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Background: Pembrolizumab is active in head and neck squamous cell carcinoma (HNSCC), with programmed cell death ligand 1 (PD-L1) expression associated with improved response. Methods: KEYNOTE-048 was a randomised, phase 3 study of participants with untreated locally incurable recurrent or metastatic HNSCC done at 200 sites in 37 countries. Participants were stratified by PD-L1 expression, p16 status, and performance status and randomly allocated (1:1:1) to pembrolizumab alone, pembrolizumab plus a platinum and 5-fluorouracil (pembrolizumab with chemotherapy), or cetuximab plus a platinum and 5-fluorouracil (cetuximab with chemotherapy). Investigators and participants were aware of treatment assignment. Investigators, participants, and representatives of the sponsor were masked to the PD-L1 combined positive score (CPS) results; PD-L1 positivity was not required for study entry. The primary endpoints were overall survival (time from randomisation to death from any cause) and progression-free survival (time from randomisation to radiographically confirmed disease progression or death from any cause, whichever came first) in the intention-to-treat population (all participants randomly allocated to a treatment group). There were 14 primary hypotheses: superiority of pembrolizumab alone and of pembrolizumab with chemotherapy versus cetuximab with chemotherapy for overall survival and progression-free survival in the PD-L1 CPS of 20 or more, CPS of 1 or more, and total populations and non-inferiority (non-inferiority margin: 1·2) of pembrolizumab alone and pembrolizumab with chemotherapy versus cetuximab with chemotherapy for overall survival in the total population. The definitive findings for each hypothesis were obtained when statistical testing was completed for that hypothesis; this occurred at the second interim analysis for 11 hypotheses and at final analysis for three hypotheses. Safety was assessed in the as-treated population (all participants who received at least one dose of allocated treatment). This study is registered at ClinicalTrials.gov, number NCT02358031. Findings: Between April 20, 2015, and Jan 17, 2017, 882 participants were allocated to receive pembrolizumab alone (n=301), pembrolizumab with chemotherapy (n=281), or cetuximab with chemotherapy (n=300); of these, 754 (85%) had CPS of 1 or more and 381 (43%) had CPS of 20 or more. At the second interim analysis, pembrolizumab alone improved overall survival versus cetuximab with chemotherapy in the CPS of 20 or more population (median 14·9 months vs 10·7 months, hazard ratio [HR] 0·61 [95% CI 0·45–0·83], p=0·0007) and CPS of 1 or more population (12·3 vs 10·3, 0·78 [0·64–0·96], p=0·0086) and was non-inferior in the total population (11·6 vs 10·7, 0·85 [0·71–1·03]). Pembrolizumab with chemotherapy improved overall survival versus cetuximab with chemotherapy in the total population (13·0 months vs 10·7 months, HR 0·77 [95% CI 0·63–0·93], p=0·0034) at the second interim analysis and in the CPS of 20 or more population (14·7 vs 11·0, 0·60 [0·45–0·82], p=0·0004) and CPS of 1 or more population (13·6 vs 10·4, 0·65 [0·53–0·80], p

The LHC will be composed of 1232 horizontally curved, 15-meter long, superconducting dipole assemblies and 474 Short Straight Sections containing various types of quadrupoles. These magnets are manufactured by several European companies and half of them are currently produced. The field quality at room temperature is strictly monitored to guide and validate the assembly at different stages of the production in the industry. Dipoles and quadrupoles are measured with two different rotating coil systems. These â€ﾜmoles” travel inside the 50 mm aperture and accurately measure the field and gradient strength integrated over the length, the field direction and high order harmonics. We describe here these two systems, their performance and the experience gained through the two first years of operation.

The LHC cryodipoles are composed of an evacuated cryostat and a cold mass, which is cooled by superfluid helium at 1.9 K. To obey constraints imposed by beam dynamics the particle beams must be centered within the mechanical axis of the dipole with a sub-millimeter accuracy. This requires in turn that the relative displacements between the cryostat and the cold mass must be monitored with accuracy at all times. Because of the extreme environmental conditions (the displacement must be measured in vacuum and between two points at a temperature difference of about 300 degrees), no adequate existing monitoring system was found for this application. We describe here a novel optical sensor developed for our scope and we present results of measurements made during the cold test of the dipoles.

