSp etaient verifies. Les atteintes pulmonaire et renale etaient integrees a la connectivite. On ne retenait pas d’argument pour une vascularite a ANCA (VAA) en l’absence de critere clinique specifique. Discussion Il est estime que moins de 10 % des cas SSp s’accompagne d’une positivite des ANCA [1] . Ces derniers sont classiquement de specificite anti-MPO et semblent annoncer le caractere systemique et extra-glandulaire de la maladie [1] , [2] , [3] . Les atteintes extra-glandulaires les plus frequentes sont pulmonaires, articulaires et un phenomene de Raynaud [3] . De plus, pres de la moitie des cas d’atteinte renale presente des caracteristiques histologiques typiques de glomerulonephropathie de VAA [2] . L’atteinte tubulo-interstitielle, volontiers constatee dans les SSp, est difficile a distinguer des lesions renales debutantes de VAA. Aucun cas n’avait recours a un support par hemodialyse au diagnostic. Dans notre cas, la ponction-biopsie renale n’avait pas ete retenue en l’absence de proteinurie et la stabilite de la fonction renale. Dans les quelques series, la VAA succedait systematiquement a l’installation des manifestations systemiques de SSp associe aux ANCA [2] . L’evolution de la maladie sous traitement immunosuppresseur est generalement favorable. Notre patiente a recu une corticotherapie a 0,5 mg/kg/j de prednisone permettant l’amelioration de la symptomatologie respiratoire et de la spirometrie, et la regression des arthralgies. Conclusion Le SSp associe aux ANCA est rare et s’accompagne de manifestations systemiques extra-glandulaires qui precedent l’installation de VAA. Il releve d’une surveillance etroite tant sur le plan clinique que biologique du fait du risque d’evolution.

Summary HIV testing with rapid test can be used in the diagnosis of HIV infection, particularly in acute care settings. To evaluate the reliability of the Determine™ HIV-1/2 test used in routine laboratory conditions, we conducted a retrospective study on all rapid tests (n = 1429) performed at the Saint-Antoine hospital, between June 2002 and January 2010. The prevalence of HIV-1 positive patients was 2.7%. Among the positive patients, about two-thirds presented specific clinical symptoms of HIV infection. The Determine™ HIV-1/2 test has demonstrated a very high negative predictive value (NPV = 99.93%) and a lower positive predictive value (PPV = 82.98%). Our findings show a good performance of this rapid test in the hospital setting, with a relatively high prevalence of HIV infection. These results stress the lower sensitivity of rapid test than the antigen–antibody combination assay, at the time of primary HIV-1 infection and the risk of false positivity (0.56%) requiring preliminary information about some limitations of this test.

Objectives: To estimate the prevalence of transmitted drug resistance mutations and non-B subtype circulation in antiretroviral-naive chronically HIV-1-infected patients in France. Methods: Resistance mutations were sought in samples from 530 newly diagnosed HIV-1-infected patients from October 2006 to March 2007. Protease and reverse transcriptase mutations were identified from the 2007 Stanford Resistance Surveillance list. Results: Reverse transcriptase and protease resistance mutations were determined in 466 patients with duration of seropositivity

The spin structure functions g 1 for the proton and the deuteron have been measured over a wide kinematic range in x and Q 2 using 1.6 and 5.7 GeV longitudinally polarized electrons incident upon polarized NH3 and ND3 targets at Jefferson Lab. Scattered electrons were detected in the CEBAF Large Acceptance Spectrometer, for 0.05 Q 2 5 GeV 2 and W 3 GeV . The first moments of g 1 for the proton and deuteron are presented – both have a negative slope at low Q 2 , as predicted by the extended Gerasimov–Drell–Hearn sum rule. The first extraction of the generalized forward spin polarizability of the proton γ 0 p is also reported. This quantity shows strong Q 2 dependence at low Q 2 . Our analysis of the Q 2 evolution of the first moment of g 1 shows agreement in leading order with Heavy Baryon Chiral Perturbation Theory. However, a significant discrepancy is observed between the γ 0 p data and Chiral Perturbation calculations for γ 0 p , even at the lowest Q 2 .

