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Mature overall survival (OS) data are often unavailable at the time of regulatory and reimbursement decisions for a new cancer treatment. For patients with early-stage cancers treated with potentially curative treatments, demonstrating an OS benefit may take years and may be confounded by subsequent lines of therapy or crossover to the investigational treatment. For patients with advanced-stage cancers, mature OS data may be available but difficult to interpret for similar reasons. There are strong opinions about approval and reimbursement in the absence of mature OS data, with concerns over delay in patient access set against concerns about uncertainty in long-term benefit. This position paper reflects our individual views as patient advocate, clinician or health economist on one aspect of this debate. We look at payer decisions in the absence of mature OS data, considering when and how non-OS trial outcomes could inform decision-making and how uncertainty can be addressed beyond the trial, supporting these views with evidence from the literature. We consider when it is reasonable for payers to expect or not expect mature OS data at the initial reimbursement decision (based on criteria such as cancer stage and treatment efficacy) acknowledging that there are settings in which mature OS data are expected. We propose flexible strategies for generating and appraising patient-relevant evidence, including context-relevant endpoints and quality of life measures, when survival rates are good and mature OS data are not expected. We note that fair reimbursement is important; this means valuing patient benefit as shown through prespecified endpoints and reappraising if there is ongoing uncertainty or failure to show a sustained benefit. We suggest that reimbursement systems continue to evolve to align with scientific advances, because innovation is only meaningful if readily accessible to patients. The proposed strategies have the potential to promote thorough assessment of potential benefit to patients and lead to timely access to effective medicines., Graphical Abstract

The continuous strive for increased sensitiv ity and higher resolution of space based telescopes can only be satisfied with larger primary mirrors. There are quite a few challenges in launching large mirrors in space such as surviving the stress created from the launch acceleration, deployment, thermoelastic deformations, the gravity release etc. Major constraint to space based application is weight which drives the development of thin, extremely lightweight mirrors. Such mirrors are prone for stress based deformations and need active optics correction chain (AOCC) in order to be operated at their full potential. An AOCC for large monolithic mirrors consists of three key active optics components: corrective element (e.g. deformable mirror or DM), wavefront sensor (WFS) and correction algorithm. In order to assess the feasibility of such a system we have developed an AOCC test stand in a collaboration with the European Space Agency (ESA) a nd Netherlands Organisation for Applied Scientific Research (TNO). With this development we aim to measure the performance and the long-term reliability of an AOCC in controlled laboratory conditions. Our design consists of two separate parts, one where the expected aberrations are generated and another where they are measured and corrected. Two deformable mirrors of 37.5 mm and 116 mm are used, the smallest mirror to generate aberrations and the largest to correct them. For wavefront sensing we are using two different wavefront sensors, an 11x11 Shack-Hartmann as well as phase diversity based at the science sensor. We are able to emulate the conditions for both, astronomy related, and Earth observations. Here, we present the design of the system, including the test stand and the correction algorithms, the performance expected from simulations, and the results from the latest lab tests.

The Dark Energy Survey Instrument (DESI) is a 5000-fibre optical multi object spectrograph for the 4m Mayall telecope at the Kitt Peak National Observatory. Ten identical three channel spectrographs will be equipped with 500-element fibre slits. Here we focus on the architecture of the science slits and the interchangeable auxiliary slits required for calibration.

An astronomical adaptive optics test-bench, designed to replicate the conditions of a 4 m-class telescope, is presented. Named DRAGON-Next Generation, it is constructed primarily from commercial off-the-shelf components with minimal customization (approximately a 90:10 ratio). This permits an optical design which is modular and this leads to a reconfigurability. DRAGON-NG has been designed for operation for the following modes: (high-order) SCAO, (twin-DM) MOAO, and (twin-DM) MCAO. It is capable of open-loop or closed-loop operation, with (3) natural and (3) laser guide-star emulation at loop rates of up to 200Hz. Field angles of up-to 2.4 arcmin (4m pupil emulation) can pass through the system. The design is dioptric and permits long cable runs to a compact real-time control system which is on-sky compatible. Therefore experimental validation can be carried out on DRAGON-NG before transferring to an on-sky system, which is a significant risk mitigation.

