Efficacy of tofacitinib monotherapy in methotrexate-naive patients with early or established rheumatoid arthritis.

IntroductionTofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib monotherapy was previously shown to inhibit structural damage, reduce clinical signs and symptoms of RA, and improve physical functioning over 24 months in methotrexate (MTX)-naive adult patients with RA. In this post hoc analysis, we compared efficacy and safety of tofacitinib in patients with early (disease duration <1 year) versus established (≥1 year) RA.MethodsMTX-naive patients ≥18 years with active RA received tofacitinib monotherapy (5 or 10 mg two times a day, or MTX monotherapy, in a 24-month Phase 3 trial.ResultsOf 956 patients (tofacitinib 5 mg two times a day, n=373; tofacitinib 10 mg two times a day, n=397; MTX, n=186), 54% had early RA. Baseline disease activity and functional disability were similar in both groups; radiographic damage was greater in patients with established RA. At month 24, clinical response rates were significantly greater in patients with early versus established RA in the tofacitinib 5 mg two times a day group. Both tofacitinib doses had greater effects on clinical, functional and radiographic improvements at 1 and 2 years compared with MTX, independent of disease duration. No new safety signals were observed.ConclusionsTreatment response was generally similar in early and established RA; significantly greater improvements were observed at month 24 with tofacitinib 5 mg two times a day in early versus established RA. Tofacitinib 5 and 10 mg two times a day demonstrated greater efficacy versus MTX irrespective of disease duration. No difference in safety profiles was observed between patients with early or established RA.Trial registration numberNCT01039688; Results

Towards a Conceptualization of Sociomaterial Entanglement

In knowledge representation, socio-technical systems can be modeled as multiagent systems in which the local knowledge of each individual agent can be seen as a context. In this paper we propose formal ontologies as a means to describe the assumptions driving the construction of contexts as local theories and to enable interoperability among them. In particular, we present two alternative conceptualizations of the notion of sociomateriality (and entanglement), which is central in the recent debates on socio-technical systems in the social sciences, namely critical and agential realism. We thus start by providing a model of entanglement according to the critical realist view, representing it as a property of objects that are essentially dependent on different modules of an already given ontology. We refine then our treatment by proposing a taxonomy of sociomaterial entanglements that distinguishes between ontological and epistemological entanglement. In the final section, we discuss the second perspective, which is more challenging form the point of view of knowledge representation, and we show that the very distinction of information into modules can be at least in principle built out of the assumption of an entangled reality

Evolution of additional (hidden) quantum variables in the interference of Bose-Einstein condensates

Additional variables (also often called “hidden variables”) are sometimes added to standard quantum mechanics in order to remove its indeterminism or “incompleteness” and to make the measurement process look more classical. Here we discuss a case in which an additional variable arises almost spontaneously from the quantum formalism: the emergence of a relative phase between two highly populated Fock-state Bose-Einstein condensates. The model simulated here involves the interference of two Bose condensates, one with all up spins and the other with down spins, along a z axis. With the clouds overlapping, we consider the results of measuring spins in a transverse plane (the general direction is studied in an appendix). The determination of the previously “hidden” phase becomes progressively more definite as additional measurements are made. We also provide an analysis of a recent and closely related experiment

Elicitation of expert knowledge to inform object-based audio rendering to different systems

Object-based audio presents the opportunity to optimise audio reproduction for different listening scenarios. Vector base amplitude panning (VBAP) is typically used to render object-based scenes. Optimizing this process based on knowledge of the perception and practices of experts could result in significant improvements to the end user's listening experience. An experiment was conducted to investigate how content creators perceive changes in the perceptual attributes of the same content rendered to systems with different numbers of channels, and to determine what they would do differently to standard VBAP and matrix based downmixes to minimize these changes. Text mining and clustering of the content creators' responses revealed 6 general mix processes: the spatial spread of individual objects, EQ and processing, reverberation, position, bass, and level. Logistic regression models show the relationships between the mix processes, perceived changes in perceptual attributes, and the rendering method/speaker layout. The relative frequency of use for the different mix processes was found to differ between categories of audio object suggesting that any downmix rules should be object category specific. These results give insight into how object-based audio can be used to improve listener experience and provide the first template for doing this across different reproduction systems

SIMULATION AND MODELLING OF RAID 0 SYSTEM PERFORMANCE

RAID systems are fundamental components of modern storage infrastructures. It is therefore important to model their performance effectively. This paper describes a simulation model which predicts the cumulative distribution function of I/O request response time in a RAID 0 system consisting of homogeneous zoned disk drives. The model is constructed in a bottom-up manner, starting by abstracting a single disk drive as an M/G/1 queue. This is then extended to model a RAID 0 system using a split-merge queueing network. Simulation results of I/O request response time for RAID 0 systems with various numbers of disks are computed and compared against device measurements

Why not be Versatile? Applications of the SGNMT Decoder for Machine Translation

SGNMT is a decoding platform for machine translation which allows paring various modern neural models of translation with different kinds of constraints and symbolic models. In this paper, we describe three use cases in which SGNMT is currently playing an active role: (1) teaching as SGNMT is being used for course work and student theses in the MPhil in Machine Learning, Speech and Language Technology at the University of Cambridge, (2) research as most of the research work of the Cambridge MT group is based on SGNMT, and (3) technology transfer as we show how SGNMT is helping to transfer research findings from the laboratory to the industry, eg. into a product of SDL plc

Deformation of lamellar TiAl alloys by longitudinal twinning

© 2016 Elsevier Ltd. The occurrence of longitudinal twinning in the engineering alloy Ti-45Al-2Nb-2Mn (at.%)-0.8 vol.% TiB2 has been studied by measuring the changes in crystallographic orientation within individual lamellae during microcompression. Twinning in this alloy appeared to be a nucleation-limited process with the twins growing from lamellar boundaries at resolved shear stresses as low as 100 MPa, consistent with observations elsewhere. However, instead of forming twins ∼ 10-200 nm in thickness, as in polysynthetically twinned crystals, the longitudinal twins in this alloy were initiated at a lamellar boundary and then spread through the whole lamella.The work was supported by the EPSRC / Rolls-Royce Strategic Partnership (EP/H500375/1). Alberto Palomares Garcia, Claire Davis and Robert Jones are acknowledged for discussions and help with the TEM respectively

Source sentence simplification for statistical machine translation

Long sentences with complex syntax and long-distance dependencies pose difficulties for machine translation systems. Short sentences, on the other hand, are usually easier to translate. We study the potential of addressing this mismatch using text simplifi- cation: given a simplified version of the full input sentence, can we use it in addition to the full input to improve translation? We show that the spaces of original and simplified translations can be effectively combined using translation lattices and compare two decoding approaches to process both inputs at different levels of integration. We demonstrate on source-annotated portions of WMT test sets and on top of strong baseline systems combining hierarchical and neural translation for two language pairs that source simplification can help to improve translation quality.This work was supported by the EPSRC grant Improving Target Language Fluency in Statistical Machine Translation, grant number EP/L027623/1