Spondylarthropathies (including psoriatic arthritis): 244. Validity of Colour Doppler and Spectral Doppler Ultrasound of Sacroilicac Joints Againts Physical Examination as Gold Standard

Background: Sacroiliac joints (SJ) involvement is a distinctive and charasteristic feature of Spondyloarthritis (SpA) and x-ray is the test routinely used to make a diagnosis. However, x-ray reveals late structural damage but cannot detect active inflammation. The objective of this study was to assess the validity of Doppler ultrasound in SJ. Methods: Prospective blinded and controlled study of SJ, in which three populations were compared. We studied 106 consecutive cases, who were divided into three groups: a) 53 patients diagnosed with SpA who had inflammatory lumbar and gluteal pain assessed by a rheumatologist; b) 26 patients diagnosed with SpA who didn't have SJ tenderness and had normal physical examination; c) control group of 27 subjects (healthy subjetcs or with mechanical lumbar pain). All patients included that were diagnosed with SpA met almost the European Spondyloarthropathy Study Group (ESSG) classification criteria. Physical examination of the SJ included: sacral sulcus tenderness, iliac gapping, iliac compression, midline sacral thrust test, Gaenslen's test, and Patrick s test were used as gold standard. Both SJ were examined with Doppler ultrasound (General Electric Logiq 9, Wauwatosa WI, USA) fitted with a 9-14 Mhz lineal probe. The ultrasonographer was blinded to clinical data. Doppler in SJ was assessed as positive when both Doppler colour and resistance index (RI) < 0.75 within the SJ area were present. Statistical analysis was performed estimating sensitivity and specificity against gold standard. The Kappa correlation coefficient was used for reliability study. Results: 106 cases (53 female, 55 male; mean age 36 10 years) were studied. There were no statistical differences between groups related to age or sex. Physical examination of SJ was positive in 38 patients (59 sacroiliac joints). US detected Doppler signal within SJ in 37 patients (58 SJ): 33 of them were symptomatic SpA (52 SJ), one of them were asymptomatic SpA (1 SJ) and one was a healthy control (1 SJ). The accuracy of US when compared to clinical data as gold standard at subject level in the overall group was: sensitivity of 68.6% and specificity of 85.7%, positive predictive value of 70.5% and negative predictive value of 84.5%. A positive likelihood ratio of 4.8, a negative likelihood ratio of 0.36 and a kappa coefficient of 0.55 were achieved. Conclusions: Doppler US of SJ seems to be a valid method to detect active SJ inflammation. Disclosure statement: The authors have declared no conflicts of interes

Rheumatoid arthritis - clinical aspects: 134. Predictors of Joint Damage in South Africans with Rheumatoid Arthritis

Background: Rheumatoid arthritis (RA) causes progressive joint damage and functional disability. Studies on factors affecting joint damage as clinical outcome are lacking in Africa. The aim of the present study was to identify predictors of joint damage in adult South Africans with established RA. Methods: A cross-sectional study of 100 black patients with RA of >5 years were assessed for joint damage using a validated clinical method, the RA articular damage (RAAD) score. Potential predictors of joint damage that were documented included socio-demographics, smoking, body mass index (BMI), disease duration, delay in disease modifying antirheumatic drug (DMARD) initiation, global disease activity as measured by the disease activity score (DAS28), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and autoantibody status. The predictive value of variables was assessed by univariate and stepwise multivariate regression analyses. A p value <0.05 was considered significant. Results: The mean (SD) age was 56 (9.8) years, disease duration 17.5 (8.5) years, educational level 7.5 (3.5) years and DMARD lag was 9 (8.8) years. Female to male ratio was 10:1. The mean (SD) DAS28 was 4.9 (1.5) and total RAAD score was 28.3 (12.8). The mean (SD) BMI was 27.2 kg/m2 (6.2) and 93% of patients were rheumatoid factor (RF) positive. More than 90% of patients received between 2 to 3 DMARDs. Significant univariate predictors of a poor RAAD score were increasing age (p = 0.001), lower education level (p = 0.019), longer disease duration (p < 0.001), longer DMARD lag (p = 0.014), lower BMI (p = 0.025), high RF titre (p < 0.001) and high ESR (p = 0.008). The multivariate regression analysis showed that the only independent significant predictors of a higher mean RAAD score were older age at disease onset (p = 0.04), disease duration (p < 0.001) and RF titre (p < 0.001). There was also a negative association between BMI and the mean total RAAD score (p = 0.049). Conclusions: Patients with longstanding established RA have more severe irreversible joint damage as measured by the clinical RAAD score, contrary to other studies in Africa. This is largely reflected by a delay in the initiation of early effective treatment. Independent of disease duration, older age at disease onset and a higher RF titre are strongly associated with more joint damage. The inverse association between BMI and articular damage in RA has been observed in several studies using radiographic damage scores. The mechanisms underlying this paradoxical association are still widely unknown but adipokines have recently been suggested to play a role. Disclosure statement: C.I. has received a research grant from the Connective Tissue Diseases Research Fund, University of the Witwatersrand. All other authors have declared no conflicts of interes