Recent advances in adaptive optics (AO) have led to the implementation of wide field-of-view AO systems. A number of wide-field AO systems are also planned for the forthcoming Extremely Large Telescopes. Such systems have multiple wavefront sensors of different types, and usually multiple deformable mirrors (DMs). Here, we report on our experience integrating cameras and DMs with the real-time control systems of two wide-field AO systems. These are CANARY, which has been operating on-sky since 2010, and DRAGON, which is a laboratory adaptive optics real-time demonstrator instrument. We detail the issues and difficulties that arose, along with the solutions we developed. We also provide recommendations for consideration when developing future wide-field AO systems., Accepted for publication in MNRAS

We describe the fiber system of the Dark Energy Spectroscopic Instrument (DESI). Its primary science goal is to provide a survey of 14,000 square degrees of the extragalactic sky using the Mayall 4m telescope in five years. The fibre system will provide a multiplex gain of 5000 so that more than 20 million galaxies can surveyed. Applying a number of tests to the survey dataset should allow the evolution of the equation of state of the universe to be determined to greater accuracy than before. The fibre system will provide a multiplex gain of 5000 with very high levels of performance.

The Multi-Aperture Real Time Image Normalisation Instrument (MARTINI) is an adaptive optics system designed to operate at one of the Nasmyth focal stations of the 4.2 m William Herschel Telescope. Correction of atmospherically distorted images is achieved by the action of a six element segmented mirror in a real-time servo loop controlled by the signal from a CCD based Shack–Hartmann wavefront sensor. A unique aspect of the MARTINI instrument is that, from its conception, it was designed to be capable of image sharpening at visible wavelengths. An outline of the mechanical and electronic arrangement of MARTINI is given, together with a description of its modes of operation, facilities and performance. Also described are some of the first scientific results obtained with the instrument.

International audience; Context. A new challenging adaptive optics (AO) system, called multi-object adaptive optics (MOAO), has been successfully demonstrated on-sky for the first time at the 4.2 m William Herschel Telescope, Canary Islands, Spain, at the end of September 2010. Aims: This system, called CANARY, is aimed at demonstrating the feasibility of MOAO in preparation of a future multi-object near infra-red (IR) integral field unit spectrograph to equip extremely large telescopes for analysing the morphology and dynamics of high-z galaxies. Methods: CANARY compensates for the atmospheric turbulence with a deformable mirror driven in open-loop and controlled through a tomographic reconstruction by three widely separated off-axis natural guide star (NGS) wavefront sensors, which are in open loop too. We compared the performance of conventional closed-loop AO, MOAO, and ground-layer adaptive optics (GLAO) by analysing both IR images and simultaneous wave-front measurements. Results: In H-band, Strehl ratios of 0.20 are measured with MOAO while achieving 0.25 with closed-loop AO in fairly similar seeing conditions (r0 ≈ 15 cm at 0.5 mum). As expected, MOAO has performed at an intermediate level between GLAO and closed-loop AO.

International audience; The CANARY on-sky MOAO demonstrator is being integrated in the laboratory and a status update about its various components is presented here. We also discuss the alignment and calibration procedures used to improve system performance and overall stability. CANARY will be commissioned at the William Herschel Telescope at the end of September 2010.

CANARY is the on-sky LGS MOAO demonstrator for the proposed EAGLE E-ELT instrument. The CANARY design is described here for the initial experimental phases. Simulations of system performance predict an H-band Strehl ratio of 0.27-0.33.

SLODAR (slope detection and ranging) is a technique we have developed to monitor the vertical profile of atmospheric phase distortions, for application to astronomical adaptive optics systems. The technique uses the correlation between slope measurements made using a Shack-Hartmann wavefront sensor observing a binary star. In this paper we describe the principle of SLODAR and then describe our work on using a system for the measurement of horizontal turbulence profiles for application to free space optical communications. This work has also been presented elsewhere1

SLODAR (slope detection and ranging) is a technique we have developed to monitor the vertical profile of atmospheric phase distortions, for application to astronomical adaptive optics systems. The technique uses the correlation between slope measurements made using a Shack-Hartmann wavefront sensor observing a binary star. In this paper we describe the principle of SLODAR and then describe our work on using a system for the measurement of horizontal turbulence profiles for application to free space optical communications.

