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At least 613 records · Page 34

Plant‐made E2 glycoprotein single‐dose vaccine protects pigs against classical swine fever

Abstract Classical Swine Fever Virus ( CSFV ) causes classical swine fever, a highly contagious hemorrhagic fever affecting both feral and domesticated pigs. Outbreaks of CSF in Europe, Asia, Africa and South America had significant adverse impacts on animal health, food security and the pig industry. The disease is generally contained by prevention of exposure through import restrictions ( e.g . banning import of live pigs and pork products), localized vaccination programmes and culling of infected or at‐risk animals, often at very high cost. Current CSFV ‐modified live virus vaccines are protective, but do not allow differentiation of infected from vaccinated animals ( DIVA ), a critical aspect of disease surveillance programmes. Alternatively, first‐generation subunit vaccines using the viral protein E2 allow for use of DIVA diagnostic tests, but are slow to induce a protective response, provide limited prevention of vertical transmission and may fail to block viral shedding. CSFV E2 subunit vaccines from a baculovirus/insect cell system have been developed for several vaccination campaigns in Europe and Asia. However, this expression system is considered expensive for a veterinary vaccine and is not ideal for wide‐spread deployment. To address the issues of scalability, cost of production and immunogenicity, we have employed an Agrobacterium ‐mediated transient expression platform in Nicotiana benthamiana and formulated the purified antigen in novel oil‐in‐water emulsion adjuvants. We report the manufacturing of adjuvanted, plant‐made CSFV E2 subunit vaccine. The vaccine provided complete protection in challenged pigs, even after single‐dose vaccination, which was accompanied by strong virus neutralization antibody responses.

60 APPLIED LIFE SCIENCES↗

Design, testing and emplacement of sand-bentonite for the construction of a gas-permeable seal test (gast)

The main aim of a gas-permeable seal is to increase the gas transport capacity of the backfilled underground structures without compromising the radionuclide retention capacity of the engineered barrier system or the host rock. Such a seal, proposed by NAGRA as part of the 'Engineered Gas Transport System' in a L/ILW repository, considers specially designed backfill and sealing materials such as sand/bentonite (S/B) mixtures with a bentonite content of 20- 30%. NAGRA's RD and D plan foresees demonstrating the construction and performance of repository seals and improving the understanding and the database for reliably predicting water and gas transport through these systems. The fluid flow and gas transport properties of these backfills have been determined at the laboratory scale and through modelling the maximum gas pressures in the near field of a repository system and the gas flow rates have been evaluated. Within this context, the Gas-permeable Seal Test (GAST) was constructed at Grimsel Test Site (GTS) to validate the effective functioning of gas-permeable seals at realistic scale. The intrinsic permeability of such seals should be in the order of 10-18 m2. Because the construction of S/B seals is not common practice for construction companies, a stepwise approach was followed to evaluate different construction and quality assurance methods. As a first step, an investigation campaign with simple tests in the laboratory and in the field followed by 1:1 scale pre-tests at GTS was performed. Through this gradual increase of the degree of complexity, practical experience was gained and confidence in the methods and procedures to be used was built, which allowed reliably producing and working with S/B mixtures at a realistic scale. During the whole pre-testing phase, a quality assurance (QA) programme for S/B mixtures was developed and different methods were assessed. They helped to evaluate and choose appropriate emplacement techniques and methodologies to achieve the target S/B dry density of 1.70 g/cm{sup 3}, which results in the desired intrinsic permeability throughout the experiment. The final QA methodology was targeted at engineering measures to decide if the work can proceed, and at producing high resolution material properties database for future water and gas transport modelling activities. The different applied QA techniques included standard core cutter tests, the application of neutron-gamma (Troxler) probes and two mass balance methods (2D and 3D). The methods, looking at different representative scales, have provided only slightly different results and showed that the average density of the emplaced S/B plug was between 1.65 and 1.73 g/cm{sup 3}. Spatial variability of dry densities was observed at decimeter scale. Overall, the pre-testing and QA programme performed for the GAST project demonstrated how the given design criteria and requirements can be met by appropriately planning and designing the material emplacement. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Activities ONDRAF/NIRAS related to the decommissioning of nuclear facilities