The $e p\to e^\prime p \rho^0$ reaction has been measured, using the 5.754 GeV electron beam of Jefferson Lab and the CLAS detector. This represents the largest ever set of data for this reaction in the valence region. Integrated and differential cross sections are presented. The $W$, $Q^2$ and $t$ dependences of the cross section are compared to theoretical calculations based on $t$-channel meson-exchange Regge theory on the one hand and on quark handbag diagrams related to Generalized Parton Distributions (GPDs) on the other hand. The Regge approach can describe at the $\approx$ 30% level most of the features of the present data while the two GPD calculations that are presented in this article which succesfully reproduce the high energy data strongly underestimate the present data. The question is then raised whether this discrepancy originates from an incomplete or inexact way of modelling the GPDs or the associated hard scattering amplitude or whether the GPD formalism is simply inapplicable in this region due to higher-twists contributions, incalculable at present., Comment: 29 pages, 29 figures

Tenofovir disoproxil fumarate (TDF) has become an important component of HIV combination therapy because of its potency and once-daily dosing. Key mutation associated with resistance to TDF is a K65R in the reverse transcriptase (RT) gene. According to occurrence of K70E mutation after failure to TDF regimen, this mutation was recently reported as a mutation associated with TDF resistance in most resistance genotypic algorithms. The aim of this study was to analyze, retrospectively, the prevalence and conditions of selection of HIV-1 RT K70E mutation from a national clinical survey. Absence of selection of K70E in 850 HIV-1-infected naive patients suggests its role in NRTI drug resistance. Prevalence of K70E RT was low (99/41601, 0.24%) in patients treated between 1999 and 2005. Conversely with K65R mutation, thymidine analog mutations (TAMs) can be concomitantly observed with K70E mutation but its frequency decreased as the number of TAM increases. Concomitant association of K65R and K70E was possible but infrequent (11%). At the time of K70E selection, 60% of patients had received or received TDF-containing regimen and one-third received exclusive NRTI regimen. In conclusion, the K70E mutation could be an alternative pathway of TDF resistance, but as the K65R mutation, other NRTI as ABC, ddI, and 3TC could be also associated with the K70E selection.

The search for greater speed of analysis has fueled many innovations in high-performance liquid chromatography (HPLC), such as the use of higher pressures and smaller stationary-phase particles, and the development of monolithic columns. Alternatively, one might alter the chromatographic mobile phase. The low viscosity and high diffusivity of the mobile phase in supercritical fluid chromatography (SFC) allows higher flow rates and lower pressure drops than is possible in traditional HPLC. In addition, SFC requires less organic, or aqueous-organic, solvent than LC (important in preparative-scale chromatography) and provides an alternative, normal-phase retention mechanism. But fluids that are commonly used as the main mobile-phase component in SFC, such as CO2, are relatively nonpolar. As a result, SFC is commonly believed to only be applicable to nonpolar and relatively low-polarity compounds. Here we build upon recent work with SFC of polar and ionic compounds and peptides, and we compare the LC/MS and SFC/MS of a diverse library of druglike compounds. A total of 75.0% of the library compounds were eluted and detected by SFC/MS, while 79.4% were eluted and detected by LC/MS. Some samples provided strong peaks that appeared to be related to the purported compound contained in the sample. When these were added to the "hits", the numbers rose to 86.7 and 89.9%, respectively. A total of 3.7% of the samples were observed by SFC/MS, but not by LC/MS, and 8.1% of the samples were observed by LC/MS, but not by SFC/MS. The only compound class that appeared to be consistently detected in LC/MS, but not in SFC/MS under our conditions, consisted of compounds containing a phosphate, a phosphonate, or a bisphosphonate. The SFC/MS method was at least as durable, reliable, and user-friendly as the LC/MS method. The APCI source required less cleaning during the SFC/MS separations than it did during LC/MS.