Caractérisation des coefficients d'interface en moulage sous pression de l'aluminium semi-solide

Les constructeurs automobiles travaillent depuis bon nombre d'années à réduire le poids de leurs voitures en incluant des composantes en aluminium fabriquées par moulage. Le moulage par voie semi-solide permet de réaliser des pièces de haute qualité avec une cadence de production élevée. Afin de prédire la qualité de solidification des pièces moulées, il faut résoudre des simulations numériques et ces dernières nécessitent la connaissance du coefficient d'interface de transfert de chaleur (h). Le h est une valeur qui permet de quantifier l'échange thermique qui se produit entre la pièce et le moule tout au long du processus de moulage. Ce coefficient change en fonction du temps puisque la qualité du contact entre les deux surfaces est en constante évolution en cours de moulage. Puisqu'il existe peu d'information dans la littérature en lien avec les h obtenus en utilisant du métal à l'état semi-solide et que cette information est nécessaire pour effectuer les simulations numériques, un objectif a été mis de l'avant afin de pouvoir résoudre la problématique. Cet objectif vise à obtenir une banque de données de h pour le moulage sous pression de l'aluminium A357 à l'état semi-solide pour certains paramètres de moulage, ou facteurs, considérés importants, soient : la température du moule, la vitesse du piston, la pression d'intensification, la quantité et le type de lubrifiant. La démarche scientifique utilisée pour atteindre cet objectif inclut des travaux expérimentaux, numériques et statistiques. Un plan d'expériences fractionnaire est élaboré de façon à optimiser le nombre d'essais expérimentaux de moulage sous pression devant être réalisé. Pour chacun des essais du plan d'expériences, un lopin semi-solide est fabriqué selon le procédé SEED avec la recette développée pour l'aluminium A357. Une courbe de calibration a été obtenue expérimentalement afin de connaître la température en régime stationnaire que doit atteindre le moule avant de procéder au moulage. La température du moule en régime stationnaire présente une relation linéaire avec la consigne de température donnée aux unités de régulation Regloplas. Lors de l'opération de moulage, des thermocouples placés stratégiquement à l'intérieur du moule permettent de mesurer l'évolution en température tout près de l'interface pièce/moule. Cette information est nécessaire pour procéder aux simulations numériques visant à déterminer, par le biais d'une méthode de calcul inverse, l'évolution du h qui caractérise le transfert de chaleur entre la pièce et le moule. Les simulations numériques s'effectuent à l'aide du logiciel ProCAST. Le modèle numérique et la méthodologie numérique utilisés dans le cadre du projet ont été élaborés suite à une étude de sensibilité approfondie portant sur différents facteurs. Cette étude a permis de faire ressortir quelques conclusions intéressantes : La présence du trou permettant l'insertion du thermocouple dans le moule, les valeurs choisies pour les paramètres de résolution TAU et DTMAX ainsi que la position du thermocouple (pointe du trou) sur la géométrie du modèle numérique sont quatre facteurs étudiés indépendamment qui affectent beaucoup l'évolution du h obtenue par calcul inverse à l'interface pièce/moule. Un TAU de 1 s, un DTMAX de 1 s et la position du thermocouple à 2,6 mm de l'interface sont trois conditions vérifiées qui démontrent une différence marquée au niveau des évolutions du h par rapport à celle obtenue avec le modèle optimisé (TAU = 0,001 s, DTMAX = 0,01 s et position du thermocouple à 1,6 mm de l'interface). La taille du maillage discrétisant le domaine du modèle étudié, le pas de temps choisi pour exprimer les valeurs initiales du h de 0 à 3 s ainsi que l'angle présent dans le fond du trou permettant l'insertion du thermocouple sont trois facteurs étudiés indépendamment qui affectent dans une certaine proportion l'évolution du h obtenue par calcul inverse à l'interface pièce/moule. Un maillage grossier, un pas de temps de 1 s et un angle de 45° dans le fond du trou sont trois conditions vérifiées qui démontrent une certaine différence au niveau des évolutions du h par rapport à celle obtenue avec le modèle optimisé (maillage raffiné, pas de temps de 0,1 s et angle de 67,5°). La dimension du modèle (ID ou 2D), la température initiale imposée à la partie moule du modèle étudié (identique en tout point du moule ou varie linéairement tel un gradient) et la température initiale imposée à la partie pièce du modèle étudié (586,5 ou 591,5 °C) sont trois facteurs étudiés indépendamment qui n'affectent que peu ou pas les évolutions du h obtenues par calcul inverse à l'interface pièce/moule. Cette même conclusion peut être tirée lorsque le modèle numérique pièce/moule est simplifié en imposant une condition de Dirichlet à un endroit donné du moule ou que le modèle étudié soit couplé ou découplé. Les courbes de h ont été déterminées pour chacun des essais retrouvés dans le plan d'expériences. Un modèle mathématique simple représentant l'évolution type du h a été appliqué à l'ensemble des courbes. Le modèle mathématique se divise en deux zones : évolution linéaire du h jusqu'à une valeur maximale (0 à 0,1 s) et décroissance exponentielle du h jusqu'à un régime stationnaire (0,1 à 25 s). Les valeurs de quatre variables réponses (m, a, b, ho) ont été prélevées sur chacune des courbes et incluses dans le logiciel Statgraphics pour effectuer une analyse statistique. L'analyse statistique a permis de faire ressortir un système d'équations, associé aux variables réponses, capable de reproduire le modèle mathématique décrivant l'évolution du h pour des conditions de moulage données. Ce système d'équations donne accès à une banque de données de h considérant les cinq paramètres de moulage étudiés et l'étendue des valeurs retrouvées dans le plan d'expériences. Les évolutions du h obtenues suite à l'évaluation des équations donnent tout de même de très bons résultats, mais une amélioration pourrait être faite en utilisant un modèle mathématique plus représentatif des valeurs de h obtenues suite aux calculs inverses et/ou en traitant davantage de données dans l'analyse statistique. L'analyse statistique a également mené à l'identification du paramètre de moulage dont l'influence est la plus marquée sur le h parmi ceux étudiés, soit la pression d'intensification. D'autres facteurs et interactions influencent également le h, mais de façon moins significative

