Age affects joint space narrowing in patients with early active rheumatoid arthritis

Background: Joint space narrowing ( JSN) in rheumatoid arthritis (RA) may be a manifestation of (primary) osteoarthritis becoming more prominent with age. We investigated the severity and predictors of JSN progression among different age groups. Methods: 10-year follow-up data of the BeSt study, a randomised controlled treat-to-target trial in early RA were used. Annual X-rays of hands and feet were scored using the Sharp/van der Heijde score (SHS). Subgroups were defined by age at baseline: 55, 40<55 and <40 years. JSN progression predictors were assessed by Poisson regression. Results: Baseline JSN scores (median (IQR)) were igher in patients 55 (2.0 (0.0-6.0)) compared with the other age groups: 1.0 (0.0-3.0) 40<55 and 0.3 (0.0-3.0) <40, p<0.001. After 10 years, total JSN and SHS were similar in all age groups. In patients 55 the mean erythrocyte sedimentation rate (ESR) over time (relative risk 1.02 (95% CI 1.00 to 1.03)

Two-year results of disease activity score (DAS)-remission-steered treatment strategies aiming at drug-free remission in early arthritis patients (the IMPROVED-study)

Background: Early suppression of disease activity in (rheumatoid) arthritis (RA) patients may result in drug-free remission and prevent damage. We assessed 2-year clinical and radiological outcomes of two disease activity score (DAS)-remission-steered treatment strategies in early arthritis patients.Methods: Patients (n = 610) with early RA or undifferentiated arthritis (UA) were treated with methotrexate (MTX) and tapered high dose of prednisone. Patients in early remission (44/53 joints DAS <1.6) after 4 months tapered and stopped medication. Patients who did not achieve early DAS-remission were randomized to either MTX plus hydroxychloroquine plus sulphasalazine plus low dose prednisone (arm 1) or to MTX + adalimumab (arm 2). At four-monthly intervals, medication was tapered and stopped if DAS was <1.6 but restarted, increased or switched if DAS was ≥1.6. Proportions of (drug-free) DAS-remission (DFR) after 2 years and Sharp-van der Heijde scores (SHS) were analyzed separately for the treatment strategies and patients with RA and UA.Results: After 2 years, 301/610 (49 %) patients were in DAS-remission and 131/610 (21 %) in DFR. In the early remission group 241/387 patients (62 %) were in DAS-remission and 111/387 (29 %) DFR. In arm 1 22/83 (27 %) and in arm 2 24/78 (31 %) were in DAS-remission, and 6/83 (7 %) and 7/78 (9 %), respectively, were in DFR. RA and UA patients achieved DAS-remission in comparable percentages (RA: 234/479 (49 %), UA: 64/122 (52 %), p = 0.25). More UA patients achieved DFR (41/122 (34 %)) compared to RA patients (89/479 (19 %), p<0.001). Mean (SD) DAS over time was 1.74 (0.58) across all patients, and median (IQR) SHS progression was 0 (0–0).Conclusions: After 2 years remission-steered treatment in early RA and UA patients, DAS-remission and DFR percentages were relatively low. Patients who achieved early remission more often achieved (drug-free) remission after 2 years than patients who needed additional treatment steps in the randomization arms, and more UA than RA patients achieved DFR. Overall, disease activity and radiologic damage progression in all patients were well suppressed.Trial registration: http://www.controlled-trials.com/ISRCTN11916566 Registered 07/11/2006 and EudraCT number 2006-06186-16 Registered 16/07/2007