In the superconducting main magnets of the Large Hadron Collider (LHC), persistent currents in the superconductor determine the field quality at injection field. For this reason it is necessary to check the magnetization of the cable strands during their production. During four gears, this requires measurements of the width of the strand magnetization hysteresis loop at 0.5 T, 1.9 K, at a rate of up to eight samples per day. This paper describes the design, construction and the first results of a magnetization test station built for this purpose. The samples are cooled in a cryostat, with a 2-m long elliptic tail. This tail is inserted in a normal conducting dipole magnet with a field between /spl plusmn/1.5 T. Racetrack pick-up coils, integrated in the cryostat, detect the voltage due to flux change, which is then integrated numerically. The sample holder can contain eight strand samples, each 20 cm long. The test station operates in two modes: either the sample is fixed while the external field is changed, or the sample is moved while the field remains constant, First results of calibration measurements with nickel and niobium are reported.

This paper reports on the magnetic field mapping performed on the HRS spectrometers of Hall A, which are of QQDQ type. The dipoles were measured with a set of Hall probes in the symmetry mid-plane. The quadrupoles were measured inside their whole volume by a set of axially segmented rotating coils. High accuracy has been reached in both cases. Dipoles and quadrupoles were measured for a set of excitation currents covering the operating momentum range of the HRS: 0.5–4 GeV/c. The main results on field determination are presented.

Performs acceptance tests including field measurements of the collared coils assembly of the LHC superconducting dipoles to estimate, at an early production stage, the possible significant deviations from the expected multipole component value of these magnets. A sensitive measuring probe and efficient data acquisition are the consequence of a low magnetizing current necessary to limit the coil heating. This demands a high signal sensitivity and an enhanced signal-to-noise ratio to retrieve the higher multipole component. Moreover, the correlation with the multipole content of the magnets at cryogenic temperature and nominal excitation current need to be identified before the manufacturing process may continue. The field probe of the mole-type is equipped with three radial rotating search coils, an angular encoder and gravity sensor. It has been designed to slide inside the bore of the dipole coils and to measure the local field at fixed positions. The field analysis resulting in terms of multipole components, field direction and field integrals, measured on four 10 m long, twin-aperture LHC dipole prototypes, will be described together with the performance of the measuring method.

This report summarizes the procedure for providing the absolute energy calibration of the LEP beams during the energy scan in 1993. The average beam energy around the LEP ring was measured in 25 calibrations with the resonant depolarization technique. The time variation of this average beam energy is well described by a model of the accelerator based on monitored quantities. The absolute calibration of the centre of mass energies of the off-peak points is determined with a precision of 2 parts in 10(5) resulting in a systematic error on the Z-mass of about 1.4 MeV and on the Z-width of about 1.5 MeV.

The steel-concrete cores of the LEP bending magnets were built of regularly spaced steel laminations, the spaces being filled with cement mortar. The effects of compressive stresses were studied on models and the long term behaviour has been monitored during operation of the LEP machine over a period of four years. The requirements for stability and reproducibility of the magnetic field have increased in step with the development of the accelerator and its particle detectors. After the initial ageing in the LEP tunnel, the most important parameter was the temperature coefficient. The temperatures of a number of magnet cores are therefore continuously monitored and corrections are applied to the indicated value of particle momentum as measured by NMR and a flip coil in a reference dipole connected in series with the bending magnets. This reference magnet is in turn calibrated periodically by a direct measurement of flux variations in a loop mounted in the lower poles of all bending magnets installed in the tunnel. >

The absolute beam energy of LEP (Large Electron-Positron Collider) is obtained by measuring the magnetic field in a reference dipole connected in series with the bending magnets of the machine. Periodic calibrations are carried out by measuring flux variations in a one-turn induction coil embedded in the lower pole of all bending magnets. The measurement equipment is described and the results of periodic calibrations are reported. This work illustrates the value of systematic magnetic measurements of accelerator magnets. The measurement results not only provided a precise knowledge of the beam energy, but also permitted the sorting and subsequent positioning of magnets in the machine in a cost-efficient way. >

Extensive power tests of the LHC dipole magnets required the development of new techniques to study the quench and training behaviour. Magnetic measurements of short and long model dipoles have allowed to understand and quantify the time dependent behaviour of the field quality during the current flat top needed during beam injection. The experience gained is employed for the design of the measuring tools presently under construction for the series measurements of the LHC dipole magnets. The economically important issue of how many magnets have to be measured in the superconducting state is addressed in view of the field quality required for the performance of the LHC.