Since 1980, the Agency is responsible by law for the safe management of all radioactive waste produced in Belgium, including decommissioning wastes. By the law of 11 January 1991 and the implementing Royal Decree of 16/10/1991, ONDRAF/NIRAS has been entrusted with a mission concerning the decommissioning of nuclear facilities. This mission involves the collection and assessment of data concerning decommissioning forecasts for nuclear facilities, the approval of facilities' decommissioning programmes, the establishment - in consultation with operators - of financing conditions for decommissioning, as well as the implementation of these programmes on request by the operator, or in the case of its failure to do so. This is the case for the company Best Medical Belgium SA located at Fleurus (MDS Nordion SA, till April 2011), which produced radioisotopes for medical applications and went bankrupt in 2012. These installations have been entrusted to ONDRAF/NIRAS. A plan of action was developed for taking over the operations in the framework of remediation and decommissioning. Steps have been taken to integrate his new role as a nuclear operator. The installations of Best Medical Belgium SA are now referred to as the 'O/N - Site Fleurus.' Nuclear facility operators, or any person requesting to operate a nuclear facility, are obliged to provide ONDRAF/NIRAS, under their responsibility and in due time, with all the necessary information concerning these facilities' decommissioning forecasts, the nature, quantities and dates of transfer of the resulting waste, and the financing conditions for these facilities' decommissioning. In order to make the necessary funds available for decommissioning a nuclear facility when it will be shut down, operators are obliged to establish provisions during the facility's active life. These provisions are calculated in such a way that the total amount established at the time of the final shutdown covers all costs resulting from the facility's final phase, namely the preparation of decommissioning, decontamination, more or less long-term maintenance, dismantling, treatment, conditioning and disposal of waste produced during this phase. In order to face to multiple and repeated evaluation processes, the Agency, already in the early 90's, started with the implementation of its own integrated data processing system, recording the physical and radiological inventories of nuclear facilities, and allowing the evaluation of the quantities of decommissioning materials and wastes as well as of the decommissioning costs of these facilities. The cost evaluations cover all decommissioning activities from final shutdown of the facility until final release from nuclear control, as well as conventional demolition and site restoration if required. Beside the information related to the inventories, the database involves so called auxiliary tables integrating unit prices of the various decontamination and dismantling techniques, unit rates for radioactive waste processing, interim storage and final disposal. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Scintillator high-gain avalanche rushing photoconductor active-matrix flat panel imager: Zero-spatial frequency x-ray imaging properties of the solid-state SHARP sensor structure

Purpose: The authors are investigating the feasibility of a new type of solid-state x-ray imaging sensor with programmable avalanche gain: scintillator high-gain avalanche rushing photoconductor active matrix flat panel imager (SHARP-AMFPI). The purpose of the present work is to investigate the inherent x-ray detection properties of SHARP and demonstrate its wide dynamic range through programmable gain. Methods: A distributed resistive layer (DRL) was developed to maintain stable avalanche gain operation in a solid-state HARP. The signal and noise properties of the HARP-DRL for optical photon detection were investigated as a function of avalanche gain both theoretically and experimentally, and the results were compared with HARP tube (with electron beam readout) used in previous investigations of zero spatial frequency performance of SHARP. For this new investigation, a solid-state SHARP x-ray image sensor was formed by direct optical coupling of the HARP-DRL with a structured cesium iodide (CsI) scintillator. The x-ray sensitivity of this sensor was measured as a function of avalanche gain and the results were compared with the sensitivity of HARP-DRL measured optically. The dynamic range of HARP-DRL with variable avalanche gain was investigated for the entire exposure range encountered in radiography/fluoroscopy (R/F) applications. Results: The signal from HARP-DRL as a function of electric field showed stable avalanche gain, and the noise associated with the avalanche process agrees well with theory and previous measurements from a HARP tube. This result indicates that when coupled with CsI for x-ray detection, the additional noise associated with avalanche gain in HARP-DRL is negligible. The x-ray sensitivity measurements using the SHARP sensor produced identical avalanche gain dependence on electric field as the optical measurements with HARP-DRL. Adjusting the avalanche multiplication gain in HARP-DRL enabled a very wide dynamic range which encompassed all clinically relevant medical x-ray exposures. Conclusions: This work demonstrates that the HARP-DRL sensor enables the practical implementation of a SHARP solid-state x-ray sensor capable of quantum noise limited operation throughout the entire range of clinically relevant x-ray exposures. This is an important step toward the realization of a SHARP-AMFPI x-ray flat-panel imager.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

