Poor prognostic factors in predicting abatacept response in a phase III randomized controlled trial in psoriatic arthritis

In ASTRAEA (NCT01860976), abatacept significantly increased American College of Rheumatology criteria 20% (ACR20) responses at Week 24 versus placebo in patients with psoriatic arthritis (PsA). This post hoc analysis explored relationships between prospectively identified baseline characteristics [poor prognostic factors (PPFs) ] and response to abatacept. Patients were randomized (1:1) to receive subcutaneous abatacept 125 mg weekly or placebo for 24 weeks; those without ≥ 20% improvement in joint counts at Week 16 switched to open-label abatacept. Potential predictors of ACR20 response were identified by treatment arm using multivariate analyses. Likelihood of ACR20 response to abatacept versus placebo was compared in univariate and multivariate analyses in subgroups stratified by the PPF, as defined by EULAR and/or GRAPPA treatment guidelines. Odds ratios (ORs) were generated using logistic regression to identify meaningful differences (OR cut-off: 1.2). 424 patients were randomized and treated (abatacept n = 213; placebo n = 211). In abatacept-treated patients, elevated C-reactive protein (CRP), high Disease Activity Score based on 28 joints (CRP), presence of dactylitis, and ≥ 3 joint erosions were identified as predictors of response (OR > 1.2). In placebo-treated patients, only dactylitis was a potential predictor of response. In the univariate analysis stratified by PPF, ACR20 response was more likely (OR > 1.2) with abatacept versus placebo in patients with baseline PPFs than in those without; multivariate analysis confirmed this finding. Response to abatacept versus placebo is more likely in patients with features indicative of high disease activity and progressive disease; these characteristics are recognized as PPFs in treatment guidelines for PsA

Risk of radiation-induced second malignant neoplasms from photon and proton radiotherapy in paediatric abdominal neuroblastoma

Background and Purpose: State-of-the-art radiotherapy modalities have the potential of reducing late effects of treatment in childhood cancer survivors. Our aim was to investigate the carcinogenic risk associated with 3D conformal (photon) radiation (3D-CRT), intensity modulated arc therapy (IMAT) and pencil beam scanning proton therapy (PBS-PT) in the treatment of paediatric abdominal neuroblastoma. Materials and Methods: The risk of radiation-induced second malignant neoplasm (SMN) was estimated using the concept of organ equivalent dose (OED) for eleven organs (lungs, rectum, colon, stomach, small intestine, liver, bladder, skin, central nervous system (CNS), bone, and soft tissues). The risk ratio (RR) between radiotherapy modalities and lifetime absolute risks (LAR) were reported for twenty abdominal neuroblastoma patients (median, 4y; range, 1-9y) historically treated with 3D-CRT that were also retrospectively replanned for IMAT and PBS-PT. Results: The risk of SMN due to primary radiation was reduced in PBS-PT against 3D-CRT and IMAT for most patients and organs. The RR across all organs ranged from 0.38 ± 0.22 (bladder) to 0.98 ± 0.04 (CNS) between PBS-PT and IMAT, and 0.12 ± 0.06 (rectum and bladder) to 1.06 ± 0.43 (bone) between PBS-PT and 3D-CRT. The LAR for most organs was within 0.01–1% (except the colon) with a cumulative risk of 21 ± 13%, 35 ± 14% and 35 ± 16% for PBS-PT, IMAT and 3D-CRT, respectively. Conclusions: PBS-PT was associated with the lowest risk of radiation-induced SMN compared to IMAT and 3D-CRT in abdominal neuroblastoma treatment. Other clinical endpoints and plan robustness should also be considered for optimal plan selection

Body mass index and treatment response to subcutaneous abatacept in patients with psoriatic arthritis: a

Objective: This Methods: In ASTRAEA, patients with active PsA were randomised (1:1) to receive blinded weekly SC abatacept 125 mg or placebo for 24 weeks. Treatment response at week 24 was assessed by the proportions of patients achieving American College of Rheumatology 20% improvement response, Disease Activity Score in 28 joints (DAS28 (C reactive protein (CRP))) ≤3.6 and Results: Of 212/213 and 210/211 patients with baseline BMI data in the abatacept and placebo groups, respectively, 15% and 19% were underweight/normal, 36% and 27% were overweight, and 49% and 54% were obese. After adjusting for baseline characteristics, there were no significant differences for any outcome measure at week 24 with abatacept in the overweight or obese versus underweight/normal subgroup. In the placebo group, patients in the obese versus underweight/normal subgroup were significantly less likely to achieve DAS28 (CRP) Conclusion: BMI does not impact clinical or radiographic response to SC abatacept in patients with PsA. Trial registration number: NCT01860976

Body mass index and treatment response to subcutaneous abatacept in patients with psoriatic arthritis: a post hoc analysis of a phase III trial

Objective: This post hoc analysis of the phase III Active PSoriaTic Arthritis RAndomizEd TriAl (ASTRAEA) evaluated the effect of baseline body mass index (BMI) on subsequent response to subcutaneous (SC) abatacept in patients with psoriatic arthritis (PsA). Methods: In ASTRAEA, patients with active PsA were randomised (1:1) to receive blinded weekly SC abatacept 125 mg or placebo for 24 weeks. Treatment response at week 24 was assessed by the proportions of patients achieving American College of Rheumatology 20% improvement response, Disease Activity Score in 28 joints (DAS28 (C reactive protein (CRP))) ≤3.6 and <2.6, Health Assessment Questionnaire-Disability Index reduction from baseline ≥0.35 and radiographic non-progression (defined as change from baseline ≤0 in PsA-modified total Sharp/van der Heijde score). Responses were stratified by baseline BMI (underweight/normal, <25 kg/m2; overweight, 25–30 kg/m2; obese, >30 kg/m2) and compared in univariate and multivariate models. Results: Of 212/213 and 210/211 patients with baseline BMI data in the abatacept and placebo groups, respectively, 15% and 19% were underweight/normal, 36% and 27% were overweight, and 49% and 54% were obese. After adjusting for baseline characteristics, there were no significant differences for any outcome measure at week 24 with abatacept in the overweight or obese versus underweight/normal subgroup. In the placebo group, patients in the obese versus underweight/normal subgroup were significantly less likely to achieve DAS28 (CRP) <2.6 at week 24 (OR 0.26; 95% CI 0.08 to 0.87; p=0.03). Conclusion: BMI does not impact clinical or radiographic response to SC abatacept in patients with PsA

