Coloured peak algebras and Hopf algebras

For $G$ a finite abelian group, we study the properties of general equivalence relations on G_n=G^n\rtimes \SG_n, the wreath product of $G$ with the symmetric group \SG_n, also known as the $G$-coloured symmetric group. We show that under certain conditions, some equivalence relations give rise to subalgebras of \k G_n as well as graded connected Hopf subalgebras of \bigoplus_{n\ge o} \k G_n. In particular we construct a $G$-coloured peak subalgebra of the Mantaci-Reutenauer algebra (or $G$-coloured descent algebra). We show that the direct sum of the $G$-coloured peak algebras is a Hopf algebra. We also have similar results for a $G$-colouring of the Loday-Ronco Hopf algebras of planar binary trees. For many of the equivalence relations under study, we obtain a functor from the category of finite abelian groups to the category of graded connected Hopf algebras. We end our investigation by describing a Hopf endomorphism of the $G$-coloured descent Hopf algebra whose image is the $G$-coloured peak Hopf algebra. We outline a theory of combinatorial $G$-coloured Hopf algebra for which the $G$-coloured quasi-symmetric Hopf algebra and the graded dual to the $G$-coloured peak Hopf algebra are central objects.Comment: 26 pages latex2

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

Mask formulas for cograssmannian Kazhdan-Lusztig polynomials

We give two contructions of sets of masks on cograssmannian permutations that can be used in Deodhar's formula for Kazhdan-Lusztig basis elements of the Iwahori-Hecke algebra. The constructions are respectively based on a formula of Lascoux-Schutzenberger and its geometric interpretation by Zelevinsky. The first construction relies on a basis of the Hecke algebra constructed from principal lower order ideals in Bruhat order and a translation of this basis into sets of masks. The second construction relies on an interpretation of masks as cells of the Bott-Samelson resolution. These constructions give distinct answers to a question of Deodhar.Comment: 43 page

Short-term changes on MRI predict long-term changes on radiography in rheumatoid arthritis: an analysis by an OMERACT Task Force of pooled data from four randomised controlled trials

Objective: In rheumatoid arthritis (RA), MRI provides earlier detection of structural damage than radiography (X-ray) and more sensitive detection of intra-articular inflammation than clinical examination. This analysis was designed to evaluate the ability of early MRI findings to predict subsequent structural damage by X-ray. Methods: Pooled data from four randomised controlled trials (RCTs) involving 1022 RA hands and wrists in early and established RA were analysed. X-rays were scored using van der Heijde-modified or Genant-modified Sharp methods. MRIs were scored using Outcome Measures in Rheumatology (OMERACT) RA MRI Score (RAMRIS). Data were analysed at the patient level using multivariable logistic regression and receiver operating characteristic curve analyses. Results: Progression of MRI erosion scores at Weeks 12 and 24 predicted progression of X-ray erosions at Weeks 24 and 52, with areas under the curve (AUCs) of 0.64 and 0.74, respectively. 12-week and 24-week changes in MRI osteitis scores were similarly predictive of 24-week and 52-week X-ray erosion progressions; pooled AUCs were 0.78 and 0.77, respectively. MRI changes in synovitis at Weeks 12 and 24 also predicted progression of X-ray joint damage (erosion and joint-space narrowing) at Weeks 24 and 52 (AUCs=0.72 and 0.65, respectively). Conclusions: Early changes in joint damage and inflammation detected with MRI predict changes in joint damage evident on subsequent X-rays. These findings support the use of MRI as a valid method for monitoring structural damage in short-duration RCTs

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

Long-term safety of secukinumab in patients with moderate-to-severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis: integrated pooled clinical trial and post-marketing surveillance data

