Effects of infliximab on markers of inflammation and bone turnover and associations with bone mineral density in patients with ankylosing spondylitis

Using a micro-extruder a new class of polyurethanes, polyacylurethanes (PAUs), based on poly (epsilon-caprol actone) (PCL) oligomers and terephthaloyl diisocyanate was synthesized. These polymers are anticipated to have potential for biodegradable and/or biomedical applications. Therefore, PAUs were synthesized without the use of any, possibly toxic, catalysts. PCL diols of different molecular mass were used, namely 750, 1000, 1250, 1500, 2000, 3000 and 4000 g/mol. These diols were synthesized by thermal polymerization at 150 degrees C without the use of any catalyst. The PAUs of terephthaloyl diisocyanate were synthesized by reactive extrusion using a micro-extruder of 5 cm 3 at 130 degrees C. The PAUs obtained were characterized using DSC, GPC, DMTA, SAXS and tensile testing. Surprisingly, PAUs based on PCL chains of 750, 1000, 1250 and 1500 g/mol were found to show microphase separation/micro crystallization as proven by SAXS data combined with DSC. This microphase separation creates elastomeric properties as is known from polyurethanes. In the PAUs based on PCL chains of 2000, 3000 and 4000 g/mol part of the PCL was found to crystallize and no evidence of any phase separation of the acylurethane block was found. (c) 2005 Elsevier Ltd. All rights reserved

The nil Hecke ring and singularity of Schubert varieties

We give a criterion for smoothness of a point in any Schubert variety in any G/B in terms of the nil Hecke ring.Comment: AMSTE

GALEX J201337.6+092801: The lowest gravity subdwarf B pulsator

We present the recent discovery of a new subdwarf B variable (sdBV), with an exceptionally low surface gravity. Our spectroscopy of J20136+0928 places it at Teff = 32100 +/- 500, log(g) = 5.15 +/- 0.10, and log(He/H) = -2.8 +/- 0.1. With a magnitude of B = 12.0, it is the second brightest V361 Hya star ever found. Photometry from three different observatories reveals a temporal spectrum with eleven clearly detected periods in the range 376 to 566 s, and at least five more close to our detection limit. These periods are unusually long for the V361 Hya class of short-period sdBV pulsators, but not unreasonable for p- and g-modes close to the radial fundamental, given its low surface gravity. Of the ~50 short period sdB pulsators known to date, only a single one has been found to have comparable spectroscopic parameters to J20136+0928. This is the enigmatic high-amplitude pulsator V338 Ser, and we conclude that J20136+0928 is the second example of this rare subclass of sdB pulsators located well above the canonical extreme horizontal branch in the HR diagram.Comment: 5 pages, accepted for publication in ApJ Letter

Irreducible Characters of General Linear Superalgebra and Super Duality

We develop a new method to solve the irreducible character problem for a wide class of modules over the general linear superalgebra, including all the finite-dimensional modules, by directly relating the problem to the classical Kazhdan-Lusztig theory. We further verify a parabolic version of a conjecture of Brundan on the irreducible characters in the BGG category \mc{O} of the general linear superalgebra. We also prove the super duality conjecture

Super duality and irreducible characters of ortho-symplectic Lie superalgebras

We formulate and establish a super duality which connects parabolic categories $O$ between the ortho-symplectic Lie superalgebras and classical Lie algebras of $BCD$ types. This provides a complete and conceptual solution of the irreducible character problem for the ortho-symplectic Lie superalgebras in a parabolic category $O$, which includes all finite-dimensional irreducible modules, in terms of classical Kazhdan-Lusztig polynomials.Comment: 30 pages, Section 5 rewritten and shortene

The Kazhdan-Lusztig conjecture for finite W-algebras

We study the representation theory of finite W-algebras. After introducing parabolic subalgebras to describe the structure of W-algebras, we define the Verma modules and give a conjecture for the Kac determinant. This allows us to find the completely degenerate representations of the finite W-algebras. To extract the irreducible representations we analyse the structure of singular and subsingular vectors, and find that for W-algebras, in general the maximal submodule of a Verma module is not generated by singular vectors only. Surprisingly, the role of the (sub)singular vectors can be encapsulated in terms of a `dual' analogue of the Kazhdan-Lusztig theorem for simple Lie algebras. These involve dual relative Kazhdan-Lusztig polynomials. We support our conjectures with some examples, and briefly discuss applications and the generalisation to infinite W-algebras.Comment: 11 page

Effect of secukinumab on clinical and radiographic outcomes in ankylosing spondylitis: 2-year results from the randomised phase III MEASURE 1 study.

