Modélisation et cartographie des opérations de transport

Ce document a pour but de décrire les processus de prise d’appels et de formation des routes de la compagnie Med Express. L’étude commence par effectuer la cartographie des flux des opérations ainsi qu’une analyse sur la construction des routes. L’analyse des routes construites par Med Express a démontré qu’il y avait un haut taux de retard. En utilisant un algorithme, la moyenne d’appels par route est restée semblable, mais sans aucun retard. En traitant les appels comme préprogrammés, le nombre moyen d’appels par route a augmenté tout en diminuant la distance totale parcourue. Ces résultats nous ont permis d’affirmer que la séparation myope des appels entre les répartiteurs diminue l’efficacité globale de la flotte. De plus, le fait de connaitre la demande à l’avance est un avantage. Finalement, un léger changement dans les heures de cueillettes permet de grandes améliorations globales quant à la distance parcourue et au nombre d’appels par route

La créativité en classe : un exemple dans l'enseignement des arts

Québec Université Laval, Bibliothèque 201

Conservation of Pathogenic TCR Homology across Class II Restrictions in Anti-Ribonucleoprotein Autoimmunity: Extended Efficacy of T Cell Vaccine Therapy

T cells have been shown to mediate aspects of anti-RNP autoimmunity, and are a potential target of therapy in lupus and related diseases. In this study, we assessed the relevance of a conserved class of anti-RNP T cells to autoimmune disease expression and therapy. Our data show that anti-RNP T cell selection induced a limited set of homologous CDR3 motifs at high frequency. Homologous CDR3 motifs have been reported in other autoimmune diseases. Vaccination with irradiated anti-RNP (but not anti-Tetanus Toxoid) CD4+ cells induced remission of anti-RNP-associated nephritis in at least 80% of treated mice, even with donor/recipient MHC Class II mismatch, and in both induced and spontaneous autoimmunity. Vaccine responder sera inhibited anti-70k T cell proliferation and bound hybridomas expressing the conserved CDR3 motifs. Our data indicate that a limited set of TCR CDR3 motifs may be important for the pathogenesis of anti-RNP lupus and other autoimmune diseases. The ability to target a consistent set of pathogenic T cells between individuals and across Class II restrictions may allow for the more practical development of a standardized anti-RNP T cell vaccine preparation useful for multiple patients

Clinical and Immunologic Manifestations of Mixed Connective Tissue Disease in a Miami Population Compared to a Midwestern US Caucasian Population

OBJECTIVE: A cross-sectional study of mixed connective tissue disease (MCTD) was performed to determine if there were identifiable differences in the clinical expression of MCTD associated with race or ethnicity. METHODS: Miami, Florida, and Midwestern US (Missouri) Caucasian MCTD cohorts were studied. Clinical and laboratory features of the 2 MCTD cohorts were compared. A concurrently collected cohort of Sm-positive patients with systemic lupus erythematosus (SLE) was studied as a control. Disease activity and severity and functional status were measured. CD4+CD25(high)-expressing T-regulatory cells were enumerated and serum soluble L selectin was measured as biomarkers of disease activity. RESULTS: The Miami and Missouri Caucasian MCTD groups, while differing from the SLE group, were largely similar; however, gastroesophageal reflux, sclerodactyly, and malar rash were significantly more frequent in the Missouri MCTD group and alopecia was more frequent in the Miami MCTD group. Significant clinical and laboratory differences were found between the Miami MCTD and Miami SLE groups despite similar disease duration, activity, severity and functional status. Raynaud's phenomenon (RP), hand swelling, synovitis, myositis, and sclerodactyly were all significantly more common in RNP-positive MCTD versus Sm-positive SLE subjects. CONCLUSION: Ethnic differences were observed in the frequency of end-organ involvement in the Miami MCTD versus the Missouri Caucasian MCTD groups. Clinical and laboratory features of all MCTD groups were clearly different from the SLE group, despite similar disease activity, disease severity, and functional status. Disease activity measures appeared to behave similarly as valid measures of disease activity in SLE and MCTD

FRI0261 B cell stimulating cytokines baff, IL-21 and IL-33 mrna expression are elevated coordinately in active rnp autoantibody+ sle

Background We examined a cohort of 79 consecutive patients classified as anti-ribonuclear protein (anti-RNP)+ systemic lupus erythematosus (SLE). All patients provided RNA samples obtained after providing informed consent. There were 73 female and 6 male subjects. Disease duration ranged from 0 to 453 months with a median of 37.5 months. SLE Disease Activity Index (SLEDAI) ranged from 0 to 31 with a median of 6. The goal of this study was to characterize gene expression profiles in active and inactive RNP autoantibody+ SLE versus healthy blood donors. Methods Gene expression profiling was performed using Affymetrix microarrays on 79 patients and 30 healthy blood donors. mRNA from the 109 samples passed quality control and were analyzed using Affymetrix U133 Plus 2.0 expression arrays to determine gene expression, and data were compared after normalization using Robust Multichip Average algorithm. Statistical analyses were performed using two-sample t-test or univariate regression analysis. Results BAFF, IL-21, IL-33, and CXCL13 mRNA expression was significantly higher in patients versus healthy controls (p<2E-8) while ICOS and CXCR5 were lower in patients (p<3.7E-18). There were strong correlations between expression of these genes, especially in patients with more active disease as defined by SLEDAI of 6 or greater. BAFF, IL-21, IL-33, and CXCL13 were high in patients with active disease. In addition, several of these were coordinately regulated. We found correlation for BAFF vs ICOS (p<0.02); BAFF vs CXCR5 (p<0.02); IL-21 vs ICOS (p<0.0001); IL-21 vs CXCR5 (p<0.0001) and IL-33 vs ICOS (p<0.02). Conclusions There was elevation of mRNA expression for the B cell stimulatory cytokines BAFF, IL-21 and IL-33 in active RNP+ SLE supporting the concept that these are potentially important therapeutic targets for treatment of SLE in the presence of autoantibodies. In addition, the observed differences of mRNA expression of factors influencing B cell migration and trafficking, ICOS and CXCL13-CXCR5, and the apparent coordinate change of these with other B cell stimulator cytokines (BAFF, IL-21 and IL-33) in active SLE suggests that these may also be of importance in disease pathogenesis. Disclosure of Interest: E. Greidinger Consultant for: Eli Lilly & Company, J. Pignac-Kobinger: None Declared, A. Garza Romero: None Declared, N. Perumal Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, V. Kondragunta Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Company, R. Hoffman Shareholder of: Eli Lilly & Company, Employee of: Eli Lilly & Compan