Academic literature on the topic 'Per Jansson'

Senaste nytt i institutionens skriftserier: Kristina Jansson, Saisir l’insaisissable: les formes et les traductions du discours indirect libre dans des romans suédois et français. Acta Wexionensia nr 86/2006. Lars Olsson (red), Invandring, invandrare och etniska relationer i Sverige 1945-2005. Årsbok från forskningsmiljön AMER. Acta Wexionensia nr 79/2005. Johan Svanberg, Minnen av migrationen. Arbetskraftsinvandring från Jugoslavien till Svenska Fläktfabriken i Växjö kring 1970. Acta Wexionensia nr 80/2006. Hägerdal, Hans, Candrasangkala: The Balinese Art of Dating Events. Rapporter från Växjö universitet: Humaniora Sofia Ask, Gunilla Byrman, Solveig Hammarbäck, Maria Lindgren, Per Stille (red.), Lekt och lärt. Vänskrift till Jan Einarsson 2006. Rapporter från Växjö universitet: Humaniora, Nr 16/2006. Scripta minora Nr 47: Meike Krüger, Spuren des kollektiven Gedächtnisses im Roman Faserland von Christian Kracht. Scripta minora Nr 48: Corina Löwe, ”Eigentlich können wir uns jeden Tag entscheiden, jemand anderer zu sein” Metamorphosen von Geschlechtsanatomie und -identität, dargestellt an den Romanfiguren in Sibylle Bergs Roman Amerika. Scripta minora Nr 49: Gunilla Byrman och Jan Einarsson (red.), Två uppsatser i nordiska språk (Lovisa Alvtörn: En människas språkhistoria. I ljuset av ett vidgat lektbegrepp. Astrid Skoglund: ”Om sättet att tillhopa gå”. Jämförelse mellan två sexualvetenskapliga texter från två skilda sekel) Scripta minora Nr 50: Arvid Jurjaks, I en bländande verklighet. Om sol och hetta i Albert Camus Främlingen.

Background:Takayasu’s arteritis (TA) is a large vessel vasculitis that principally affects the aorta and its main branches. The incidence has been reported at between 1.2 – 2.3 cases per million per year, more commonly in the Asian population. The age of onset is typically between tenth and fourth decade; between 80 and 90 percent of the cases are female.The relationship between Mycobacterium Tuberculosis (mTB) and TA has long been considered; both demonstrate chronic inflammatory changes on histological examination and some granuloma formation in arterial walls. There is increasing evidence implicating mTB in the pathogenesis of TA through molecular mimicry between the mycobacterium heat shock protein -65 (mHSP-65) and the human homologue HSP -60 (hHSP-60). However, no definitive link between the two diseases has been explained.Objectives:Case presentation.Results:A 23-year-old lady was referred to our outpatient rheumatology clinic with a twelve-month history of persistently enlarged cervical lymph nodes on the left side for which she had received six months of anti-Tuberculosis medication. She had been referred to the respiratory physicians who had diagnosed presumed Tuberculous Lymphadenitis, with caseating granulomas demonstrated on biopsy, positive acid-fast bacilli smear but a negative culture. The patient had been initiated six months of anti-Tuberculosis medication; however, her lymphadenopathy showed no improvement. More recently she described a five-month history of weakness, paraesthesia and claudication symptoms in her left upper limb with episodes of dizziness and blurred vision, episodes occurring 2-3 times per day and lasting between a few minutes to a few hours.Her examination at this presentation revealed an unrecordable blood pressure in the left upper limb and 104/67mmHg in the right. There was significant tender lymphadenopathy of the left cervical lymph nodes and diminished pulses in the left upper limb. Right sided pulses were normal. The rest of her examination was normal.Investigations at presentation revealed elevated inflammatory markers with C- reactive protein (CRP) of 116mg/dL and erythrocyte sedimentation rate (ESR) of 128mm/h. Complete blood count (CBC) found her to be anaemic with a haemoglobin of 100g/L, with a mean cell volume of 71.3fl, and have elevated platelet count of 649x 109/L. Recent computerized tomography scan with contrast of the thorax demonstrated features consistent with Takayasu Arteritis. Marked left subclavian stenosis was found on magnetic resonance imaging. High dose prednisolone at 60mg once daily along with Azathioprine 2mg/kg/day was started with a follow up appointment in two weeks.Conclusion:There is increasing evidence implicating mTB in the development of TA and a few cases recognising this link have been reported. We report a case of TA in a patient recently diagnosed and treated for Tuberculous lymphadenitis who then developed symptoms of TA. There should be a low threshold for suspecting a diagnosis of Takayasu’s arteritis in patients previously or actively infected with Mycobacterium Tuberculosis. Further research exploring the relationship between mTB and TA is required.References:[1]Espinoza JL, Ai S, Matsumura I. New Insights on the Pathogenesis of Takayasu Arteritis: Revisiting the Microbial Theory. Pathogens. 2018;7(3):73.[2]Aggarwal A, Chag M, Sinha N, et al. Takayasu’s arteritis: role of Mycobacterium tuberculosis and its 65 kDa heat shock protein. International Journal of Cardiology. 1996; 55: 49–55.[3]Reshkova V, Kalinova D, Rashkov R. Takayasu’s Arteritis associated with Tuberculosis Infections. Journal of Neurology and Neuroscience. 2016; 3:114.[4]Moritz K, Jansson Hilte F, Antje Kangowski, Christian Kneitz, Emil C. Reisinger. Tuberculosis and Takayasu arteritis: case-based review Rheumatology International 2019 39:345–351[5]D Misra, A Wakhlu, V Agarwal, D Danda. Recent advances in the management of Takayasu arteritis International Journal of Rheumatic Diseases 2019; 22: 60–68Disclosure of Interests:None declared