The 15-m long superconducting dipoles of the Large Hadron Collider (LHC) with two-in-one design are curved by about 5 mrad to follow the beam trajectory. They are supported on three cold feet to minimise the vertical sagitta induced by their 35 tonnes weight. The cold masses contain at both ends local multipolar correctors to compensate for the detrimental effect of persistent current during injection. We discuss how we measure and control the geometrical shape of the cold mass and the alignment of the associated correctors and how we identify the magnetic axis of the field-shape harmonics with respect to the expected beam reference orbit. We present results relative to prototype dipoles obtained both at room temperature and in operational conditions at 1.9 K.

All evidence indicates that new physics, and answers to some of the most profound scientific questions of our time, lie at energies around 1 TeV. To look for this new physics, the next research instrument in Europe's particle physics armory is the Large Hadron Collider (LHC). This challenging machine will use the most advanced superconducting magnet and accelerator technologies ever employed. LHC experiments are being designed to look for theoretically predicted phenomena. One of the main challenges in this new machine resides in the design and production of the superconducting dipoles used to steer the particles around the 27 km underground tunnel. These so-called cryodipoles are composed of an external vacuum tube and an insert, appropriately named the cold mass, that contains the particle tubes, the superconducting coil and will be cooled using superfluid Helium to 1.9 K. The particle beam must be placed inside the magnetic field with a sub-millimeter accuracy, this requires in turn that the relative displacements between the vacuum tube and the cold-mass must be monitored with accuracy. Due to the extreme condition environmental conditions (the displacement measurement must be made in vacuum and between two points with a temperature difference of more than 200°C) no adequate existing monitoring system was found for this application. It was therefore decided to develop an op tical sensor suitable for this application. This contribution describes the development of this novel sensor and the first measurements performed on the LHC cryodipoles

All evidence indicates that new physics, and answers to some of the most profound scientific questions of our time, lie at energies around 1 TeV. To look for this new physics, the next research instrument in Europe's particle physics armory is the Large Hadron Collider (LHC). This challenging machine will use the most advanced superconducting magnet and accelerator technologies ever employed. LHC experiments are being designed to look for theoretically predicted phenomena. One or the main challenges in this new machine resides in the design and production of the superconducting dipoles used to steer the particles around the 27 km underground tunnel. These so-called cryodipoles are composed of an external vacuum tube and an insert, appropriately named the cold mass, that contains the particle tubes, the superconducting coil and will be cooled using superfluid Helium to 1.9 K. The particle beam must be placed inside the magnetic field with a sub-millimeter accuracy, this requires in turn that the relative displacements between the vacuum tube and the cold-mass must be monitored with accuracy. Due to the extreme condition environmental conditions (the displacement measurement must be made in vacuum and between two points with a temperature difference of more than 200°C) no adequate existing monitoring system was found for this application. It was therefore decided to develop an optical sensor suitable for this application. This contribution describes the development of this novel sensor and the first measurements performed on the LHC cryodipoles.

We describe here a new harmonic coil system for the field measurement of the superconducting, twin aperture LHC dipoles and the associated corrector magnets. Besides field measurements the system can be used as an antenna to localize the quench origin. The main component is a 16 m long rotating shaft, made up of 13 ceramic segments, each carrying two tangential coils plus a central radial coil, all working in parallel. The segments are connected with flexible Ti-alloy bellows, allowing the piecewise straight shaft to follow the curvature of the dipole while maintaining high torsional rigidity. At each interconnection the structure is supported by rollers and ball bearings, necessary for the axial movement for installation and for the rotation of the coil during measurement. Two such shafts are simultaneously driven by a twin-rotating unit, thus measuring both apertures of a dipole at the same time. This arrangement allows very short measurement times (typically 10 s) and is essential to perform cold magnetic measurements of all dipoles. The coil surface and direction are calibrated using a reference dipole. In this paper we describe the twin rotating coil system and its calibration facility, and we give the typical resolution and accuracy achieved with the first commissioned unit.