We report results for the virtual photon asymmetry A{sub 1} on the nucleon from new Jefferson Lab measurements. The experiment, which used the CEBAF Large Acceptance Spectrometer and longitudinally polarized proton ({sup 15}NH{sub 3}) and deuteron ({sup 15}ND{sub 3}) targets, collected data with a longitudinally polarized electron beam at energies between 1.6 GeV and 5.7 GeV. In the present paper, we concentrate on our results for A{sub 1}(x,Q{sup 2}) and the related ratio g{sub 1}/F{sub 1}(x,Q{sup 2}) in the resonance and the deep inelastic regions for our lowest and highest beam energies, covering a range in momentum transfer Q{sup 2} from 0.05 to 5.0 GeV{sup 2} and in final-state invariant mass W up to about 3 GeV. Our data show detailed structure in the resonance region, which leads to a strong Q{sup 2}--dependence of A{sub 1}(x,Q{sup 2}) for W below 2 GeV. At higher W, a smooth approach to the scaling limit, established by earlier experiments, can be seen, but A{sub 1}(x,Q{sup 2}) is not strictly Q{sup 2}--independent. We add significantly to the world data set at high x, up to x = 0.6. Our data exceed the SU(6)-symmetric quark model expectation for both the proton and the deuteron whilemore » being consistent with a negative d-quark polarization up to our highest x. This data set should improve next-to-leading order (NLO) pQCD fits of the parton polarization distributions.« less

Exclusive ω electroproduction off the proton was measured at the highest possible four-momentum transfer with the (close to) 6 GeV beam now available at CEBAF. Cross sections are presented, together with an analysis of the ω spin density matrix elements. Indications are that π0 exchange in the t-channel (or rather the exchange of the corresponding saturating Regge trajectory) seems to dominate the process γ*p→ωp, even for photon virtuality Q2 as large as 5 GeV2. Contributions of the handbag type, related to Generalized Parton Distributions in the nucleon, are therefore difficult to extract from this particular process.

The stability of approximately 7200 compounds stored as 20-mM DMSO solutions under ambient conditions was monitored for 1 year. Compound integrity was measured by flow injection analysis using positive and negative electrospray ionization mass spectrometry. Each sample was assessed at the beginning of the study, after 12 months of storage, and at a randomized time point between the initial and final time points of the study. The relationship between length of storage and the probability of observing the compound was described by a repeated-measures logistic regression model. The probability of observing the compound was 92% after 3 months of storage at room temperature, 83% after 6 months, and 52% after 1 year in DMSO. An acceptable limit for compound loss and corresponding maximum storage time for samples in DMSO can be determined based on these results.

The landscape of today's telecommunications portrays an amazing patchwork of heterogeneous networks, with very few and complex bridges between them. In this context, IP technology has emerged as a natural means of initiating network convergence and the "All-IP" paradigm has become the implicit assumption for most studies on the next generation architecture design. However, the real added value of such networks from the user's point of view will lie in offering seamless and transparent services through any kind of network. This can only be achieved with a global solution for mobility management and some believe it to be Mobile IP. The purpose of this paper is to describe how the EURESCOM project P1013 FIT-MIP has evaluated the use of Mobile IP acting as a mobility management protocol federating various access network technologies such as PSTN, Wireless LAN or General Packet Radio System. The use of Mobile IP as the enabler for inter-access technology handoffs will be the first step towards providing always-on access to IP applications (e.g., VoIP, VPN, mobile Internet).