Background:SIRENA is an Italian, prospective Registry in Spondyloarthritis (SpA) patients, naïve to conventional, targeted and biological DMARDs. Patients are diagnosed, newly or confirmed, according to ASAS criteria and classified in subjects with predominant axial(AX) or with mainly peripheral manifestations(PER).Objectives:To compare descriptively AX vs PER subgroups of patients.Methods:Demographic data, diagnostic delay and subtypes of SpA as well as clinical features and comorbidities are collected.Results:282 patients were enrolled: 101 (35.8%) AX and 181 (64.2%) PER. Baseline data are shown in Table 1. There were more obese patients in AX (21.4% AX vs 16.1% PER) and more overweight ones in PER (19.4% AX vs 23.8% PER). The % of subjects with diagnostic delay was higher in AX (65.7% vs 53.9% PER) and the delay longer (mean of 73.1 months vs 47.8). In both groups, main reason of the delay was incorrect referrals (41.5% for AX and 45.3% for PER). Noteworthy the fact that in PER, the 75.7% of patients had a newly diagnosed SpA. In PER, the most frequent SpA type was PsA (82.3%), followed by undifferentiated SpA (8.8%) and enteropathic SpA (7.5%), while in AX, 49.5% were ankylosing spondylitis, 21.8% nr-ax-SpA and only 4% PsA. The majority of PER patients reported as first symptom peripheral arthritis (80/181), psoriasis (57/181) and enthesitis while in AX referred inflammatory back pain (80/101). High percentages of comorbidities were reported: psoriasis (65.8%) and cardiometabolic diseases (34.8%) were higher in PER while depression/anxiety and GI diseases were higher in AX (Table 2). At the baseline, the mean PhGA score (0-100) was 51.5 for AX and 43.8 for PER.Conclusion:SIRENA study highlights relevant differences in AX vs PER patients, expecially in terms of diagnostic delay, clinical presentation and comorbidities.Table 1.MeanAX n=101MeanPER n=181Age (years)47.352.8Sex (female/male - %)50.5/49.547.5/52.5Weight (Kg)73.073.9BMI25.325.4Diagnostic Delay (yes - %)65.7%53.9%Time of delay (mean - months)71.347.8Newly SpA diagnosis (%)55.5%75.7%Table 2.A) First Symptom(more than 1 symptom referred)AX n=101N. PatientsPER n=181N. PatientsArthritis23122Enthesitis1654Dactylitis728Inflammatory Back Pain8034Psoriasis skin1057Psoriasis nails219Uveitis41IBD79B) Comorbidities(more than 1 comorbidity referred)% Patients% PatientsCardiometabolic20.8%34.8% -Hypertension19.8%30.9% -Dyslipidemia17.8%11.6% -Diabetes6.0%7.7% -MetS5.0%6.6%Psoriasis22.8%65.8%Gastrointestinal20.8 (16.9% CD)12.8 (4.4% CD)Depression/Anxiety11.9%2.2%Endocrine6.9%11.1%Osteoporosis3%5.5%Hepatic4% (3% NAFLD)4.4% (2.2% NAFLD)Infections3%3.9%Malignancies0%4.4%Acknowledgments:This study was sponsored by Janssen Italy.We thank the Investigators and their staff at all of the study sites.Disclosure of Interests:Rosario Foti Speakers bureau: Abbvie, BMS, ROCHE, Janssen, Celgene, Gabriella Cardinale: None declared, Luisa Costa: None declared, Franco Franceschini Consultant of: Eli-Lilly, Janssen, Pfizer, Sanofi-Genzyme, UCB Pharma, GSK, Francesco Ciccia Grant/research support from: Pfizer, Novartis, Celgene, Janssen, Consultant of: Lilly, Novartis, Pfizer, Janssen, Roche, Celgene, Speakers bureau: Pfizer, Novartis, Celgene, Janssen, Roche, Abiogen, BMS, Antonio Marchesoni Speakers bureau: Abbvie, Pfizer, UCB, Novartis, Celgene, Eli Lilly, Giuliana Guggino Grant/research support from: Pfizer, Celgene, Speakers bureau: Celgene, Sandoz, Pfizer, Maurizio Rossini Speakers bureau: AbbVie, Abiogen, Amgen, BMS, Eli-Lilly, Novartis, Pfizer, Sanofi, Sandoz and UCB, Ennio Lubrano: None declared, Mauro Galeazzi: None declared, Mariasole Chimenti: None declared, Gerolamo Bianchi Grant/research support from: Celgene, Consultant of: Amgen, Janssen, Merck Sharp & Dohme, Novartis, UCB, Speakers bureau: Abbvie, Abiogen, Alfa-Sigma, Amgen, BMS, Celgene, Chiesi, Eli Lilly, GSK, Janssen, Medac, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi Genzyme, Servier, UCB, Giuseppe Galfo: None declared, Silvia Marelli Employee of: Janssen, Ennio Favalli Speakers bureau: BMS, Eli-Lilly, MSD, UCB, Pfizer, Sanofi-Genzyme, Novartis and Abbvie