Development of a versatile rheocasting technology

Since 2003, a concerted effort between Alcan Inc. (ARDC: Arvida Research and Development Centre) and the Aluminium Technology Centre (ATC) of the National Research Council of Canada is underway to develop a technology, dubbed SEED (Swirled Enthalpy Equilibration Device), to produce semi-solid aluminium feedstock. This technology, patented by Alcan Inc., is a simple process offering many advantages over thixocasting, especially for reducing the cost of feedstock. The process involves two main steps: 1) heat extraction to achieve a desired liquid/solid mixture, and 2) drainage of an excess liquid to produce a self-supporting semi-solid slug that is cast in a high pressure press. This paper reports that the SEED technology is applicable to a number of aluminium alloys and can be easily adapted to produce a wide range of slug dimensions. Furthermore, since the heat transfer plays a predominant role during the manufacture of the semi-solid slurry, its analysis is also presented.Peer reviewed: YesNRC publication: Ye

The JAK2 Inhibitor AZD1480 Potently Blocks Stat3 Signaling and Oncogenesis in Solid Tumors

SummaryPersistent activation of Stat3 is oncogenic and is prevalent in a wide variety of human cancers. Chronic cytokine stimulation is associated with Stat3 activation in some tumors, implicating cytokine receptor-associated Jak family kinases. Using Jak2 inhibitors, we demonstrate a central role of Jaks in modulating basal and cytokine-induced Stat3 activation in human solid tumor cell lines. Inhibition of Jak2 activity is associated with abrogation of Stat3 nuclear translocation and tumorigenesis. The Jak2 inhibitor AZD1480 suppresses the growth of human solid tumor xenografts harboring persistent Stat3 activity. We demonstrate the essential role of Stat3 downstream of Jaks by inhibition of tumor growth using short hairpin RNA targeting Stat3. Our data support a key role of Jak kinase activity in Stat3-dependent tumorigenesis