Mimari Unsurlardan Sanatsal İmgelere

İn the report of ''From Architectural Elements To Artistic İmages'' setting up structure of human and the development of living materials to meet the needs of this actıonis handled with artistic perspective. From the beginning of civilization to these days, this change in architectural materials had changed the band between human . From the cave where the first human lived, to the huge skyscrapers of today the greatest contribution to the development of this process was the production of steam engines caused the change in the perspective of ındustnallization and mechenization of objects. The producing man has become the designer of the produced material 20 th century art is importent for human history. This is the age of revolution and transformation in art and in all the fields and this era continues to exist in the 21 st century. This state of understanding of the new from is introduced by ıncorporating the concept of new material into the art by rebuilding all the components of art, by the concept of socialproduction, the process of mental design instead of art she expression, the reconstruction of the entire universe with the functional structure and developing technolgy, the effect of the artist factor transposed..With this situation which has turred into the development of imaginative cannections of the artist and his art in the field of art and the accepton a of the materials he uses, the meanings of comparison and encounter are challanged to the viewer through the object and the usewer is transformed into a part of the work. İn this contexts have been created by using different architectural objects and patterns taken from different materials. Thereflections of the architectural elements in art, which are transferred by destroying the existing object from its meaning, are analyzed with applications.ÖZ............................................................................................................................................i ABSTRACT...........................................................................................................................ii TEŞEKKÜR..........................................................................................................................iii İÇİNDEKİLER DİZİNİ.........................................................................................................iv GÖRSEL DİZİNİ...................................................................................................................v 1. BÖLÜM: YAPI ENDÜSTRİSİ VE MİMARİ UNSURLAR............................................1 2. BÖLÜM: MİMARİ UNSURLARIN SANATTAKİ YERİ.............................................11 2.1.Konstrüktivizim............................................................................................12 2.2. Bauhaus........................................................................................................15 2.3. Minimalizm..................................................................................................18 2.4. Modernizm ve Sonrası.................................................................................23 3. BÖLÜM: UYGULAMALAR..........................................................................................34 SONUÇ.................................................................................................................................57 KAYNAKLAR.....................................................................................................................58 ETİK BEYANI.....................................................................................................................60 YÜKSEK LİSANS SANAT ÇALIŞMASI RAPORU ORJİNALLİK RAPORU...............61 MATER‟S ART WORK REPORT ORIGINALITY REPORT...........................................62 YAYIMLAMA VE FİKRÎ MÜLKİYET HAKLARI BEYANI..........................................63''Mimari Unsurlardan Sanatsal İmgelere'' başlıklı raporda insanın yapı oluşturma eylemi ve bu eylemindeki ihtiyacı karşılayabilmek için kullandığı yaşam malzemelerinin gelişimi ve değişimi sanatsal perspektif doğrultusunda ele alınmıştır. İlk önceleri kendisini doğayla bir gören ya da ayırt edemeyen ve bu durumu kabullenip ona uyum sağlayan insan, belirli bir süre sonra bilinçlenip kendisini özne olarak merkeze alırken, nesnel dünyayı karşısına alıp doğa üzerinde hâkimiyet kurma serüvenini başlatmıştır. İnsan çevresini etkileyen ve bulunduğu çevreden etkilenen, sürekli yeni oluşumlar yaratan ve bu oluşumlarda yer alan bir canlıdır. Uygarlığın başlangıcından günümüze mimari malzemelerde yaşanan bu değişim zamanla insanın malzemeyle kurduğu bağı da değiştirmiştir. İlk insanın yaşadığı mağaradan başlayıp, günümüzün devasa gökdelenlerine gelen bu süreçteki değişime en büyük katkıyı sağlayan buharlı makinelerin üretilmesi, sanayileşme ve makineleşme, nesnelere bakış açısının değişmesine neden olmuştur. 20. yüzyıl tüm alanlarda devrim ve dönüşümlerin çağıdır ve bu durum 21. yüzyılda da sürekliliğini korumaktadır. Yeni biçim anlayışlarının ortaya konduğu bu durum, yeni malzeme anlayışını sanatın içerisine dahil ederek, sanatın bütün bileşenlerini yeniden inşa edip, toplumsal üretim anlayışıyla, sanatsal dışavurumun yerine zihinsel tasarım sürecini, işlevsel strüktür ve gelişen teknolojiyle beraber değişen tüm evrenin yeniden inşası, sanatçı faktörünün etkisi üzerinden aktarılmıştır. Bu bağlamda çalışmalarda kullanılan, farklı mimari nesneler ve nesnelerin farklı malzemelerle alınan kalıplarıyla yeni anlamlar ve bağlamlar oluşturulmuştur. Var olan nesnenin anlamından kopartılmasıyla, bağlamının yok edilerek aktarıldığı mimari unsurların sanattaki yansımaları uygulamalarla irdelenmiştir

Synthesis and biological evaluation of new chloro/acetoxy substituted isoindole analogues as new tyrosine kinase inhibitors