Background:Golimumab is a human monoclonal antibody directed against TNFα in its soluble and transmembrane forms. It can be used subcutaneously or intravenously and has shown efficacy for use in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS).Objectives:The aim of this study was to evaluate the efficacy, safety, and cumulative survival of golimumab in patients with RA, PsA and AS from different rheumatology centers in Argentina.Methods:We performed a longitudinal study of consecutive adults with RA (ACR/EULAR 2010 criteria), PsA (CASPAR criteria) and AS (ASAS 2009 criteria), who have started treatment with subcutaneous or intravenous golimumab according to medical indication in each center. Data was obtained by review of medical records. Sociodemographic and clinical data, musculoskeletal manifestations, comorbidities, previous treatments were recorded. In reference to golimumab treatment, start date, route of administration and concomitant treatments were identified. Disease activity was assessed using DAS28 for RA patients, DAPSA and MDA for PsA and BASDAI for AS. The presence of adverse events (AE) was recorded. If golimumab was stopped, date and cause was documented. Patients were followed up until golimumab discontinuation, loss of follow-up, or study completion (November 30, 2020). Statistical analysis: Chi2 test or Fischer exact test and T test or Mann Whitney and ANOVA or Kruskal Wallis, as appropriate. The incidence of EA was assessed in events every 100 patient/year. Kaplan-Meier curves and log Rank analysis. Cox proportional regression.Results:One hundred eighty two patients were included, 116 with a diagnosis of RA, 30 with PsA and 36 with AS. Most of them (70.9%) were female with a median (m) age of 55 years (IQR 43.8-64) and m disease duration of 7 years (IQR 4-12.7) at treatment initiation. Al least one prior biological DMARD or a small molecule was received by 63 patients (34.6%). The most frequent indication cause was conventional DMARD failure. In 94.8% of the patients Golimumab was administered subcutaneously, and in 80.8% in association with conventional DMARDs, the most frequently used was methotrexate. Total follow-up was 318.1 patients/year.Golimumab treatment showed clinical improvement in all three groups of patients. In RA patients DAS28 significantly decreased during the first 12 months of follow-up, m 5.9 (IQR 4.9-6.6) at baseline, 3.8 (IQR 2.6-4.6) at 6 months and 2.8 (IQR 2.1-3.6) at 12 months, p <0.0001. In PsA, m DAPSA-ESR value was 32.2 (IQR 24.2-47.7), 10.1 (IQR 5.8-18.3) and 11.2 (IQR 3.4-24) at baseline, 6 and 12 months, respectably (p <0.0001). In AS, m BASDAI was 6.2 (IQR 4.8-7.3), 2.8 (IQR 1.7-4.1) and 2.2 (IQR 1.1-3.2), at baseline, 6 and 12 months respectively (p <0.0001).The incidence of adverse events was 6.6 per 100 patients/year, being infections the most frequents ones. During follow-up, 50 patients (27.5%) discontinued golimumab, the most frequent cause was treatment failure (68%), followed by lack of health insurance (16%) and adverse events (10%). Golimumab persistence was 79% and 57.6% at 12 and 24 months, respectively. Treatment survival was 50.2 months (95% CI 44.4-55.9). Patients who had received prior treatment with biological DMARDs or small molecules showed lower survival (Figure 1). In the multivariate analysis, adjusting for age, sex and disease duration, those patients showed twice the risk of suspending treatment (HR 2.01, 95% CI 1.1-3.7).Figure 1.Golimumab survival according to prior b-DMARD o small molecule treatment.Conclusion:Golimumab treatment in real life patients in Argentina has shown good efficacy and safety. Drug survival was over 4 years and almost 80% were still using golimumab after one year. Prior treatment with other b-DMARDs o small molecules was associated with lower treatment survival.Disclosure of Interests:Carolina Ayelen Isnardi Speakers bureau: Bristol Myers Squibb, Janssen, Grant/research support from: Pfizer, Emma Estela Civit De Garignani Speakers bureau: Abbvie, Novartis, Agustín García Ciccarelli Speakers bureau: Janssen, Novartis, Consultant of: Novartis, Grant/research support from: Janssen, Novartis, Jimena Sanchez Alcover: None declared, Rodrigo Garcia Salinas Speakers bureau: Abbvie, AMGEN, Bristol-Myers Squibb, Eli Lilly, GSK, Janssen Cilag, Montpellier-UCB, Novartis, Roche – Genentech, Sanofi, Merck Serono., Sebastian Magri Speakers bureau: Abbvie, AMGEN, Bristol-Myers Squibb, Eli Lilly, GSK, Janssen Cilag, Montpellier-UCB, Novartis, Roche – Genentech, Sanofi, Merck Serono., Eduardo Albiero Consultant of: Janssen, Carla Gobbi Speakers bureau: Pfizer, Consultant of: Pfizer, Janssen, Edson Velozo Speakers bureau: Janssen, Novartis, Pfizer, Consultant of: Abbvie, Janssen, Novartis, Grant/research support from: Janssen, Novartis, Pfizer, Enrique Soriano Speakers bureau: AbbVie, Novartis, Bristol MS, Novartis, Eli Lilly, Genzyme, Pfizer, Amgen, and Roche, Consultant of: Novartis, AbbVie, Pfizer, Eli