In the pharmaceutical industry, there is a tremendous need for qualitative and quantitative analysis of target analytes such as peptides, proteins, drugs, metabolites, biomarkers, impurities, and degradation products in various mixtures including synthetic reactions, in vitro cultures, biological fluids, drug substances, finished products, and many others. To provide adequate specificity for analysis in these complex mixtures, multidimensional analytical techniques are required. Mass spectrometry plays a central role in many of these multidimensional approaches to mixture analysis because it provides an unparalleled combination of sensitivity and specificity that is useful for both molecular identification and quantitative applications. Recent innovations in mass spectrometry and industrial implementation of these advances have transformed many aspects of pharmaceutical research and development. Data that were previously unattainable, or were not collected due to exorbitant cost or time constraints, can now be obtained using mass spectrometry-based technologies. The impact of these innovations has been most dramatically felt in early stages of discovery, as more data are available to make critical decisions, such as selecting compounds for advancement to costly preclinical and clinical trials. New MS technologies have also accelerated the progression of drug candidates through development and toward regulatory approval. Here, five major categories of pharmaceutical applications of mass spectrometry are reviewed. They are new chemical entity characterization, biomacromolecule characterization, bioanalytical quantitation, metabolite identification, and impurity and degradation product identification. A brief historical perspective and evolution of technologies for each application area are presented. Those discussions are followed with a description of the current strategies for implementation of the tremendous capabilities of the state-of-the-art approaches, along with representative applications. In addition, emerging technologies for each application area are presented to indicate the future directions of instrumentation for mixture analysis in the pharmaceutical industry.

An effort to identify novel inhibitors of peptidoglycan synthesis with antibacterial activity resulted in the discovery of a series of biaryl urea-based antibacterial agents through isolation of a by-product from a mixture-based combinatorial library of semi-carbazones and subsequent parallel synthesis efforts. The compounds were shown to possess broad spectrum antibacterial activity against gram-positive drug resistant pathogens, and showed apparent specificity for disruption of the bacterial cell wall biosynthesis pathway.

Introduction La crise renale sclerodermique (CRS) est une complication rare et grave de la sclerodermie. Nous rapportons 11 cas de CRS au sein d’une cohorte de 110 sclerodermies suivies dans un service universitaire. Patients et methodes Il s’agit d’une etude retrospective de 2006 a 2016 portant sur les patients presentant une CRS. L’objectif principal etait de decrire la population avec CRS : presentation clinique et biologique, prise de corticotherapie, participation au programme d’education therapeutique, survie globale, survie renale et recours eventuel a la transplantation. Les patients presentant les criteres diagnostiques de CRS ont ete selectionnes a partir d’une cohorte de patients sclerodermiques prevalents suivis dans un centre de competence. Resultats Onze patients ont presente une CRS. Il s’agissait de 9 femmes et 2 hommes d’âge median 62 ans. Neuf patients avaient une forme diffuse. La duree mediane d’evolution entre le premier signe hors Raynaud et la CRS etait de 11,4 ans. Au moment de la CRS, 2 patients avaient une fibrose pulmonaire, 3 avaient eu au moins une ulceration digitale, 3 patients avaient un Rodnan > 30 et un patient presentait une HTAP. La duree moyenne d’evolution entre le diagnostic de SSc et la CRS etait de 2,98 ans. Les CRS etaient inaugurales chez 45 % des patients (n = 5). Tous les patients avaient des anticorps antinucleaires (4 antinucleolaires, 3 anti-scl70, 2 PmScl et 2 anti-SSA). Les anti-ARN polymerase III etaient positifs chez une seule patiente (sur 4 recherches). Huit patients avaient recu des corticoides avant la CRS dont 6 a plus de 15 mg/j. Tous les patients etaient hypertendus au diagnostic de CRS, les œdemes etaient presents chez 4 patients, 7 presentaient une alteration de l’etat general. La creatininemie mediane etait de 418 μmol/L, les taux medians d’hemoglobine et de plaquettes etaient respectivement de 8,9 g/dL et 97 000/mm3. Dix patients avaient les LDH elevees et 9 avaient des schizocytes. Tous les patients ont recu un IEC. Le recours a la dialyse etait necessaire chez 7 patients. La duree mediane de dialyse etait de 3,5 mois. Une patiente etait encore dependante de l’hemodialyse a la fin du suivi. Un patient a ete greffe. Aucun patient n’a recupere une fonction renale normale. Une patiente a ete mise sous Bosentan dans le cadre d’un protocole. Deux patients ont eu des echanges plasmatiques par meconnaissance du diagnostic. A la fin du suivi, 5 patients sont decedes (a 1,91 ans du diagnostic de CRS). Les causes de deces etaient : 2 cancers, 2 defaillances cardiaques, une radionecrose postradique d’un meningiome. Une seule patiente avait beneficie du programme d’education therapeutique avant l’apparition de la crise mais n’etait pas venue a la seance concernant la CRS. Discussion Notre serie de patients avec CRS est interessante car elle correspond a l’activite d’un centre de competence sur une duree de 10 ans. Les resultats sont comparables aux donnees de la litterature [1] , [2] en ce qui concerne la prevalence, la duree d’evolution, la presentation clinique et biologique des CRS. La corticotherapie est retrouvee comme facteur favorisant dans 75 % des cas. Tous les patients ont recu le traitement de reference. Par contre, dans notre serie, la CRS est inaugurale dans presque la moitie des cas. Dans notre serie, aucun patient n’est decede de la CRS, par contre, le suivi montre que les deces sont lies a la presence d’un cancer ou secondaire a une defaillance cardiaque, temoignant pour cette derniere de presentations severes de la sclerodermie. Cependant, cette etude est retrospective, avec neanmoins peu de donnees manquantes, la recherche d’anti-ARN polymerase III n’a pu etre realisee que dans les cas les plus recents. L’etude des facteurs pronostiques de morbidite au sein de la cohorte sera realisee. Conclusion Les CRS surviennent chez les patients presentant une forme severe de SSc. Si la mortalite n’est plus un enjeu, les CRS ont une morbidite importante malgre l’utilisation des IEC, en particulier en terme de maladie renale. Les formes inaugurales de CRS sont difficiles a prevenir, d’ou l’importance de la formation des medecins a cette pathologie, et la prise en charge collaborative, en particulier avec les reanimateurs. La mise en place de courriers avertissant patients et medecins des facteurs de risques evitables de CRS, et les programmes d’education therapeutique sont des moyens d’optimiser la prevention des CRS chez un patient connu pour avoir une SSc.