Köse, Aytekin ( Aksaray, Yazar )We have developed a versatile synthetic approach for the synthesis of new isoindole derivatives via the cleavage of ethers from tricyclic imide skeleton compounds. An exo-cycloadduct prepared from the Diels–Alder reaction of furan and maleic anhydride furnished imide derivatives. The epoxide ring was opened with Ac2O or Ac2O/AcCl in the presence of a catalytic amount of H2SO4 in order to yield new isoindole derivatives 8a-d and 9a-d. The anticancer activity of these compounds was evaluated against the HeLa cell lines. The synthesized compounds showed inhibitory effects on the viability of HeLa cells and the degree of cytotoxicity was increased with the level of bigger branched isoindole derivatives. To better understand the acting mechanism of these molecules, western blot analysis was performed with using mTOR and its downstream substrates. In addition, human mTOR and ribozomal S6 kinase β1 (RS6Kβ1) have been investigated with molecular modelling studies as possible targets for compound series 8 and 9

Additional file 1 of Further Treatment Intensification in Undifferentiated and Rheumatoid Arthritis Patients Already in Low Disease Activity has Limited Benefit towards Physical Functioning

Number of patients in low disease activity with or without protocol violation for each visit. (DOCX 210 kb

Repair of joint damage in patients with rheumatoid arthritis does not relate to previous suppression of inflammation: a subanalysis after 8 years treat-to-target in the BeSt-trial

Objectives To investigate whether repair of erosions and joint space narrowing (JSN) in rheumatoid arthritis (RA) occurs and whether clinical variables predict this.Methods Eight-year follow-up data of the BeSt-study were used. Patients with recent onset RA (1987 criteria) were randomised to four treatment strategies and treated-to-target (Disease Activity Score (DAS)≤2.4). Yearly radiographs of hands and feet were scored in non-chronological order by four independent readers, using the Sharp/van der Heijde score (SHS). Damage repair was defined as a negative ΔSHS in an individual joint, seen by ≥3 out of 4 readers and persisting ≥2 consecutive years. Associations between repair and DAS, prednisone use, infliximab use, anticitrullinated protein antibody, gender, age, body mass index, symptom duration and randomisation arm were investigated with logistic regression analyses, corrected for mean SHS.Results Repair was seen in 17 patients (5.3%); 10 had regression of JSN, 7 of erosions, none had both. There were no significant associations in any of the regression analyses.Conclusion After 8 years of treatment to target DAS≤2.4 in 508 patients with recent onset RA, repair of JSN and erosions was seen in 17/320 patients (5.3%). Probably due to the rarity of repair, we found no associations with suppression of disease activity or other predictors and repair

Incidence and risk factors for adalimumab and infliximab anti-drug antibodies in rheumatoid arthritis: A European retrospective multicohort analysis

International audienceOBJECTIVES:To evaluate the incidence of anti-drug antibody (ADA) occurrences and ADA-related risk factors under adalimumab and infliximab treatment in rheumatoid arthritis (RA) patients.METHODS:The study combined retrospective cohorts from the ABIRISK project totaling 366 RA patients treated with adalimumab (n = 240) or infliximab (n = 126), 92.4% of them anti-TNF naive (n = 328/355) and 96.6% of them co-treated with methotrexate (n = 341/353) with up to 18 months follow-up. ADA positivity was measured by enzyme-linked immunosorbent assay. The cumulative incidence of ADA was estimated, and potential bio-clinical factors were investigated using a Cox regression model on interval-censored data.RESULTS:ADAs were detected within 18 months in 19.2% (n = 46) of the adalimumab-treated patients and 29.4% (n = 37) of the infliximab-treated patients. The cumulative incidence of ADA increased over time. In the adalimumab and infliximab groups, respectively, the incidence was 15.4% (5.2-20.2) and 0% (0-5.9) at 3 months, 17.6% (11.4-26.4) and 0% (0-25.9) at 6 months, 17.7% (12.6-37.5) and 34.1% (11.4-46.3) at 12 months, 50.0% (25.9-87.5) and 37.5% (25.9-77.4) at 15 months and 50.0% (25.9-87.5) and 66.7% (37.7-100) at 18 months. Factors associated with a higher risk of ADA development were: longer disease duration (1-3 vs. < 1 year; adalimumab: HR 3.0, 95% CI 1.0-8.7; infliximab: HR 2.7, 95% CI 1.1-6.8), moderate disease activity (DAS28 3.2-5.1 vs. < 3.2; adalimumab: HR 6.6, 95% CI 1.3-33.7) and lifetime smoking (infliximab: HR 2.7, 95% CI 1.2-6.3).CONCLUSIONS:The current study focusing on patients co-treated with methotrexate for more than 95% of them found a late occurrence of ADAs not previously observed, whereby the risk continued to increase over 18 months. Disease duration, DAS28 and lifetime smoking are clinical predictors of ADA development