SU-E-T-429: Feasibility Study On Three-Dimensional GRID Therapy in Conventional Linacs

Purpose: Two-dimensional GRID therapy, traditionally planned and delivered using a dedicated GRID block or MLC modulation, has shown clinical efficacy in treating bulky tumors. However, the large dose to normal tissues outside target can be limiting. We hypothesize that modulation in the third dimension will improve dose sparing of normal tissues, maximize the bystander effect within the target, and ultimately improve the therapy effectiveness. This study aims to investigate the feasibility of a three-dimensional GRID technique using conventional LINACs to achieve a 3D lattice of high dose volumes within a target. Methods: Datasets of patient’s having large tumor sizes were used to investigate the planning and delivering of 3D GRID using a Varian TrueBeam linac. Original patient contours of PTV are exported from a TPS to DICOManTX where 3D GRID targets are generated in programmable configurations. A structure of avoidance (SOA), i.e., PTV minus GRID targets, is also generated to facilitate inverse planning to achieve the desired pattern. The artificial structures were sent back to the TPS where an IMRT or VMAT plan is designed to deliver a desired high dose to GRID targets while minimizing the dose to the SOA as much as possible. Results: The programmable GRID target generator enables us to modify the target geometry to maximize the peak-to-valley ratio. Preliminary results show that plans based on spherical GRID targets achieve a higher peak-to-valley dose ratio compared with cylindrical targets. High dose spillage outside the target was eliminated. IMRT planning requires the number of beams to be larger than 16, while for VMAT the number of arcs should be at least 4 in order to achieve dosimetric goals. Conclusion: Planning and delivering 3D GRID therapy using conventional LINACs was shown to be feasible. More research and development are required before this new modality can be implemented clinically.

60 APPLIED LIFE SCIENCES↗

SU-F-T-672: A Novel Kernel-Based Dose Engine for KeV Photon Beams

Purpose: Mimicking state-of-the-art patient radiotherapy with high precision irradiators for small animals allows advanced dose-effect studies and radiobiological investigations. One example is the implementation of pre-clinical IMRT-like irradiations, which requires the development of inverse planning for keV photon beams. As a first step, we present a novel kernel-based dose calculation engine for keV x-rays with explicit consideration of energy and material dependencies. Methods: We follow a superposition-convolution approach adapted to keV x-rays, based on previously published work on micro-beam therapy. In small animal radiotherapy, we assume local energy deposition at the photon interaction point, since the electron ranges in tissue are of the same order of magnitude as the voxel size. This allows us to use photon-only kernel sets generated by MC simulations, which are pre-calculated for six energy windows and ten base materials. We validate our stand-alone dose engine against Geant4 MC simulations for various beam configurations in water, slab phantoms with bone and lung inserts, and on a mouse CT with (0.275mm)3 voxels. Results: We observe good agreement for all cases. For field sizes of 1mm{sup 2} to 1cm{sup 2} in water, the depth dose curves agree within 1% (mean), with the largest deviations in the first voxel (4%) and at depths>5cm (<2.5%). The out-of-field doses at 1cm depth agree within 8% (mean) for all but the smallest field size. In slab geometries, the mean agreement was within 3%, with maximum deviations of 8% at water-bone interfaces. The γ-index (1mm/1%) passing rate for a single-field mouse irradiation is 71%. Conclusion: The presented dose engine yields an accurate representation of keV-photon doses suitable for inverse treatment planning for IMRT. It has the potential to become a significantly faster yet sufficiently accurate alternative to full MC simulations. Further investigations will focus on energy sampling as well as calculation times. Research at ICR is also supported by Cancer Research UK under Programme C33589/A19727 and NHS funding to the NIHR Biomedical Research Centre at RMH and ICR. MFF is supported by Cancer Research UK under Programme C33589/A19908.