Tailored approaches grounded on immunogenetic features for refined prognostication in chronic lymphocytic leukemia

Chronic lymphocytic leukemia patients with differential somatic hypermutation status of the immunoglobulin heavy variable genes, namely mutated or unmutated, display fundamental clinicobiological differences. Considering this, we assessed prognosis separately within mutated and unmutated chronic lymphocytic leukemia in 3015 patients, hypothesizing that the relative significance of relevant indicators may differ between these two categories. Within Binet-A mutated chronic lymphocytic leukemia patients, besides TP53 abnormalities, trisomy 12 and stereotyped subset #2 membership were equivalently associated with the shortest time-to-first-treatment and a treatment probability at 5- and 10-years after diagnosis of 40% and 55%, respectively; the remaining cases exhibited 5-year and 10-year treatment probability of 12% and 25%, respectively. Within Binet-A unmutated chronic lymphocytic leukemia patients, besides TP53 abnormalities, del(11q) and/or SF3B1 mutations were associated with the shortest time-to-first-trearment (5- and 10-year treatment probability: 78% and 98%, respectively); in the remaining cases, males had a significantly worse prognosis than females. In conclusion, the relative weight of indicators that can accurately risk stratify early-stage chronic lymphocytic leukemia patients differs depending on the somatic hypermutation status of the immunoglobulin heavy variable genes of each patient. This finding highlights the fact that compartmentalized approaches based on immunogenetic features are necessary to refine and tailor prognostication in chronic lymphocytic leukemia

Tailored approaches grounded on immunogenetic features for refined prognostication in chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) patients with differential somatic hypermutation status of the immunoglobulin heavy variable genes, namely mutated or unmutated, display fundamental clinico-biological differences. Considering this, we assessed prognosis separately within mutated (M-CLL) and unmutated (U-CLL) CLL in 3015 patients, hypothesizing that the relative significance of relevant indicators may differ between these two categories. Within Binet A M-CLL patients, besides TP53 abnormalities, trisomy 12 and stereotyped subset #2 membership were equivalently associated with the shortest time-to first -treatment and a treatment probability at Five and ten years after diagnosis of 40% and 55%, respectively; the remaining cases exhibited 5-year and 10-year treatment probability of 12% and 25%, respectively. Within Binet A U-CLL patients, besides TP53 abnormalities, del(11q) and/or ST3B1 mutations were associated with the shortest time-to-First treatment (5- and 10-year treatment probability: 78% and 98%, respectively); in the remaining cases, males had a significantly worse prognosis than females. In conclusion, the relative weight of indicators that can accurately risk stratify early-stage CLL patients differs depending on the somatic hypermutation status of the immunoglobulin heavy variable genes of each patient. This finding highlights the fact that compartmentalized approaches based on immunogenetic features are necessary to refine and tailor prognostication in CLL

Tailored approaches grounded on immunogenetic features for refined prognostication in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) patients with differentialsomatic hypermutation status of the immunoglobulin heavy vari-able genes, namely mutated or unmutated, display fundamentalclinico-biological differences. Considering this, we assessed prognosisseparately within mutated (M-CLL) and unmutated (U-CLL) CLL in 3015patients, hypothesizing that the relative significance of relevant indica-tors may differ between these two categories. Within Binet A M-CLLpatients, besides TP53abnormalities, trisomy 12 and stereotyped subset#2 membership were equivalently associated with the shortest time-to-first-treatment and a treatment probability at five and ten years afterdiagnosis of 40% and 55%, respectively; the remaining cases exhibited5-year and 10-year treatment probability of 12% and 25%, respectively.Within Binet A U-CLL patients, besides TP53abnormalities, del(11q)and/or SF3B1mutations were associated with the shortest time-to-first-treatment (5- and 10-year treatment probability: 78% and 98%, respec-tively); in the remaining cases, males had a significantly worse prognosisthan females. In conclusion, the relative weight of indicators that canaccurately risk stratify early-stage CLL patients differs depending on thesomatic hypermutation status of the immunoglobulin heavy variablegenes of each patient. This finding highlights the fact that compartmen-talized approaches based on immunogenetic features are necessary torefine and tailor prognostication in CLL