A dual layer laboratory multiconjugate adaptive optics system is presented. The system emulates 5 guide stars propagating through dual layer turbulence, and their correction by two wavefront correctors. Initial results from this system are presented.

An experimental Ground Layer Adaptive Optics system utilizing a low-altitude Rayleigh Laser Guide Star is presented. This demonstrator is designed for the GHRIL Nasmyth platform of the 4.2m William Herschel Telescope, where it uses a low-altitude (~4km) focused-spot 523nm Rayleigh-scatter beacon, launched from behind the secondary mirror using an independent beam launch telescope. A novel range-gate is used to select the LGS return altitude for wavefront sensing, whilst wavefront correction uses a 97-actuator continuous phase sheet deformable mirror and separate tip-tilt mirror. The performance can be monitored on-axis and off-axis. These and other aspects of the demonstration system are described in detail, including optical design, laser launch technique, laboratory performance, and a preliminary assessment of potential on-sky performance.

VISTA is a 4-metre survey telescope currently being constructed on the NTT peak of ESO’s Cerro Paranal Observatory. The telescope will be equipped with a dedicated infrared camera providing images of a 1.65 degree field of view. The telescope and camera are of an innovative f/3.26 design with no intermediate focus and no cold stop. The mosaic of 16 IR detectors is located directly at Cassegrain focus and a novel baffle arrangement is used to suppress stray light within the cryostat. The pointing and alignment of the telescope and camera is monitored by wavefront sensing elements within the camera cryostat itself. This paper describes the optical, mechanical, electronic and thermal design of the combined curvature sensor and auto-guider units positioned at the periphery of the camera field of view. Centroid and image aberration data is provided to the telescope control system allowing real time correction of pointing and alignment of the actively positioned M2 unit. Also described are the custom optics, mounted in the camera filter wheel, which are used to perform near on-axis high order curvature sensing. Analysis of the corresponding defocused images allows calibration tables of M1 actuator positions to be constructed for varying telescope declination and temperature.

We describe the initial results of a laboratory experiment designed to emulate the performance of a multiconjugate adaptive optics (MCAO) system based on dual layer turbulence and dual layer correction.

NAOMI (Nasmyth Adaptive Optics for Multi-purpose Instrumentation) is a recently completed and commissioned astronomical facility on the 4.2m William Herschel Telescope. The system is designed to work initially with Natural Guide Stars and also to be upgradeable for use with a single laser guide star. It has been designed to work with both near infrared and optical instrumentation (both imagers and spectrographs). The system uses a linearised segmented adaptive mirror and dual-CCD Shack-Hartmann wavefront sensor together with a multiple-DSP real-time processing system. Control system parameters can be updated on-the-fly by monitoring processes and the system can self-optimize its base optical figure to compensate for the optical characteristics of attached scientific instrumentation. The scientific motivation, consequent specification and implementation of NAOMI are described, together with example performance data and information on future upgrades and instrumentation.

Conventional adaptive optics systems using a single wavefront corrector suffer from a limited field of view. Multi-conjugate adaptive optics use two or more corrector to improve off-axis correction. We describe an experimental system which simulates dual-layer turbulence, and present results using a single corrector showing anisoplanatic effects. Future experiments using a second corrector are also discussed.

Liquid crystal spatial light modulators have recently been used to generate aberrated wavefronts. We have used two ferroelectric liquid crystal devices to simulate turbulence from two layers of the atmosphere, which will be used in future work to test multi-conjugate adaptive optics systems.© (1999) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

ELECTRA is the University of Durham's high order AO system designed for the William Herschel Telescope. The correcting element is a segmented deformable mirror, where each segment is driven by a cylindrical piezoelectric actuator such that it can be moved in tip, tilt and piston. In order to cophase all the segments of the mirror it is necessary to calibrate and linearize the response of these actuators. To this end, we have installed strain gauge transducers along the electrodes of each actuator to provide information on their instantaneous extensions and calibrated their responses.