Lilly, Sanofi, Sandoz, Amgen., Grant/research support from: Roche, Novartis, AbbVie, Glaxo Smith Kline, BMS, Martín Brom: None declared, Johana Zacariaz Grant/research support from: Bristol Myers Squibb, Ingrid Strusberg Speakers bureau: Gema Biotech SAU, BMS, Abbvie, Consultant of: Gema Biotech SAU, Abbvie, Janssen, Grant/research support from: Abbvie, Lilly, Galápagos, Servier, GSK, Merck Serono, Marcos BARAVALLE Speakers bureau: Montepellier, Consultant of: Abbvie, Janssen, Grant/research support from: Abbvie, Lilly, Galápagos, Servier, GSK, Merck Serono, Sol Castaños Speakers bureau: Abbvie, Lilly, Galápagos, Servier, GSK, Merck Serono, Liliana Morales Speakers bureau: Lilly, Consultant of: Janssen, Grant/research support from: Abbvie, Lilly, Galápagos, Servier, GSK, Merck Serono, Sergio Paira: None declared, Romina Calvo: None declared, Alberto Ortiz: None declared, Rodolfo Perez Alamino Speakers bureau: Pfizer, Abbvie, Amgen, Bristol-Myers-Squibb, Lilly, Janssen, Novartis, Hernan Maldonado Ficco Speakers bureau: Pfizer, Abbvie, Jansen, Novartis, Bago, Bristol, Eli Lilly., Consultant of: Pfizer, Abbvie, Novartis, Jansen, Bago, Eli Lilly., Gustavo Citera Speakers bureau: Abbvie, BMS, Lilly, Jansen, Gema, Pfizer, Roche, Grant/research support from: Pfizer

Abstract Background: Multiple myeloma (MM) is an incurable and heterogeneous haematological malignancy in which immune suppression and complex biology affect the disease and its response to treatment. Several new treatments have been approved for MM in recent years providing numerous options for patients with relapsed/refractory disease. However, there is no validated method for selecting the best treatment combination for each patient, making patient management difficult. The ability to predict treatment response based on disease characteristics could improve clinically outcomes. Aim: This was a validation of a genomics-informed response prediction using computational biology modelling (CBM) in patients with relapsed/refractory MM. Methods: Input data from fluorescence in-situ hybridization (FISH), karyotype, and a MM specific next generation sequencing capture array were analysed using CBM. This was a retrospective review of patients which were treated with different combinations based on patient/physician choice. The CBM uses PubMed and other online resources to generate patient-specific protein network maps of activated and inactivated pathways. The specific drug combination for each patient was simulated and the quantitative drug effect was measured on a composite MM disease inhibition score (i.e., cell proliferation, viability, apoptosis and paraproteins). The predicted outcomes were then compared to the clinical response (≥PR or < PR per IMWG) to assess the accuracy of this CBM predictive approach. Results: 27 patients were selected for the study; 3 failed CBM due to missing inputs and in 3 clinical response was not able to be assessed, leaving 21 eligible for the analysis. The median age at presentation was 57 years (range 37-76) and 52% were male. The median prior lines of MM therapy was 5 (range 1-15). 38% were refractory to bortezomib, 62% to lenalidomide, 52% to carfilzomib, 57% to pomalidomide, and 43% to daratumumab. 81% had a prior autologous stem cell transplant. The treatments modelled included IMiD-based regimens (n = 9), PI-based regimens (n = 6), chemo-based regimens (n = 3), selinexor (n = 2), PI/IMiD combination regimens (n = 1). Sixteen were clinical responders and 5 were non-responders. CBM predictions matched for 17 of 21 treatments overall, 15 of 16 clinical responders and 2 of 5 non-responders. The statistics of prediction accuracy against clinical outcome are presented in Table 1. Interestingly, the CBM identified drugs within the combination regimens which may not have impacted efficacy. For example, the CBM predicted that one patient treated with bortezomib, venetoclax, and dexamethasone would have had similar response if venetoclax had been omitted from the regimen. Conclusion: We have demonstrated that a CBM approach, which incorporates genomics, can help predict response in patients with relapsed or refractory MM. Prospective studies using the CBM as part of treatment decision-making will help determine its application into clinical settings. Disclosures Vij: Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jansson: Honoraria, Membership on an entity's Board of Directors or advisory committees. Singh:Cellworks Research India Private Limited: Employment. Sauban:Cellworks Research India Private Limited: Employment. Husain:Cellworks Research India Private Limited: Employment. Lakshminarayana:Cellworks Research India Private Limited: Employment. Talawdekar:Cellworks Research India Private Limited: Employment. Mitra:Cellworks Research India Private Limited: Employment. Abbasi:Cell Works Group Inc.: Employment. Vali:Cell Works Group Inc.: Employment.