A randomized double-blind controlled trial was conducted to determine the efficacy of passive immunotherapy in the treatment of symptomatic human immunodeficiency virus (HIV) infection. This trial included 86 symptomatic patients randomized to receive plasma rich in anti-HIV-1 antibody or standard seronegative plasma. Each patient in both groups received a 300-ml infusion every 14 days over a 1-year period, and every 28 days thereafter, in addition to zidovudine and other conventional prophylactic treatments. Plasma donors were selected among symptomless seropositive individuals with a CD4 lymphocyte count > or = 400 x 10(6) cells per liter, a negative p24 antigen assay, and a high concentration of anti-p24 antibody. The plasmas were heat-inactivated before infusion. During the study period (day 28-day 365) scheduled by the protocol, clinical benefit from passive immunotherapy was observed in delaying the appearance of the first AIDS-defining event (P < 0.009) and reducing the cumulative incidence of such events, which was estimated 3-fold higher in the control group compared to the treatment group. Seven deaths occurred in the treatment group vs. 11 in the control group (P = 0.27). A total of 47 patients died or exhibited new AIDS-defining events, 18 in the treatment group and 29 in the control group (P = 0.009). No clinical benefit was observed after the 1-year period with infusions performed every 4 weeks. These results indicate a favorable effect of passive immunotherapy on the evolution of advanced AIDS.