43 PARTICLE ACCELERATORS↗

SU-G-BRA-16: Target Dose Comparison for Dynamic MLC Tracking and Mid- Ventilation Planning in Lung Radiotherapy Subject to Intrafractional Baseline Drifts

Purpose: Lung tumor motion during radiotherapy can be accounted for by expanded treatment margins, for example using a mid-ventilation planning approach, or by localizing the tumor in real-time and adapting the treatment beam with multileaf collimator (MLC) tracking. This study evaluates the effect of intrafractional changes in the average tumor position (baseline drifts) on these two treatment techniques. Methods: Lung stereotactic treatment plans (9-beam IMRT, 54Gy/3 fractions, mean treatment time: 9.63min) were generated for three patients: either for delivery with MLC tracking (isotropic GTV-to-PTV margin: 2.6mm) or planned with a mid-ventilation approach and delivered without online motion compensation (GTV-to-PTV margin: 4.4-6.3mm). Delivery to a breathing patient was simulated using DynaTrack, our in-house tracking and delivery software. Baseline drifts in cranial and posterior direction were simulated at a rate of 0.5, 1.0 or 1.5mm/min. For dose reconstruction, the corresponding 4DCT phase was selected for each time point of the delivery. Baseline drifts were accounted for by rigidly shifting the CT to ensure correct relative beam-to-target positioning. Afterwards, the doses delivered to each 4DCT phase were accumulated deformably on the mid-ventilation phase using research RayStation v4.6 and dose coverage of the GTV was evaluated. Results: When using the mid-ventilation planning approach, dose coverage of the tumor deteriorated substantially in the presence of baseline drifts. The reduction in D98% coverage of the GTV in a single fraction ranged from 0.4-1.2, 0.6-3.3 and 4.5-6.2Gy, respectively, for the different drift rates. With MLC tracking the GTV D98% coverage remained unchanged (+/− 0.1Gy) regardless of drift. Conclusion: Intrafractional baseline drifts reduce the tumor dose in treatments based on mid-ventilation planning. In rare, large target baseline drifts tumor dose coverage may drop below the prescription, potentially affecting clinical outcome in hypofractionated treatment protocols. Dynamic MLC tracking preserves tumor dose coverage even in the presence of extreme baseline drifts. We acknowledge financial and technical support of the MLC tracking research from Elekta AB. Research at ICR is supported by CRUK under Programme C33589/A19727 and NHS funding to the NIHR Biomedical Research Centre at RMH and ICR. MFF is supported by CRUK under Programme C33589/A19908.

60 APPLIED LIFE SCIENCES↗

WE-AB-209-08: Novel Beam-Specific Adaptive Margins for Reducing Organ-At-Risk Doses

Purpose: Current practice of using 3D margins in radiotherapy with high-energy photon beams provides larger-than-required target coverage. According to the photon depth-dose curve, target displacements in beam direction result in minute changes in dose delivered. We exploit this behavior by generating margins on a per-beam basis which simultaneously account for the relative distance of the target and adjacent organs-at-risk (OARs). Methods: For each beam, we consider only geometrical uncertainties of the target location perpendicular to beam direction. By weighting voxels based on its proximity to an OAR, we generate adaptive margins that yield similar overall target coverage probability and reduced OAR dose-burden, at the expense of increased target volume. Three IMRT plans, using 3D margins and 2D per-beam margins with and without adaptation, were generated for five prostate patients with a prescription dose Dpres of 78Gy in 2Gy fractions using identical optimisation constraints. Systematic uncertainties of 1.1, 1.1, 1.5mm in the LR, SI, and AP directions, respectively, and 0.9, 1.1, 1.0mm for the random uncertainties, were assumed. A verification tool was employed to simulate the effects of systematic and random errors using a population size of 50,000. The fraction of the population that satisfies or violates a given DVH constraint was used for comparison. Results: We observe similar target coverage across all plans, with at least 97.5% of the population meeting the D98%>95%Dpres constraint. When looking at the probability of the population receiving D5<70Gy for the rectum, we observed median absolute increases of 23.61% (range, 2.15%–27.85%) and 6.97% (range, 0.65%–17.76%) using per-beam margins with and without adaptation, respectively, relative to using 3D margins. Conclusion: We observed sufficient and similar target coverage using per-beam margins. By adapting each per-beam margin away from an OAR, we can further reduce OAR dose without significantly lowering target coverage probability by irradiating more less-important tissues. This work is supported by Cancer Research UK under Programme C33589/A19908. Research at ICR is also supported by Cancer Research UK under Programme C33589/A19727 and NHS funding to the NIHR Biomedical Research Centre at RMH and ICR.