Abstract Introduction; The PCR with patient-specific, allele-specific oligonucleotide primers for individual IgH VDJ regions (ASO-PCR) is considered the most sensitive method to detect minimal residual disease (MRD) levels in patients with multiple myeloma (MM). In this study, we quantified the ASO-PCR products by using peripheral blood mononuclear cells (PBMNCs) as well as bone marrow mononuclear cells (BMMNCs). We also quantified the ASO-PCR products in mRNAs from CD20+38- B-cells in BM to examine whether there are clonogenic cells in relatively earlier B-cell fraction as well as cell-free DNAs from the sera to examine whether there are DNA fragments from MM cells in PB. Materials and methods; We have analyzed 30 MM cases. After an informed consent, patient-oriented PCR primers were designed from sequence information of immunoglobulin heavy chain (IgH) variable regions of myeloma cells of each patient. Results; The median age in this cohort was 64.5 years (36-83); the ratio of men to women was 16:14; and the numbers of IgG-, IgA-, and Bence Jones protein (BJP)- type patients were 18, 7, and 5, respectively. The patient-specific ASO primers could be designed in 25 cases, but not in 3 BJP-type cases or 2 IgG-type cases. We could quantify the ASO-PCR products in 20 of 30 BMMNCs samples at diagnosis. The ASO-PCR levels (IgH/β−actin levels)in BMMNCs correlated with those in PBMNCs, but not to the percent of plasma cells in BM or the values for M-protein. However, the ASO-PCR levels were decreased after the treatment and reflected tumor burden well individually. The ASO-PCR levels in PBMNCs showed a statistically significant correlation with those in BMMNCs at diagnosis (Spearman’s ρ= 0.98, P<0.001), 6 months (Spearman’s ρ= 0.83, P = 0.020) and 12 months (Spearman’s ρ= 1.90, P = 0.001). Therefore, ASO-PCR using PBMNCs as well as BMMNCs is suitable for MRD evaluation. We could detect the patient-specific IgH DNA sequences in cell-free DNA extracted from the sera and quantify the ASO-PCR products. The sequences of the ASO-PCR product were identical to the originally designed sequence, suggesting that detection of the ASO-PCR products in cell-free DNA could reflect the persistence of myeloma cells somewhere in body. The ASO-PCR products for CD20+CD38- B-cells in BM were relatively low but were clearly detected in 17 cases at diagnosis. The ASO-PCR levels in CD20+CD38- B-cells in BM showed good correlation with both values of ASO-PCR in BMMNCs (Spearman’s ρ= 1.35, P <0.001) and in PBMNCs (Spearman’s ρ= 1.09, P <0.001). Thus, the evaluation of relatively earlier B-cell stages of myeloma cells seems to be of interst, including for the possible existence of MM clones in CD20+CD38- B-cell population in BM. Discussion; Our findings that we could quantify the ASO-PCR products in PBMNCs, BM CD20+CD38- B-cells, cell-free DNA as well as BMMNCs strongly suggest wide sources of clinical materials to analyze. There were statistically significant correlations in values of the ASO-PCR products between BMMNCs and PBMNCs, therefore suggesting the possibility that clonogenic plasma cells or myeloma precursor cells might circulate in peripheral blood. We expect the possibility that PBMNCs will be a good source to monitor MRD. We could also detect and quantify the ASO-PCR products in cell-free DNA from the sera. To the best of our knowledge, this is the first report that IgH DNA fragments from MM cells circulate in the sera. Furthermore, we could detect and quantify the ASO-PCR products in CD20+CD38- B-cells in BM at diagnosis. These results indicated that clonogenic MM cells could exist not only in the CD20-CD38high plasma cell fraction but also in the CD20+CD38- B-cell fraction, which might include myeloma stem or initiating cells. Thus, we could consider the treatment strategies to include anti-CD20 antibodies against the clonogenic CD20+CD38- B-cell population. In conclusion, our ASO-PCR using various clinical materials is supposed to be useful for detecting MRD in the patients with MM as well as for clarifying the pathogenesis of MM. Disclosures Sata: Celgen: Research Funding; Takeda: Research Funding; Janssen: Research Funding. Shibayama:Celgen: Research Funding; Takeda: Research Funding; Janssen: Research Funding. Habuchi:Celgen: Research Funding; Takeda: Research Funding; Janssen: Research Funding. Fukushima:Celgen: Research Funding; Takeda: Research Funding; Janssen: Research Funding. Fujita:Celgen: Research Funding; Takeda: Research Funding; Janssen: Research Funding. Ezoe:Celgen: Research Funding; Takeda: Research Funding; Janssen: Research Funding. Tadokoro:Celgen: Research Funding; Takeda: Research Funding; Janssen: Research Funding. Maeda:Celgen: Research Funding; Takeda: Research Funding; Janssen: Research Funding. Mizuki:Celgen: Research Funding; Takeda: Research Funding; Janssen: Research Funding. Oritani:Celgen: Research Funding; Takeda: Research Funding; Janssen: Research Funding. Kanakura:Janssen: Research Funding; Takeda: Research Funding; Celgen: Research Funding.