A Search for Muon-neutrino to Electron-neutrino and Muon-antineutrino to Electron-antineutrino Oscillations at NuTeV

Limits on $\nu_\mu \to \nu_e$ and $\bar\nu_\mu \to \bar\nu_e$ oscillations are extracted using the NuTeV detector with sign-selected $\nu_\mu$ and \nub_\mu beams. In \nub_\mu mode, for the case of $\sin^2 2\alpha = 1$, $\Delta m^2 > 2.6$ ${\rm eV^2}$ is excluded, and for $\Delta m^2 \gg 1000$ ${\rm eV^2}$, $\sin^2 2\alpha > 1.1 \times 10^{-3}$. The NuTeV data exclude the high $\Delta m^2$ end of $\bar\nu_\mu \to \bar\nu_e$ oscillations parameters favored by the LSND experiment without the need to assume that the oscillation parameters for $\nu$ and \nub are the same. We present the most stringent experimental limits for $\nu_\mu (\bar{\nu}_\mu) \to \nu_e (\bar{\nu}_e)$ oscillations in the large $\Delta m^2$ region.Comment: 4 pages, 3 figures. Submitted to Phys. Rev. Letters, UR-164

Explicit asymptotic modelling of transient Love waves propagated along a thin coating

The official published version can be obtained from the link below.An explicit asymptotic model for transient Love waves is derived from the exact equations of anti-plane elasticity. The perturbation procedure relies upon the slow decay of low-frequency Love waves to approximate the displacement field in the substrate by a power series in the depth coordinate. When appropriate decay conditions are imposed on the series, one obtains a model equation governing the displacement at the interface between the coating and the substrate. Unusually, the model equation contains a term with a pseudo-differential operator. This result is confirmed and interpreted by analysing the exact solution obtained by integral transforms. The performance of the derived model is illustrated by numerical examples.This work is sponsored by the grant from Higher Education of Pakistan and by the Brunel University’s “BRIEF” research award

Building information modelling: A case study approach to identify readiness criteria for process requirement

Building Information Modelling (BIM) is defined as an approach to building design and construction through modeling technology, associated set of processes and people to produce, communicate and analyse building information models. Although the potential benefits of BIM are well documented, the implementation process requires a thoughtful review of many aspects to realise those benefits. Case study of BIM implementation is therefore important to be carried out to understand the BIM nature and the context of its implementation to which suits the local needs. The aim of this paper is therefore set to present the BIM implementation case study in which focus on BIM readiness criteria. It is important to note that, the term BIM readiness criteria used within this paper, refers to the BIM implementation requirement that focus on process element that takes place at the organisational level. Setting in the background of Malaysian construction industry the research engaged a multiple-case-studies approach and four design consultant companies were selected for the primary data collection. Data from each company were analysed by using content analysis technique. This paper, however presents one of the case studies that was conducted at Industrialised Building System (IBS) company. Three readiness criteria were identified and they are Policy, Implementation Management and Process Change Strategy

N-body Models of Rotating Globular Clusters

We have studied the dynamical evolution of rotating globular clusters with direct $N$-body models. Our initial models are rotating King models; we obtained results for both equal-mass systems and systems composed out of two mass components. Previous investigations using a Fokker-Planck solver have revealed that rotation has a noticeable influence on stellar systems like globular clusters, which evolve by two-body relaxation. In particular, it accelerates their dynamical evolution through the gravogyro instability. We have validated the occurence of the gravogyro instability with direct $N$-body models. In the case of systems composed out of two mass components, mass segregation takes place, which competes with the rotation in the acceleration of the core collapse. The "accelerating" effect of rotation has not been detected in our isolated two-mass $N$-body models. Last, but not least, we have looked at rotating $N$-body models in a tidal field within the tidal approximation. It turns out that rotation increases the escape rate significantly. A difference between retrograde and prograde rotating star clusters occurs with respect to the orbit of the star cluster around the Galaxy, which is due to the presence of a ``third integral'' and chaotic scattering, respectively.Comment: 16 pages, 17 figures, accepted by MNRA

Fabrication of low-cost, cementless femoral stem 316L stainless steel using investment casting technique

Total hip arthroplasty is a flourishing orthopedic surgery, generating billions of dollars of revenue. The cost associated with the fabrication of implants has been increasing year by year, and this phenomenon has burdened the patient with extra charges. Consequently, this study will focus on designing an accurate implant via implementing the reverse engineering of three-dimentional morphological study based on a particular population. By using finite element analysis, this study will assist to predict the outcome and could become a useful tool for preclinical testing of newly designed implants. A prototype is then fabricated using 316L stainless steel by applying investment casting techniques that reduce manufacturing cost without jeopardizing implant quality. The finite element analysis showed that the maximum von Mises stress was 66.88MPa approximately with a safety factor of 2.39 against endosteal fracture, and micromotion was 4.3um, which promotes osseointegration. This method offers a fabrication process of comentless femoral stems with lower cost, subsequently helping patients, particularly those from nondeveloped countries