Background: Secukinumab, a fully human immunoglobulin G1-kappa monoclonal antibody that directly inhibits interleukin (IL)-17A, has been shown to have robust efficacy in the treatment of moderate-to-severe psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) demonstrating a rapid onset of action and sustained long-term clinical responses with a consistently favorable safety profile in multiple Phase 2 and 3 trials. Here, we report longer-term pooled safety and tolerability data for secukinumab across three indications (up to 5 years of treatment in PsO and PsA; up to 4 years in AS). Methods: The integrated clinical trial safety dataset included data pooled from 21 randomized controlled clinical trials of secukinumab 300 or 150 or 75 mg in PsO (14 Phase 3 trials and 1 Phase 4 trial), PsA (3 Phase 3 trials), and AS (3 Phase 3 trials), along with post-marketing safety surveillance data with a cut-off date of June 25, 2017. Adverse events (AEs) were reported as exposure-adjusted incident rates (EAIRs) per 100 patient-years. Analyses included all patients who received ≥ 1 dose of secukinumab. Results: A total of 5181, 1380, and 794 patients from PsO, PsA, and AS clinical trials representing secukinumab exposures of 10,416.9, 3866.9, and 1943.1 patient-years, respectively, and post-marketing data from patients with a cumulative exposure to secukinumab of ~ 96,054 patient-years were included in the analysis. The most frequent AE was upper respiratory tract infection. EAIRs across PsO, PsA, and AS indications were generally low for serious infections (1.4, 1.9, and 1.2, respectively), Candida infections (2.2, 1.5, and 0.7, respectively), inflammatory bowel disease (0.01, 0.05, and 0.1, respectively), and major adverse cardiac events (0.3, 0.4, and 0.6, respectively). No cases of tuberculosis reactivation were reported. The incidence of treatment-emergent anti-drug antibodies was low with secukinumab across all studies, with no discernible loss of efficacy, unexpected alterations in pharmacokinetics, or association with immunogenicity-related AEs. Conclusions: Secukinumab demonstrated a favorable safety profile over long-term treatment in patients with PsO, PsA, and AS. This comprehensive assessment demonstrated that the safety profile of secukinumab was consistent with previous reports in patients with PsO, PsA, and AS, supporting its long-term use in these chronic conditions

Long-term safety of secukinumab in patients with moderate-to-severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis: integrated pooled clinical trial and post-marketing surveillance data.

BACKGROUND: Secukinumab, a fully human immunoglobulin G1-kappa monoclonal antibody that directly inhibits interleukin (IL)-17A, has been shown to have robust efficacy in the treatment of moderate-to-severe psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) demonstrating a rapid onset of action and sustained long-term clinical responses with a consistently favorable safety profile in multiple Phase 2 and 3 trials. Here, we report longer-term pooled safety and tolerability data for secukinumab across three indications (up to 5 years of treatment in PsO and PsA; up to 4 years in AS). METHODS: The integrated clinical trial safety dataset included data pooled from 21 randomized controlled clinical trials of secukinumab 300 or 150 or 75 mg in PsO (14 Phase 3 trials and 1 Phase 4 trial), PsA (3 Phase 3 trials), and AS (3 Phase 3 trials), along with post-marketing safety surveillance data with a cut-off date of June 25, 2017. Adverse events (AEs) were reported as exposure-adjusted incident rates (EAIRs) per 100 patient-years. Analyses included all patients who received ≥ 1 dose of secukinumab. RESULTS: A total of 5181, 1380, and 794 patients from PsO, PsA, and AS clinical trials representing secukinumab exposures of 10,416.9, 3866.9, and 1943.1 patient-years, respectively, and post-marketing data from patients with a cumulative exposure to secukinumab of ~ 96,054 patient-years were included in the analysis. The most frequent AE was upper respiratory tract infection. EAIRs across PsO, PsA, and AS indications were generally low for serious infections (1.4, 1.9, and 1.2, respectively), Candida infections (2.2, 1.5, and 0.7, respectively), inflammatory bowel disease (0.01, 0.05, and 0.1, respectively), and major adverse cardiac events (0.3, 0.4, and 0.6, respectively). No cases of tuberculosis reactivation were reported. The incidence of treatment-emergent anti-drug antibodies was low with secukinumab across all studies, with no discernible loss of efficacy, unexpected alterations in pharmacokinetics, or association with immunogenicity-related AEs. CONCLUSIONS: Secukinumab demonstrated a favorable safety profile over long-term treatment in patients with PsO, PsA, and AS. This comprehensive assessment demonstrated that the safety profile of secukinumab was consistent with previous reports in patients with PsO, PsA, and AS, supporting its long-term use in these chronic conditions

Determinants of Acceptance of Cervical Cancer Screening in Dar es Salaam, Tanzania.