With the test of the first full scale prototype in June-July 1998, the R&D on the long superconducting dipoles based on the LHC design of 1993-95 has come to an end. This second generation of long magnets has a 56 mm coil aperture, is wound with 15 mm wide cable arranged in a 5 coil block layout. The series includes four 10 m long model dipoles, whose coils have been wound and collared in industry and the cold mass assembled and cryostated at CERN, as well as one 15 m long dipole prototype, manufactured totally in industry in the framework of a CERN-INFN collaboration for the LHC. After a brief description of particular features of the design and of the manufacturing, test results are reported and compared with the expectations. One magnet reached the record field for long model dipoles of 9.8 T but results have not been well reproducible from magnet to magnet. Guidelines for modifications that will appear in the next generation of long magnets, based on a six block coil design, are indicated in the conclusions. (10 refs).

High field superconducting dipole magnets were manufactured in industry or at CERN as model magnets for the future Large Hadron Collider (LHC) particle accelerator and tested in superfluid helium. The pick-up coil method is now in use to precisely locate the origin of training quenches and to monitor the propagation of the transition. The improvements made on this diagnostic method is reviewed. This experience allows the location of the onset of the quenches both axially and in the cross section of the winding even for magnets equipped with a minimum of voltage taps on the winding. The location of training quenches are now understood to be related to the structure of the superconducting coil. >

The magnetic measurement of more than 1300 LHC dipoles comprises the content of higher harmonic field components, field direction and field integrals. The measurements will be carried out along a warm bore installed inside the magnet cold bore, thus allowing the use of rotating coils at room temperature. This coil, together with Hall and NMR detectors is mounted at one end of a 12.5 m long shaft which is specially designed for very high rotational stiffness and which is controlled from its far end by a motor, an angular encoder and a level meter, all standard components placed outside the magnetic field without space restrictions. Particular emphasis has been put on the user-friendliness of the bench and its automated, computer-controlled operation requiring a minimum of staff, an important issue during production measurements of large series of magnets. The bench and its performance and precision achieved during its commissioning are described. >

An unexpected magnetisation of the thin nickel layer of the LEP dipole vacuum chamber has been identified as the main cause of the large horizontal to vertical optical coupling found during the LEP commissioning. Even though the betatron coupling could be much weakened by changing the difference between the tunes from 8 to 6, it was decided, after some tests, to suppress the source itself by demagnetizing the nickel layer of every chamber. An "in situ" method avoiding a removal of the chambers has been developed. The coupling has been reduced by more than a factor 5. The demagnetization suppresses a constraint on the betatron tunes and weakens the horizontal betatron spin resonances. >

Power tests and magnetic measurements have been performed on various 1-m-long LHC (Large Hadron Collider) dipole model magnets. Single- and twin-aperture magnets were energized up to peak fields above 9 T. Quench behavior, improvements in the test facility, and losses in the superconductors were examined. The field quality was measured with rotating coils immersed directly in the 1.8 K bath of the vertical cryostat. The design of these coils and the achieved measurement precision are presented. Preliminary measurements of the persistent currents show an unexpected time-dependent decay of the field harmonics. >

The 3304 steel-concrete cores of the LEP (Large Electron Positron colliding beam accelerator) bending magnets have been individually measured to determine the excitation characteristics (field integral on central orbit versus current), and one out of ten has been submitted to a complete measurement of the field pattern in the aperture. The end and junction effects, as well as the field distortion due to the vacuum chamber both in static conditions (due to residual magnetism of the chamber materials) and during field ramping (influence of eddy currents), have been determined on some average cores. The authors briefly describe the measuring benches and give the average values and RMS (root-mean-square) dispersions of the dipole, quadrupole, sextupole, octupole, and decapole components seen by the beam at different field levels and during ramping. The effects on the machine parameters are analyzed for each component and compared with results obtained in the first injection tests. >

Appareil specialement concu pour mesurer la coercivite de toles d'acier sans decouper d'echantillon, destine au controle de la production de 11000 tonnes de toles d'acier pour les dipoles LEP

The steel-concrete cores of the Large Electron Positron colliding-beam accelerator dipole magnets are built of regularly spaced soft-magnetic-steel laminations, the spaces being filled with cement mortar. The effect of compressive stresses on the permeability and the coercivity of soft magnetic steel has been measured and the consequences for magnetic characteristics of the cores have been evaluated. By controlled straining of the aged cores in a hydraulic device, the tension in the mortar is brought locally to exceed the rupture limit. Thus, the compressive stresses in the steel laminations are partially relieved and the loss of bending strength in the dipoles is reduced. The excitation characteristics of the cores are measured by means of a fixed set of excitation windings and measuring coils into which the cores are moved after stress relieving. These measurements include determination of the equivalent surface areas of flux loops, which are embedded in the lower poles and will permit measurement of the field integral on the center line during LEP operation. >