07 ISOTOPE AND RADIATION SOURCES↗

TH-AB-202-03: A Novel Tool for Computing Deliverable Doses in Dynamic MLC Tracking Treatments

Purpose: In tracked dynamic multi-leaf collimator (MLC) treatments, segments are continuously adapted to the target centroid motion in beams-eye-view. On-the-fly segment adaptation, however, potentially induces dosimetric errors due to the finite MLC leaf width and non-rigid target motion. In this study, we outline a novel tool for computing the 4d dose of lung SBRT plans delivered with MLC tracking. Methods: The following automated workflow was developed: A) centroid tracking, where the initial segments are morphed to each 4dCT phase based on the beams-eye-view GTV shift (followed by a dose calculation on each phase); B) re-optimized tracking, in which all morphed initial plans from (A) are further optimised (“warm-started”) in each 4dCT phase using the initial optimisation parameters but phase-specific volume definitions. Finally, both dose sets are accumulated to the reference phase using deformable image registration. Initial plans were generated according to the RTOG-1021 guideline (54Gy, 3-Fx, equidistant 9-beam IMRT) on the peak-exhale (reference) phase of a phase-binned 4dCT. Treatment planning and delivery simulations were performed in RayStation (research v4.6) using our in-house segment-morphing algorithm, which directly links to RayStation through a native C++ interface. Results: Computing the tracking plans and 4d dose distributions via the in-house interface takes 5 and 8 minutes respectively for centroid and re-optimized tracking. For a sample lung SBRT patient with 14mm peak-to-peak motion in sup-inf direction, mainly perpendicular leaf motion (0-collimator) resulted in small dose changes for PTV-D95 (−13cGy) and GTV-D98 (+18cGy) for the centroid tracking case compared to the initial plan. Modest reductions of OAR doses (e.g. spinal cord D2: −11cGy) were achieved in the idealized tracking case. Conclusion: This study presents an automated “1-click” workflow for computing deliverable MLC tracking doses in RayStation. Adding a non-deliverable re-optimized tracking scenario is expected to help quantify plan robustness for more challenging patients with anatomy deformations. We acknowledge support of the MLC tracking research from Elekta AB. MFF is supported by Cancer Research UK under Programme C33589/A19908. Research at ICR is also supported by Cancer Research UK under Programme C33589/A19727 and NHS funding to the NIHR Biomedical Research Centre at RMH and ICR.

60 APPLIED LIFE SCIENCES↗

TH-CD-202-12: Online Inter-Beam Replanning Based On Real-Time Dose Reconstruction

Purpose: This work provides a proof-of-concept study for online replanning during treatment delivery for step-and-shoot prostate SBRT, based on real-time dose reconstruction. Online replanning is expected to improve the trade-off between target coverage and organ-at-risk dose in the presence of intra-fractional motion. Methods: We have implemented an online replanning workflow on top of our previously reported real-time dose reconstruction software which connects to an Elekta research linac. The treatment planning system DynaPlan was extended to (1) re-optimize and sequence treatment plans (in clockwise beam order) before each beam, based on actual delivered dose, in a timeframe limited by the gantry rotation between subsequent beams, and (2) send the respective segments to the delivery control software DynaTrack which starts/continues treatment immediately.To investigate the impact of a reduced safety margin, we have created and delivered (on a linac emulator) a conventional CTV+5/3mm (I) and a reduced CTV+1mm margin (II) treatment plan for a prostate patient. We have assessed CTV coverage with and without inter-beam replanning, all exposed to a gradual target shift of 0–5mm in posterior and inferior direction from start until the end of delivery. Results: For the reconstructed conventional plan (I), D98 for CTV was 100% of D98 of the planned dose. For the reconstructed margin-reduced plan (II), D98 for CTV was 95% of the planned D98 without replanning, but could be recovered to 99% by replanning for each beam. Plan (II) with replanning resulted in a decrease for bladder V90% by 88% and an increase to rectum V90% by 9% compared to the conventional plan (I). Dose calculation/accumulation was performed in <15ms per MLC aperture, replanning in <15s per beam. Conclusion: We have shown that online inter-beam replanning is technically feasible and potentially allows for a margin reduction. Future investigation considering motion-robust replanning optimization parameters is in progress. We acknowledge support of the MLC research from Elekta AB. This work is supported by Cancer Research UK under Programme C33589/A19908. Research at ICR is also supported by Cancer Research UK under Programme C33589/A19727 and NHS funding to the NIHR Biomedical Research Centre at RMH and ICR.