stater bildats på internationellt initiativ vilket verkade fungera under 40 år för Jugoslavien men de etniska motsättningarna i landet utnyttjades av nationalistiska partier efter kommunismens fall vilket trappade upp de etniska konflikterna och resulterade i ett inbördeskrig som varade i fyra år. 1994 hölls det ett fredssamtal i Dayton vilket resulterade i ett fredsavtal, The General Framework Agreement for Peace (GFAP). I GFAP gavs OSSE, som är den största regionala säkerhetsorganisationen i världen med 55 medlemsstater från Europa, Centralasien och Nordamerika, uppdraget att säkra freden och demokratisera landet. Detta innebar en demokratisering uppifrån med en begränsad möjlighet till inflytande vad det gäller den bosniska befolkningen. Detta reser frågan om denna sortens demokratiexports möjlighet till framgång? Den internationella interventionen och fredsavtalet som följde syftade inte bara till att få slut på kriget i regionen utan också till att skapa helt nya institutioner för interagerande i alla delar av statsapparaten och det civila samhället. Den demokratiska processen i Bosnien kräver väl fungerande institutioner på alla nivåer inom statsapparaten samt ett fungerande civilt samhälle. Utan dessa kan inte en demokratisering genomföras. Därför har OSSE:s demokratiseringsprojekt fokuserats på två övergripande frågor. Den ena är att omvandla institutioner från en formell demokrati med en rad officiella regelsystem, institutioner och procedurer till en substantivdemokrati inkluderande politisk jämlikhet, maktfördelning en politisk kultur och demokratisk delaktighet. Men endast demokratiska institutioner är inte nog för att skapa ett demokratiskt system, för att skapa en livskraftig och uthållig demokrati måste det även finnas en medborgarkår med demokratiska värderingar, vare sig dessa uppbringas genom propaganda eller utbildning. Därför är det fokus för OSSE att skapa ett aktivt civilt samhälle och medverkandekultur samt främja medborgarnas deltagande i statens angelägenheter. Övergångsteorin som är uppsatsen teoretiska utgångspunkt ser på demokrati som skapad av medvetna och hängivna aktörer med en vilja till kompromissande. Historiska exempel har visat att en demokratisk utveckling kan startas och lyckas även om den genomförs uppifrån och i ett samhälle som saknar en stark demokratisk kultur. Härigenom kan demokrati skapas även om människor inte vill ha den, eller kan hantera den på ett effektivt sätt. En rad projekt har startats i Bosnien för att åstadkomma denna demokratiska förändring, men framstegen har varit svåra att få till stånd samt varit tidsödande. Mycket av problematiken i Bosnien grundas i de etniska konflikterna mellan de olika grupperingarna i landet och att dessa har sina lojaliteter riktade mot andra håll än mot den Bosniska staten. Politisk konkurrens bygger fortfarande mycket på etnicitet och de bosniska politikernas har en uppenbar vana att sätta käppar i hjulen på den demokratiska processen och reformarbetet. Den djupa misstron mellan de olika etniska grupperna efter kriget och en avsaknad av en stabil demokratisk värdegrund ställer höga krav på OSSE:s arbete och har visat sig svåra att överkomma. Den demokratiska utvecklingen har gått långsamt, mycket långsammare än vad det internationella samfundet hade hoppats på, men framsteg görs. Frågan är om demokratiexport kan fungera i ett land så djupt splittrat som Bosnien, i alla fall på en så kort tid som har förflutit. Ett generationsskifte är kanske vad som behövs för att en riktig demokrati skall kunna slå rot, men omdemokratisering uppifrån kan fungera i Bosnien får tiden utvisa. Men en sak är säker Bosnien idag är en bättre plats än var den var i början av 1990-talet och OSSE:s arbete har resulterat i en framgångar.