Background : Recent trials have shown the potential benefits of ritonavir-boosted protease inhibitor (PI/r) monotherapy. As this alternative strategy has recently been included in European HIV treatment guidelines, its effectiveness needs to be assessed in routine practice. Methods : From 1st January to 31 December 2011, we identified all patients receiving a current PI/r monotherapy at a university-based hospital setting using the Diamm database system. Antiretroviral-naive patients who directly initiated PI/r monotherapy were excluded. Patients who continued PI/r monotherapy after ending participation in a clinical trial were also included. We performed a retrospective, descriptive analysis of demographic, clinical and therapeutic characteristics of these patients. For biological variables, the last available value in 2011 was retained. Results : In 2011, among 3140 antiretroviral-treated patients in our department, 107 (3.4%) received PI/r monotherapy (lopinavir/r n=58, darunavir/r n= 49). Of them, 30 (28%) started during 2011 and 31 (29%) continued after a prior trial. Two patients switched to DRV/r due to intolerance. Eighty-eight percent were male and median age at initiation was 45 years. The median time from starting multitherapy and switching to monotherapy was 30 months (range 2-117). At PI/r monotherapy initiation, median CD4 count was 567 cells/mm 3 and HIV RNA was below 50 copies/mL in 90% of patients. The median duration under PI/r monotherapy was 25.4 months (range 0.5-93). At the end of follow-up, median CD4 count was 643 cells/mm 3 and HIV RNA was below 50 copies/mL in 89% of cases. During 2011, 11 patients discontinued PI/r monotherapy, of whom 8 presented viral rebound. Only one patient exhibited major protease mutations. All these 8 patients achieved an undetectable viral load 3 months after therapeutic intensification. Conclusion : This descriptive analysis shows that PI/r monotherapy in routine practice could be considered as an alternative and successful maintenance strategy, especially among patients who achieved an undetectable viral load while undergoing prior multitherapy (Published: 11 November 2012) Citation: Abstracts of the Eleventh International Congress on Drug Therapy in HIV Infection Fonquernie L et al. Journal of the International AIDS Society 2012, 15 (Suppl 4):18255 http://www.jiasociety.org/index.php/jias/article/view/18255 | http://dx.doi.org/10.7448/IAS.15.6.18255

Animal development depends on cell communication by signals. We have investigated the role of signals and of signal transduction in the development of the marine hydroid Hydractinia echinata. The larvae undergo metamorphosis in response to a chemical signal provided by environmental bacteria. Metamorphosis can be induced by a variety of different compounds interfering with biochemical signal transduction pathways. Sectioned posterior parts cannot be induced by most compounds known to induce whole larvae to metamorphose. We identified a novel peptide, pGlu-Gln-Pro-Gly-Leu-TrpNH2 ("metamorphosin A"), which induces isolated posterior parts to undergo metamorphosis and hence reactivates pattern formation, cell proliferation, cell differentiation, and morphogenesis. We suggest this peptide to be part of an internal signaling system involved in control of metamorphosis.

[M + H + 16]+ ions were observed in the electrospray ionization mass spectra of several synthetic and naturally occurring peptides. Initial results have shown that the appearance of the modification is dependent on the field strength at the electrospray needle and the flow rate of the solution passing through the capillary. Mass spectrometric experiments on peptides showing the + 16 Da modification attributed the change to the selective oxidation of either a methionyl, tryptophanyl, or tyrosyl residue present in the peptide. These results were further confirmed by tandem mass spectrometry experiments on peptides with a methionyl residue at either the N- or C-terminus, or within the peptide chain. This effect can occur under normal operating conditions and therefore care must be taken in the analysis of samples containing these oxidizable residues. Conversely, the selectivity of the oxidative process may be used to enhance the information obtained from the mass spectrometric analysis. For example, we show results for the analysis of a tryptic digest of the protein myoglobin where the occurrence of the [M + H + 16]+ ion is used, along with the molecular weight data, to correctly identify the trypic fragment.