An astronomical AO system for use on a 4 m class telescope at visible wavelengths is described. The design of this instrument is based on the University of Durham semi common-user partial-AO system MARTINI. A brief technical resume and recent astronomical results are provided. The MARTINI system was designed on a partial, but non-modal, philosophy which is able to deliver modest image improvements normally associated with low order corrections at small D/ro. The new system will remove the limited aperture coverage of the MARTINI system and extend its operating philosophy to produce a corrected optical transfer function optimized to scientific goals. The requirements and resulting system design are described. The system is also designed to be accommodated within the general scheme of the UK national AO program which was initiated in 1993. A brief discussion of the design issues involved is provided.© (1994) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

As applied to the 4.2-m William Herschel Telescope, the multiaperture real-time image-normalization system presented implies a wavefront whose size requires a mask of six optimally-scaled subapertures. These subaperture images are separated and examined on a single image photon detector which yields x, y, and t coordinates for each recorded photon. The motions of these images feed back to six independent piezoactuated active mirrors which act to null the image motions at a CCD focus. Data are presented from two image normalization runs, with and without active mirrors, which illustrate the size and variation behavior of the coherent seeing length, characteristic seeing times, and power spectra.© (1990) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

We present the results from a laboratory multiconjugate adaptive optics experiment. The experiment is differentiated from other published work in that it has a programmable deterministic turbulence generator and an output science camera. The turbulence was generated using a dual layer turbulence emulator, and then corrected using an AO system with 2 wavefront correctors and a Shack-Hartman wavefront sensor, which processed information from five artificial guide stars. We report our results and also describe some of the problems.

We describe a binary approach to adaptive wave-front correction, especially suitable for narrow band applications, which would be simpler than conventional adaptive technology. Appropriate parts of the aberrant wave front are phase retarded by half a wavelength to ensure that none of the image-forming rays add together destructively. Simulations for monochromatic light show that the residual wave-front errors, in the absence of other errors, would result in Strehl ratios of ~40% with diffraction-limited widths at visible wavelengths. We simulate the imaging performance of such a system and describe a possible implementation that uses a ferroelectric liquid-crystal spatial light modulator.

Description d'un interferometre a dedoublement de front d'onde utilise pour la mesure de la fonction de transfert de modulation atmospherique

Calculations have been made of the intensity distribution of star images formed at the focal surface of large Schmidt telescopes. The calculations take account of atmaspheric seeing, aperture diffraction, manufacturing errors, chromatic errors in the corrector plate, scattering in the emulsion, photographic response and grain structure. The results are expressed in terms of simulated microdensitometer scans across the processed emulsion.

We present the first on-sky results of CANARY, the multi-object adaptive optics demonstrator of EAGLE.

We present results of the isoplanatic performance of an astronomical adaptive optics system in the laboratory, by using a dual layer turbulence simulator. We describe how the performance of adaptive correction degrades with off--axis angle. These experiments demonstrate that it is now possible to produce quantifiable multi-layer turbulence in the laboratory as a precursor to constructing multi-conjugate adaptive optics.

The Multiple Aperture Real Time Image Normalization Instrument (MARTINI) is an astronomical adaptive optics system for visible imaging and spectroscopic feedthrough at the 4.2-m William Herschel Telescope on La Palma. It consists of a six-subaperture, tip-tilt-piston, segmented mirror device and uses 4r(0) aperture-matching to provide optimum slope removal in zones large enough for operation in the visible and with reference objects fainter than V = 13 exp m. This limit is achieved by optimizing the use of reference light, by analyzing the information from a photon counting wavefront sensor using a non-flaming (i.e., irregular sampling) infinite impulse response filter for estimation and prediction of the wavefront slopes. The value of this approach is discussed along with its extension to higher-order correction schemes. Experimental evidence supporting the theoretical basis of the MARTINI system is also presented. The astronomical potential of such an approach, and the drawbacks, are outlined.