OBJECTIVE: To evaluate the effect of secukinumab, an interleukin-17A inhibitor, on clinical signs and symptoms and radiographic changes through 2 years in patients with ankylosing spondylitis (AS). METHODS: In the phase III MEASURE 1 study, patients were randomised to receive intravenous secukinumab 10 mg/kg (at baseline, week 2 and week 4) followed by subcutaneous secukinumab 150 mg (intravenous 150 mg; n=125) or 75 mg (intravenous 75 mg; n=124) every four weeks, or matched placebo (n=122). Placebo-treated patients were re-randomised to subcutaneous secukinumab 150 or 75 mg from week 16. Clinical efficacy assessments included Assessment of SpondyloArthritis international Society 20 (ASAS20) response rates through week 104. Radiographic changes at week 104 were assessed using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). RESULTS: 97 (77.6%) and 103 (83.1%) patients in the intravenous 150 mg and intravenous 75 mg groups, respectively, completed week 104. In the full analysis set (intent-to-treat), ASAS20 response rates at week 104 were 73.7% and 68.0% in the intravenous 150 mg and intravenous 75 mg groups, respectively. Among patients with evaluable X-rays who were originally randomised to secukinumab (n=168), mean change in mSASSS from baseline to week 104 was 0.30±2.53. Serious adverse events were reported in 12.2% and 13.4% of patients in the 150 mg and 75 mg groups, respectively. CONCLUSIONS: Secukinumab improved AS signs and symptoms through 2 years of therapy, with no unexpected safety findings. Data from this study suggest a low mean progression of spinal radiographic changes, which will need to be confirmed in longer-term controlled studies. TRIAL REGISTRATION NUMBER: NCT01358175

Clinical Evaluation of Tolmetin

A clincial therapeutic trial of tolmetin in daily doses of 1200 and 1600 mg. is reported in 16 patients with rheumatoid arthritis. The drug was given for a period of two weeks at both dose levels. Significant improvement was noted with both dose levels in painrelief, articular tenderness and grip strength, but no significant differences were noted between the two dosages. An anti-inflammatory effect could not be demonstrated. Five of the 16 patients had to discontinue therapy at the lower dose due to gastric intolerance

Induction of sustained clinical remission in early axial spondyloarthritis following certolizumab pegol treatment: 48-week outcomes from C-OPTIMISE

INTRODUCTION: Achievement of remission is a key treatment goal for patients with axial spondyloarthritis (axSpA). C-OPTIMISE assessed achievement of sustained clinical remission in patients with axSpA, including radiographic (r) and non-radiographic (nr) axSpA, during certolizumab pegol (CZP) treatment, and subsequent maintenance of remission following CZP dose continuation, dose reduction or withdrawal. Here, we report outcomes from the first 48 weeks (induction period) of C-OPTIMISE, during which patients received open-label CZP. METHODS: C-OPTIMISE (NCT02505542) was a two-part, multicenter, phase 3b study in adult patients with early axSpA (r-/nr-axSpA), including a 48-week open-label induction period followed by a 48-week maintenance period. Patients with active adult-onset axSpA, < 5 years' symptom duration, and fulfilling Assessment of SpondyloArthritis international Society classification criteria, were included. During the induction period, patients received a loading dose of CZP 400 mg at weeks 0, 2, and 4, followed by CZP 200 mg every 2 weeks (Q2W) up to week 48. The main outcome of the 48-week induction period was the achievement of sustained clinical remission (defined as an Ankylosing Spondylitis Disease Activity Score [ASDAS] < 1.3 at week 32 and < 2.1 at week 36 [or vice versa], and < 1.3 at week 48). RESULTS: In total, 736 patients (407 with r-axSpA, 329 with nr-axSpA) were enrolled into the study. At week 48, 43.9% (323/736) of patients achieved sustained remission, including 42.8% (174/407) of patients with r-axSpA and 45.3% (149/329) with nr-axSpA. Patients also demonstrated substantial improvements in axSpA symptoms, MRI outcomes and quality of life measures. Adverse events occurred in 67.9% (500/736) of patients, of which 6.0% (44/736) were serious. CONCLUSIONS: Over 40% of patients with early axSpA achieved sustained remission during 48 weeks of open-label CZP treatment. Additionally, patients across the axSpA spectrum demonstrated substantial improvements in imaging outcomes and quality of life following treatment. No new safety signals were identified. TRIAL REGISTRATION: NCT02505542