Secukinumab demonstrated sustained retention, effectiveness and safety in a real-world setting in patients with moderate-to-severe plaque psoriasis: long-term results from an interim analysis of the SERENA study.

Randomized controlled trials of secukinumab have shown sustained efficacy and a favourable safety profile in multiple manifestations of psoriatic disease. To assess the long-term, real-world retention, effectiveness and safety of secukinumab in routine clinical practice for the treatment of moderate-to-severe plaque-type psoriasis (PsO). SERENA (CAIN457A3403) is a large, ongoing, longitudinal, observational study conducted at 438 sites and 19 countries for an expected duration of up to 5 years in adult patients with moderate-to-severe PsO, psoriatic arthritis and ankylosing spondylitis. Patients received ≥16 weeks of secukinumab treatment before enrolment. This interim analysis presents data from PsO patients, who were enrolled in the study between October-2016 and October-2018 and were observed for ≥2 years. In total, 1756 patients (67.3% male) with a mean age of 48.4 years and body mass index of 28.8 kg/m <sup>2</sup> were included in the analysis. The secukinumab treatment retention rates after 1, 2 and 3 years in the study were 88.0%, 76.4% and 60.5%, respectively. Of the 648 patients who discontinued the study, the most common reasons included lack of efficacy (42.6%), adverse event (17.4%), physician decision (12.2%) and subject decision (11.6%). Mean ± SD absolute PASI was 21.0 ± 13.0 at the start of treatment (n = 1,564). At baseline, the mean ± SD PASI score reduced to 2.6 ± 4.8 and remained low at Year 1 (2.3 ± 4.3), Year 2 (1.9 ± 3.6) and Year 3 (1.9 ± 3.5). The safety profile of secukinumab during the SERENA study was consistent with its known safety profile, with no new safety signals reported. Particularly, low rates of inflammatory bowel disease (0.3%; Incidence Rate [IR]:0.15), candida infections (3.1%; IR:1.43) and MACE (0.9%; IR:0.37) were observed. Secukinumab showed high treatment persistence, sustained effectiveness and a favourable safety profile up to 3 years of follow-up in the real-world population of PsO patients observed in SERENA

The camera of the fifth H.E.S.S. telescope. Part I: System description

In July 2012, as the four ground-based gamma-ray telescopes of the H.E.S.S. (High Energy Stereoscopic System) array reached their tenth year of operation in Khomas Highlands, Namibia, a fifth telescope took its first data as part of the system. This new Cherenkov detector, comprising a 614.5 m^2 reflector with a highly pixelized camera in its focal plane, improves the sensitivity of the current array by a factor two and extends its energy domain down to a few tens of GeV. The present part I of the paper gives a detailed description of the fifth H.E.S.S. telescope's camera, presenting the details of both the hardware and the software, emphasizing the main improvements as compared to previous H.E.S.S. camera technology.Comment: 16 pages, 13 figures, accepted for publication in NIM

Reconstructing initial data using observers: error analysis of the semi-discrete and fully discrete approximations

A new iterative algorithm for solving initial data inverse problems from partial observations has been recently proposed in Ramdani et al. (Automatica 46(10), 1616-1625, 2010 ). Based on the concept of observers (also called Luenberger observers), this algorithm covers a large class of abstract evolution PDE's. In this paper, we are concerned with the convergence analysis of this algorithm. More precisely, we provide a complete numerical analysis for semi-discrete (in space) and fully discrete approximations derived using finite elements in space and an implicit Euler method in time. The analysis is carried out for abstract Schrödinger and wave conservative systems with bounded observation (locally distributed)

On multigraded generalizations of Kirillov-Reshetikhin modules

We study the category of Z^l-graded modules with finite-dimensional graded pieces for certain Z+^l-graded Lie algebras. We also consider certain Serre subcategories with finitely many isomorphism classes of simple objects. We construct projective resolutions for the simple modules in these categories and compute the Ext groups between simple modules. We show that the projective covers of the simple modules in these Serre subcategories can be regarded as multigraded generalizations of Kirillov-Reshetikhin modules and give a recursive formula for computing their graded characters

Shape-induced force fields in optical trapping

Advances in optical tweezers, coupled with the proliferation of two-photon polymerization systems, mean that it is now becoming routine to fabricate and trap non-spherical particles. The shaping of both light beams and particles allows fine control over the flow of momentum from the optical to mechanical regimes. However, understanding and predicting the behaviour of such systems is highly complex in comparison with the traditional optically trapped microsphere. In this Article, we present a conceptually new and simple approach based on the nature of the optical force density. We illustrate the method through the design and fabrication of a shaped particle capable of acting as a passive force clamp, and we demonstrate its use as an optically trapped probe for imaging surface topography. Further applications of the design rules highlighted here may lead to new sensors for probing biomolecule mechanics, as well as to the development of optically actuated micromachines