Pourquoi et comment la Responsabilité Sociale d’Entreprise (RSE) invite-t-elle les dirigeants à redéfinir les business model ? Mettre en oeuvre la RSE signifie que l’entreprise requalifie progressivement la création de valeur au regard des valeurs universelles du développement durable. Le business model, en tant qu’outil représentatif du système de création de valeur d’une entreprise n’a plus vocation à créer uniquement de la valeur économique mais aussi des valeurs sociales, sociétales et environnementales. Le profit de l’entreprise est envisagé à travers une équation de profits au pluriel donnant du sens à la performance globale de l’entreprise.La recherche-intervention menée « avec et pour » Janssen France a permis d’élaborer et d’expérimenter un processus de création de valeurs par la RSE facilitant la prise de décision des dirigeants en la matière. Il se compose de trois séquences. Il aide les praticiens à mieux comprendre comment se définit la RSE dans le cadre de leurs activités, à structurer une orientation stratégique et à expliciter concrètement les contributions de l’entreprise aux enjeux du développement durable. En intégrant la RSE au cœur des composantes du business model, l’entreprise élargit la finalité de ses activités et contribue à des enjeux de bien commun
Why and how does Corporate Social Responsibility (CSR) invite managers to redefine business models? Implementing CSR means that the company is gradually redefining value creation according to the universal values of sustainable development. The business model, as a representative tool of a company's value creation system, no longer aims to create only economic value but also social, societal and environmental values. The profit of the company is considered through an equation of plural profits giving meaning to the overall performance of the company.The research-intervention carried out "with and for" Janssen France has made it possible to develop and test a process of values creation by CSR to facilitate decision making by managers in this area. It consists of three sequences. It helps practitioners to better understand how CSR is defined in their business, to structure a strategic orientation and to make concrete the company's contributions to sustainable development issues. By integrating CSR at the heart of the business model's components, the company broadens the scope of its activities and contributes to the common good

Les propriétés physiques des milieux granulaires trouvent leur origine à l'échelle locale des contacts entre les grains. Cette étude est consacrée à l'analyse de l'influence de ces contacts sur le comportement global du matériau à différentes échelles. Nous développons dans la première partie de ce mémoire, une approche continue qui s'affranchit des limitations de la théorie de Janssen et permet de calculer les contraintes dans un matériau granulaire ensilé. Cette approche permet également de représenter aussi bien qualitativement que quantitativement l'effet d'écrantage dans les silos. Dans une seconde partie, une modélisation du phénomène d'écrantage est effectuée à partir des simulations numériques discrètes réalisées avec le code MULTICOR. Nous calculons les contraintes moyennes s'exerçant au niveau des parois lors du remplissage d'un silo par un milieu granulaire polydisperse. Une bonne concordance est observée entre les résultats des simulations numériques discrètes et ceux de l'approche continue développée dans la première partie. Une autre conséquence de l'existence de contacts privilégiés entre les grains est l'anisotropie caractéristique des matériaux granulaires. Dans la dernière partie, nous développons une approche micromécanique qui permet de modéliser cette anisotropie par l'intermédiaire d'un tenseur de texture d'ordre quatre. Nous proposons une hypothèse cinématique générale qui est incorporée dans un schéma d'homogénéisation des milieux granulaires anisotropes et comparée, dans le cas isotrope, à des simulations numériques discrètes existant dans la littérature. Les tendances qualitatives et quantitatives des résultats sont tout à fait satisfaisantes.

The processes of internationalization and political economic transformation described in the previous chapters help explain the specific character of recent industrial development in Thailand. Capital accumulation in Thailand has been centred heavily on Bangkok and has favoured a stratum of ruling elites who are disproportionately represented in the capital. The Bangkok-centric political economy has been tightly linked—indeed, over a very long period of time—with broader regional and international processes of capital accumulation, and the Thai elites have been successful at using international connections to buttress their social positions and control. Bangkok elites, in particular, have been able to utilize international support to strengthen a project of Bangkok sub-imperialism, which has in turn brought various local elites from outside Bangkok into national and international coalitions. All of this has consequences for the results of economic growth and industrial transformation in Thailand. Until the economic meltdown that began in 1996, Thailand’s GDP growth record was one of the most impressive in the world since World War II, and the country was included by the World Bank among the ‘miracle’ economies of East Asia (World Bank 1993), while being lauded by others as ‘the Fifth Tiger’ (Muscat 1994) and as a new entrant into the ranks of the NICs (Jansen 1991). At the same time, Thailand has become one of the more inegalitarian countries in the world, in terms of income distribution (Medhi 1996; Voravidh 1996) and displays a dramatic spatial skew in the distribution of economic activities. There have also been numerous social and environmental problems connected with industrial development in Thailand, along with various political indignities to the general population (Bello, Cunningham, and Poh 1998)—problems that can be seen alternatively as ‘the strains of success’ (UNIDO 1992) or as symptoms of ‘maldevelopment’ (Suthy 1991). To some extent, each of these images of success and failure correspond to a definite reality of the complex development process, neither of which by itself adequately summarizes the totality. What I focus on in this chapter, however, is not the multifaceted complexity per se but rather the connections between what are regarded as the success and failure stories.