The eight superconducting quadrupoles and their cryogenic equipment for this insertion were installed in the ISR at the end of 1980. The insertion has been used to assess the problems of running a superconducting insertion in a storage ring as well as to provide high luminosity for physics. The luminosity is increased at intersection 8 by a factor of 7. By means of dedicated collimators and orbit corrections, safe working conditions could be established for the superconducting magnets during injection, accumulation, stable beam periods and when dumping the beams. Quenches were mainly caused by large accidental beam losses. Operating parameters for all standard beam energies, including acceleration to 31.4 GeV/c, have been established. At 26.6 GeV/c, with currents of 30.6 A in ring 1 and 30.3 A in ring 2, a luminosity of 1.4 1032 cm-2s-1 was obtained in the insertion. This is the highest luminosity reached so far in storage rings and it was obtained during a physics run. Satisfactory beam conditions could also be provided for antiproton physics at 26.6 GeV/c in ISR with both low-s insertions on, in I1 and I8, respectively.

A focusing insertion will be constructed at an intersection of the ISR, to achieve a reduction of the effective beam height by about a factor 6 in the interaction diamond and a corresponding increase of the luminosity. It will contain eight superconducting quadrupole magnets, capable of producing gradients of 43 Tm-1 in a warm bore of 173 mm diameter: four of them have a magnetic length of 1.15 m and four of 0.65 m. The magnets are also equipped with sextupole windings, to match the gradients to particle momenta over the beam width, and with dodecapole correction windings. After construction and successful operation of a prototype magnet in the laboratory, competitive tenders were obtained from industry on the basis of technical specifications and manufacturing drawings. The magnets proper and the cryostats are being manufactured under two separate contracts. The insertion will be installed within 1980 at intersection I8, for use in physics experiments with a large magnetic spectrometer.

This paper describes two measuring devices specially conceived in view of the fabrication by industry of the coils of the eight superconducting quadrupole magnets for the CERN ISR high-luminosity insertion. The first device is an automatic bench for the precise measurement of the SC wire dimensions. Measurements are performed under a pressure of 20 MPa and with an accuracy of ±0.003 mm. The second device allows the immediate detection of any short-circuit which may occur during winding. It is based on the continuous monitoring and recording of the d.c. resistance of the whole length of the SC wire during all winding and impregnation processes.

A total of 30.000 meters of NbTi solid multifilamentary superconductor, I_{c} \sim 2500 A at 6 T, was tested. For each stretch of wire received, measurements were made to check if the wire met the specifications. The specification and the measuring set-up are described. Systematic measurements of the critical currents, Cu : SC ratio, Ti content and wire size are discussed. A strong variation in the critical current could be correlated to a strong variation in the Ti content.

Eight superconducting quadrupoles for a high-luminosity insertion in the ISR have been produced by industrial firms according to CERN design and manufacturing specifications, and assembled and tested at CERN. The horizontal cylindrical cryostats, which contain the windings and steel yoke in a boiling helium bath, have a 173 mm warm bore. For 31 GeV beam energy, the maximum operating gradient on the quadrupole axis is 43 T m/sup -1/ and the maximum field in the windings is 5.5 T. Sextupole windings provide a linear variation of the gradient of up to 4% over the bore width and dodecapole windings trim the field pattern as a function of excitation. This paper reports about production history, acceptance tests, and performance. The results of magnetic measurements are also summarized. The insertion will be installed into the ISR as from August 1980. (7 refs).

As part of the magnet R&D program for the Large Hadron Collider (LHC), CEA Saclay has designed and built two 3-m-long, 56-mm-twin-aperture are quadrupole magnet prototypes. Extensive field quality measurements were performed during the cold-test of the second prototype. A review of the field quality data as a function of ramp rate is presented. The observed field distortions are explained in terms of inter-strand coupling currents arising from low and non-uniform resistances at the crossovers between the strands of the two-layer Rutherford-type cable. Last, the distribution of crossover resistances within the quadrupole magnet coil is determined.