Network Discovery Pipeline Elucidates Conserved Time-of-Day–Specific cis-Regulatory Modules

Correct daily phasing of transcription confers an adaptive advantage to almost all organisms, including higher plants. In this study, we describe a hypothesis-driven network discovery pipeline that identifies biologically relevant patterns in genome-scale data. To demonstrate its utility, we analyzed a comprehensive matrix of time courses interrogating the nuclear transcriptome of Arabidopsis thaliana plants grown under different thermocycles, photocycles, and circadian conditions. We show that 89% of Arabidopsis transcripts cycle in at least one condition and that most genes have peak expression at a particular time of day, which shifts depending on the environment. Thermocycles alone can drive at least half of all transcripts critical for synchronizing internal processes such as cell cycle and protein synthesis. We identified at least three distinct transcription modules controlling phase-specific expression, including a new midnight specific module, PBX/TBX/SBX. We validated the network discovery pipeline, as well as the midnight specific module, by demonstrating that the PBX element was sufficient to drive diurnal and circadian condition-dependent expression. Moreover, we show that the three transcription modules are conserved across Arabidopsis, poplar, and rice. These results confirm the complex interplay between thermocycles, photocycles, and the circadian clock on the daily transcription program, and provide a comprehensive view of the conserved genomic targets for a transcriptional network key to successful adaptation

Quantum noise in the position measurement of a cavity mirror undergoing Brownian motion

We perform a quantum theoretical calculation of the noise power spectrum for a phase measurement of the light output from a coherently driven optical cavity with a freely moving rear mirror. We examine how the noise resulting from the quantum back action appears among the various contributions from other noise sources. We do not assume an ideal (homodyne) phase measurement, but rather consider phase modulation detection, which we show has a different shot noise level. We also take into account the effects of thermal damping of the mirror, losses within the cavity, and classical laser noise. We relate our theoretical results to experimental parameters, so as to make direct comparisons with current experiments simple. We also show that in this situation, the standard Brownian motion master equation is inadequate for describing the thermal damping of the mirror, as it produces a spurious term in the steady-state phase fluctuation spectrum. The corrected Brownian motion master equation [L. Diosi, Europhys. Lett. {\bf 22}, 1 (1993)] rectifies this inadequacy.Comment: 12 pages revtex, 2 figure

Recovering the observable part of the initial data of an infinite-dimensional linear system with skew-adjoint generator

We consider the problem of recovering the initial data (or initial state) of infinite-dimensional linear systems with unitary semigroups. It is well-known that this inverse problem is well posed if the system is exactly observable, but this assumption may be very restrictive in some applications. In this paper we are interested in systems which are not exactly observable, and in particular, where we cannot expect a full reconstruction. We propose to use the algorithm studied by Ramdani et al. in (Automatica 46:1616–1625, 2010) and prove that it always converges towards the observable part of the initial state. We give necessary and sufficient condition to have an exponential rate of convergence. Numerical simulations are presented to illustratethe theoretical results

Prototype ATLAS IBL Modules using the FE-I4A Front-End Readout Chip

The ATLAS Collaboration will upgrade its semiconductor pixel tracking detector with a new Insertable B-layer (IBL) between the existing pixel detector and the vacuum pipe of the Large Hadron Collider. The extreme operating conditions at this location have necessitated the development of new radiation hard pixel sensor technologies and a new front-end readout chip, called the FE-I4. Planar pixel sensors and 3D pixel sensors have been investigated to equip this new pixel layer, and prototype modules using the FE-I4A have been fabricated and characterized using 120 GeV pions at the CERN SPS and 4 GeV positrons at DESY, before and after module irradiation. Beam test results are presented, including charge collection efficiency, tracking efficiency and charge sharing.Comment: 45 pages, 30 figures, submitted to JINS

Reconceptualizing CSR in the media industry as relational accountability

In this paper, we reconceptualize CSR in the media industries by combining empirical data with theoretical perspectives emerging from the communication studies and business ethics literature. We develop a new conception of what corporate responsibility in media organizations may mean in real terms by bringing Bardoel and d’Haenens’ (European Journal of Communication 19 165–194 2004) discussion of the different dimensions of media accountability into conversation with the empirical results from three international focus group studies, conducted in France, the USA and South Africa. To enable a critical perspective on our findings, we perform a philosophical analysis of its implications for professional, public, market, and political accountability in the media, drawing on the insights of Paul Virilio. We come to the conclusion that though some serious challenges to media accountability exist, the battle for responsible media industries is not lost. In fact, the speed characterizing the contemporary media environment may hold some promise for fostering the kind of relational accountability that could underpin a new understanding of CSR in the media