The coronary flow reserve (CFR) represents an important functional parameter to assess epicardial coronary stenosis and to evaluate the integrity of coronary microcirculation (Kern, 2000; Sadamatsu, Tashiro, Maehira, & Yamamoto, 2000). CFR can be measured, during adenosine or dipyridamole infusion, as the ratio of maximal (pharmacologically stimulated) to baseline (resting) diastolic coronary blood flow peak. Even in absence of stenosis in epicardial coronary artery, the CFR may be decreased when coronary microvascular circulation is compromised by arterial hypertension with or without left ventricular hypertrophy, diabetes mellitus, hypercholesterolemia, syndrome X, hypertrophic cardiomyopathy, and connective tissue diseases (Dimitrow, 2003; Strauer, Motz, Vogt, & Schwartzkopff, 1997). Several methods have been established for measuring CFR: invasive (intracoronary Doppler flow wire) (Caiati, Montaldo, Zedda, Bina, & Iliceto, 1999b; Lethen, Tries, Brechtken, Kersting, & Lambertz, 2003a; Lethen, Tries, Kersting, & Lambertz, 2003b), semi-invasive and scarcely feasible (transesophageal Doppler echocardiography) (Hirabayashi, Morita, Mizushige, Yamada, Ohmori, & Tanimoto, 1991; Iliceto, Marangelli, Memmola, & Rizzon, 1991; Lethen, Tries, Michel, & Lambertz, 2002; Redberg, Sobol, Chou, Malloy, Kumar, & Botvinick, 1995), or extremely expensive and scarcely available methods (PET, SPECT, MRI) (Caiati, Cioglia, Montaldo, Zedda, Rubini, & Pirisi, 1999a; Daimon, Watanabe, Yamagishi, Muro, Akioka, & Hirata, 2001; Koskenvuo, Saraste, Niemi, Knuuti, Sakuma, & Toikka, 2003; Laubenbacher, Rothley, Sitomer, Beanlands, Sawada, & Sutor, 1993; Picano, Parodi, Lattanzi, Sambuceti, Andrade, & Marzullo, 1994; Saraste, Koskenvuo, Knuuti, Toikka, Laine, & Niemi, 2001; Williams, Mullani, Jansen, & Anderson, 1994), thus their clinical use is limited (Dimitrow, 2003). In addition, PET and intracoronary Doppler flow wire involve radiation exposure, with inherent risk, environmental impact, and biohazard connected with use of ionizing testing (Picano, 2003a). In the last decade, the development of new ultrasound equipments and probes has made possible the noninvasive evaluation of coronary blood velocity by Doppler echocardiography, using a transthoracic approach. In this way, the peak diastolic coronary flow velocity reserve (CFVR) can be estimated as the ratio of the maximal (pharmacologically stimulated) to baseline (resting) diastolic coronary blood flow velocity peak measured from the Doppler tracings. Several studies have shown that peak diastolic CFVR, computed in the distal portion of the left anterior descending (LAD) coronary artery, correlates with CFR obtained by more invasive techniques. This provided a reliable and non invasive tool for the diagnosis of LAD coronary artery disease (Caiati et al., 1999b; Caiati, Montaldo, Zedda, Montisci, Ruscazio, & Lai, 1999c; Hozumi, Yoshida, Akasaka, Asami, Ogata, & Takagi, 1998; Koskenvuo et al., 2003; Saraste et al., 2001).

Great River Energy operates a waste-to-energy plant in Elk River, Minnesota. The plant burns 850 tons per day of refuse derived fuel (RDF) in three boilers, and its three steam turbines can produce 32 MW of electricity. In the largest of the three units, the No. 3 Boiler, steam generation was restricted by carbon monoxide (CO) and nitrogen oxides (NOx) emission limits. The plant had an interest in improving the combustion performance of the unit, thereby allowing higher average RDF firing rates while staying within emissions compliance. The project was initiated by an engineering site visit and evaluation. The boiler had a history of unstable burning on the stoker grate, which required periodic natural gas co-firing to reduce CO levels. As an outcome to the evaluation, it was decided to install a new overfire air (OFA) system to improve burnout of combustible gases above the grate. Current and new OFA arrangements were evaluated via Computational Fluid Dynamics (CFD) modeling. The results illustrated the limitations of the original OFA system (comprised of multiple rows of small OFA ports on the front and rear furnace walls), which generated inadequate mixing of air and combustible gases in the middle of the boiler. The modeling illustrated the advantages of large and fewer OFA nozzles placed on the side walls in an interlaced pattern, a configuration that has given excellent performance on over 45 biomass-fired boilers of similar design upgraded by Jansen Combustion and Boiler Technologies, Inc. (JANSEN). Installation of the new OFA system was completed in April of 2008. Subsequent testing of the No. 3 Boiler showed that it could reliably meet the state emission levels for CO and NOx (200 ppm and 250 ppm, respectively, corrected to 7% dry flue gas oxygen) while generating 24% more steam than a representative five month period prior to the upgrade. This paper describes the elements that led to a successful project, including: data collection, engineering analyses, CFD modeling, system design, equipment supply, installation, operator training, and startup assistance.