Developments in mass spectrometry instrumentation over the past three years are reviewed. The subject is characterized by an enormous diversity of designs, a high degree of competition between different laboratories working with either different or similar techniques and by extremely rapid progress in improving analytical performance. Instruments can be grouped into genealogical charts based on their physical and conceptual interrelationships. This is illustrated using mass analyzers of different types. The time course of development of particular instrumental concepts is illustrated in terms of the s-curves typical of cell growth. Examples are given of instruments which are at the exponential, linear and mature growth stages. The prime examples used are respectively: (i) hybrid instruments designed to study reactive collisions of ions with surfaces: (ii) the Paul ion trap; and (iii) the triple quadrupole mass spectrometer. In the area of ion/surface collisions, reactive collisions such as hydrogen radical abstraction from the surface by the impinging ion are studied. They are shown to depend upon the chemical nature of the surface through the use of experiments which utilize self-assembled monolayers as surfaces. The internal energy deposited during surface-induced dissociation upon collision with different surfaces in a BEEQ instrument is also discussed. Attention is also given to a second area of emerging instrumentation, namely technology which allows mass spectrometers to be used for on-line monitoring of fluid streams. A summary of recent improvements in the performance of the rapidly developing quadrupole ion trap instrument illustrates this stage of instrument development. Improvements in resolution and mass range and their application to the characterization of biomolecules are described. The interaction of theory with experiment is illustrated through the role of simulations of ion motion in the ion trap. It is emphasized that mature instruments play a dominant role in most work using mass spectrometers. This is illustrated with recent results on the chemistry of C+.60 including the formation of covalent adducts with aromatic compounds. Quantitative analysis of methylated nucleosides and structural studies of the anti-cancer drug taxol are also discussed. A compendium of mass spectrometers constructed over the past three years is provided. This includes a variety of hybrid instruments, combinations of sector mass spectrometers with traps, instruments designed to study collision dynamics, and many more.

Heavy target gases (neon, argon, krypton or xenon), when added in small amounts to the helium buffer gas in the quadruple ion trap, improve both the trapping efficiency of cesium iodide cluster ions of high mass-to-charge ratio and the internal energy deposition during collision-induced dussociation experiments.

The combination of capillary supercritical fluid chromatography (SFC) and ion trap mass spectrometry using an external, differentially-pumped ion source is described. This was accomplished using a capillary SFC instrument with direct, on-column injection, and a custom-built, direct-introduction interface to a quadrupole mass filter/ion trap (Q/trap). The hybrid mass spectrometer was equipped with a standard EI/CI ion source and operated with conventional ion trap detector (ITD) electrodes and electronics

The fullerenes C 60 and C 70 can be ionized by desorption from a liquid matrix upon bombardment by Cs + ions of 7 keV kinetic energy. The resulting radical cations, when activated in the ion trap by collisions with Xe target, in the presence of helium, undergo extensive dissociation by loss of multiple C 2 units. Large internal energies are deposited into these molecular ions and the dissociation efficiency is in excess of 60%

A quadrupole ion-trap mass spectrometer (ITMS) has been used to examine internal energy disposition and fragmentation pathways of ionized pyrene and anthracene. Through multiple collisional activation steps, large amounts of energy (tens of electrovolts) can be deposited and multiple-stage (MS{sup n}) dissociation reactions such as C{sub 16}H{sub 10}{sup {sm_bullet}+}{r_arrow}C{sub 16}H{sub 9}{sup +}{r_arrow}C{sub 16}H{sub 8}{sup {sm_bullet}+}{r_arrow}C{sub 14}H{sub 6}{sup {sm_bullet}+}{r_arrow}C{sub 12}H{sub 4}{sup {sm_bullet}+}{r_arrow}C{sub 8}H{sub 2}{sup {sm_bullet}+}{r_arrow}C{sub 3}H{sub 2}{sub {sm_bullet}+} are observed. This particular reaction sequence requires approximately 29 eV, as estimated from the energy requirements for the individual dissociation reactions. While each individual reaction has an activation energy

A new tandem mass spectrometer has been constructed by interfacing a Paul ion trap mass spectrometer to a quadrupole mass filter. Ions generated in an EI—CI source are mass-selected using the quadrupole and injected in 50–100 ms pulses into the ion trap at injection energies which range from nominally zero to 150 eV. Helium gas at a pressure of 1 mTorr is used to dampen the ion motion and thus trap the injected ions. Stored ions, as well as their dissociation and ion/molecule reaction products, are detected using the mass-selective instability scan mode of the ion trap. Ions generated from perfluorotributylamine, polycyclic aromatic hydrocarbons, xenon and tungsten hexacarbonyl all show efficient trapping at injection energies ranging from 10 to 110 eV. As the injection energy is raised, the internal energy deposited in the projectile increases, as demonstrated by displaying fragment ion abundances versus injection energy in the form of breakdown curves. Pyrene and other PAH ions undergo extensive fragmentation at injection energies ⩾ 100 eV to give spectra which resemble those recorded using surface-induced dissociation (SID). These and other data suggest that ions injected with sufficient kinetic energies collide with the trap surface during injection. Gas phase ion/molecule reactions also occur and lead to formation of [M + 17]+ from PAH molecular ions and abundant dinuclear ions from tungsten hexacarbonyl. The new instrument is evaluated and compared with other tandem mass spectrometers.