To describe how demographic characteristics and knowledge of cervical cancer influence screening acceptance among women living in Dar es Salaam, Tanzania. Multistage cluster sampling was carried out in 45 randomly selected streets in Dar es Salaam. Women between the ages of 25-59 who lived in the sampled streets were invited to a cervical cancer screening; 804 women accepted and 313 rejected the invitation. Information on demographic characteristics and knowledge of cervical cancer were obtained through structured questionnaire interviews. Women aged 35-44 and women aged 45-59 had increased ORs of 3.52 and 7.09, respectively, for accepting screening. Increased accepting rates were also found among single women (OR 2.43) and among women who had attended primary or secondary school (ORs of 1.81 and 1.94). Women who had 0-2 children were also more prone to accept screening in comparison with women who had five or more children (OR 3.21). Finally, knowledge of cervical cancer and awareness of the existing screening program were also associated with increased acceptance rates (ORs of 5.90 and 4.20). There are identifiable subgroups where cervical cancer screening can be increased in Dar es Salaam. Special attention should be paid to women of low education and women of high parity. In addition, knowledge and awareness raising campaigns that goes hand in hand with culturally acceptable screening services will likely lead to an increased uptake of cervical cancer screening

Referral patterns, diagnosis, and disease management of patients with axial spondyloarthritis: results of an international survey

Background: Recognition, diagnosis, and management of axial spondyloarthritis (axial SpA) continue to advance. Objectives: The objectives of this study were to compare referrals, diagnosis, and management of axial SpA in Western Europe (WE), North America (US and Canada), and the rest of world (RoW) in academic and community rheumatology practices and to identify areas for further education. Methods: Rheumatologists responded online to the MAXIMA (Management of Axial SpA International and Multicentric Approaches) survey. Questions pertained to referral, diagnosis, and management of axial SpA. Results: Rheumatologists (N = 809) from 56 countries completed the survey about patients with chronic back pain (>= 3 months) starting before age 45 years. Responses from academic and community practice rheumatologists were generally similar. Most referrals were from primary care providers. Symptom duration of 3 years or more at referral was reported more frequently by WE and RoW than US respondents. More WE and RoW than US rheumatologists referred to the Assessment of SpondyloArthritis International Society criteria for axial SpA in clinical practice. Rheumatologists reported prescribing disease-modifying antirheumatic drugs for the management of axial SpA. Sulfasalazine was frequently prescribed across regions; methotrexate was more commonly prescribed by US rheumatologists compared with other regions. Conclusions: Referral patterns, diagnosis, and disease management for axial SpA were similar among WE, North America, and RoW rheumatologists and in academic/community practices, although more WE and RoW rheumatologists referred to Assessment of SpondyloArthritis International Society criteria in clinical practice. Disease-modifying antirheumatic drugs were commonly prescribed for axial SpA patients, although it was unclear whether these were prescribed for axial or peripheral symptoms

Investigating diagnosis, treatment, and burden of disease in patients with ankylosing spondylitis in Central Eastern Europe and the United States: a real-world study.

INTRODUCTION/OBJECTIVES: Ankylosing spondylitis (AS) is a chronic inflammatory immune-mediated condition. We compared AS diagnosis, treatment, and burden in Central Eastern European countries (CEE), where this has been less researched, and the United States (US) from a real-world perspective. METHODS: Point-in-time survey of rheumatologists and their AS patients was conducted in the US (Apr-Oct 2018) and CEE (Aug-Nov 2019) via physician- and patient-completed record forms, including clinical and patient-reported outcomes. Statistical analysis included descriptive statistics, t-tests, Fisher's exact tests, and generalized linear models. RESULTS: In total, 487 patients were recruited from 88 rheumatologists in the US and 922 patients from 126 rheumatologists in CEE. Time from onset of symptoms to final AS diagnosis was longer in CEE than the US (4.2 vs 2.7 years, p < 0.05). At diagnosis, a greater use of conventional synthetic disease-modifying antirheumatic drugs (DMARDs) and injected steroids was reported in CEE vs the US (43.7% vs 27.6%, p < 0.05; 19.3% vs 8.7%, p < 0.05). 22.9% of US patients received a biologic DMARD at diagnosis vs 10% of CEE patients (p < 0.05). At current consultation, biologic DMARD use in CEE was lower vs the US (27.9% vs 71.0%, p < 0.05). CEE vs US patients had greater disease activity (mean Bath Ankylosing Spondylitis Disease Activity Index 4.2 vs 3.1, p < 0.05) and worse quality of life (QoL; mean Ankylosing Spondylitis Quality of Life Questionnaire score 6.2 vs 8.4, p < 0.05). CONCLUSIONS: AS patients in CEE vs the US faced slower diagnosis and worse access to biologics, disease activity, and QoL. Whether early access to biologics can improve symptoms, QoL, and daily activities in AS patients in CEE remains to be seen. Key Points • The study provided evidence on the real-world approach to the diagnosis, treatment, and burden of axSpA (axial spondyloarthritis) in CEE compared with the US. • The study reported patients in CEE experienced longer delays in diagnosis and poorer access to biologics than in the US. • This may have resulted in higher disease activity, greater levels of pain, and poorer outcomes, as reported by patients with axSpA in CEE