The helicity amplitudes of the electroexcitation of the Roper resonance are extracted for $1.7l{Q}^{2}l4.5\phantom{\rule{0.3em}{0ex}}{\mathrm{GeV}}^{2}$ from recent high precision JLab-CLAS cross section and longitudinally polarized beam asymmetry data for ${\ensuremath{\pi}}^{+}$ electroproduction on protons at $W=1.15\ensuremath{-}1.69$ GeV. The analysis is made using two approaches, dispersion relations and a unitary isobar model, which give consistent ${Q}^{2}$ behavior of the helicity amplitudes for the ${\ensuremath{\gamma}}^{*}p\ensuremath{\rightarrow}$N(1440)P${}_{11}$ transition. It is found that the transverse helicity amplitude ${A}_{1/2}$, which is large and negative at ${Q}^{2}=0$, becomes large and positive at ${Q}^{2}\ensuremath{\simeq}2\phantom{\rule{0.3em}{0ex}}{\mathrm{GeV}}^{2}$, and then drops slowly with ${Q}^{2}$. The longitudinal helicity amplitude ${S}_{1/2}$, which was previously found from CLAS $\stackrel{\ensuremath{\rightarrow}}{e}p\ensuremath{\rightarrow}\mathit{ep}{\ensuremath{\pi}}^{0},\mathit{en}{\ensuremath{\pi}}^{+}$ data to be large and positive at ${Q}^{2}=0.4,0.65\phantom{\rule{0.3em}{0ex}}{\mathrm{GeV}}^{2}$, drops with ${Q}^{2}$. Available model predictions for ${\ensuremath{\gamma}}^{*}p\ensuremath{\rightarrow}$N(1440)P${}_{11}$ allow us to conclude that these results provide strong evidence in favor of N(1440)P${}_{11}$ as a first radial excitation of the $3q$ ground state. The results of the present paper also confirm the conclusion of our previous analysis for ${Q}^{2}l1$ GeV${}^{2}$ that the presentation of N(1440)P${}_{11}$ as a q$^{3}\mathrm{G}$ hybrid state is ruled out.

Electroproduction of exclusive \ensuremath{\phi} vector mesons has been studied with the CLAS detector in the kinematic range $1.4\ensuremath{\leqslant}{Q}^{2}\ensuremath{\leqslant}3.8$ GeV${}^{2},0.0\ensuremath{\leqslant}{t}^{'}\ensuremath{\leqslant}3.6$ GeV${}^{2}$, and $2.0\ensuremath{\leqslant}W\ensuremath{\leqslant}3.0$ GeV. The scaling exponent for the total cross section as $1/({Q}^{2}+{M}_{\ensuremath{\phi}}^{2}){}^{n}$ was determined to be $n=2.49\ifmmode\pm\else\textpm\fi{}0.33$. The slope of the four-momentum transfer ${t}^{'}$ distribution is ${b}_{\ensuremath{\phi}}=0.98\ifmmode\pm\else\textpm\fi{}0.17$ GeV${}^{\ensuremath{-}2}$. Under the assumption of $s$-channel helicity conservation, we determine the ratio of longitudinal to transverse cross sections to be $R=0.86\ifmmode\pm\else\textpm\fi{}0.24$. A two-gluon exchange model is able to reproduce the main features of the data.

The (W,Q{sup 2}) dependence of the ratio of inclusive electron scattering cross sections for {sup 15}N/{sup 12}C was determined in the kinematic ranges 0.8