60 APPLIED LIFE SCIENCES↗

Controlling quantum many-body dynamics in driven Rydberg atom arrays

Dynamic stabilization of an array Large-scale systems comprising one-dimensional chains and two-dimensional arrays of excited atoms held in a programmable optical lattice are a powerful platform with which to simulate emergent phenomena. Bluvstein et al. built an array of up to 200 Rydberg atoms and subjected the system to periodic excitation. Under such driven excitation, they found that the array of atoms stabilized, freezing periodically into what looked like time crystals. Understanding and controlling the dynamic interactions in quantum many-body systems lies at the heart of contemporary condensed matter physics and the exotic phenomena that can occur. Science , this issue p. 1355

Science & Technology - Other Topics↗

Structure-guided discovery of ancestral CRISPR-Cas13 ribonucleases

The RNA-guided ribonuclease CRISPR-Cas13 enables adaptive immunity in bacteria and programmable RNA manipulation in heterologous systems. Cas13s share limited sequence similarity, hindering discovery of related or ancestral systems. Here, to address this, we developed an automated structural-search pipeline to identify an ancestral clade of Cas13 (Cas13an) and further trace Cas13 origins to defense-associated ribonucleases. Despite being one-third the size of other Cas13s, Cas13an mediates robust programmable RNA depletion and defense against diverse bacteriophages. However, unlike its larger counterparts, Cas13an uses a single active site for both CRISPR RNA processing and RNA-guided cleavage, revealing that the ancestral nuclease domain has two modes of activity. Discovery of Cas13an deepens our understanding of CRISPR-Cas evolution and expands opportunities for precision RNA editing, showcasing the promise of structure-guided genome mining.

59 BASIC BIOLOGICAL SCIENCES↗

Hadron structure and spectroscopy at COMPASS. Overview of certain tasks

COMPASS is a fixed-target experiment at CERN with a long history and intense and diverse physics programme. In the Review we consider particular points of the existing and possible future programme: test of the chiral theory predictions with hadron beam, search for exotic charmonia, study of the EMC effect in the Drell–Yan process, search for production of bound p p-bar states and study of prompt photon production in hadronic interactions.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

An experiment for electron-hadron scattering at the LHC

Abstract Novel considerations are presented on the physics, apparatus and accelerator designs for a future, luminous, energy frontier electron-hadron ( eh ) scattering experiment at the LHC in the thirties for which key physics topics and their relation to the hadron-hadron HL-LHC physics programme are discussed. Demands are derived set by these physics topics on the design of the LHeC detector, a corresponding update of which is described. Optimisations on the accelerator design, especially the interaction region (IR), are presented. Initial accelerator considerations indicate that a common IR is possible to be built which alternately could serve eh and hh collisions while other experiments would stay on hh in either condition. A forward-backward symmetrised option of the LHeC detector is sketched which would permit extending the LHeC physics programme to also include aspects of hadron-hadron physics. The vision of a joint eh and hh physics experiment is shown to open new prospects for solving fundamental problems of high energy heavy-ion physics including the partonic structure of nuclei and the emergence of hydrodynamics in quantum field theory while the genuine TeV scale DIS physics is of unprecedented rank.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

The ALICE experiment: a journey through QCD

The ALICE experiment was proposed in 1993, to study strongly-interacting matter at extreme energy densities and temperatures. This proposal entailed a comprehensive investigation of nuclear collisions at the LHC. Its physics programme initially focused on the determination of the properties of the quark–gluon plasma (QGP), a deconfined state of quarks and gluons, created in such collisions. The ALICE physics programme has been extended to cover a broader ensemble of observables related to Quantum Chromodynamics (QCD), the theory of strong interactions. The experiment has studied Pb–Pb, Xe–Xe, p–Pb and pp collisions in the multi-TeV centre of mass energy range, during the Run 1–2 data-taking periods at the LHC (2009–2018). The aim of this review is to summarise the key ALICE physics results in this endeavor, and to discuss their implications on the current understanding of the macroscopic and microscopic properties of strongly-interacting matter at the highest temperatures reached in the laboratory. It will review the latest findings on the properties of the QGP created by heavy-ion collisions at LHC energies, and describe the surprising QGP-like effects in pp and p–Pb collisions. Measurements of few-body QCD interactions, and their impact in unraveling the structure of hadrons and hadronic interactions, will be discussed. ALICE results relevant for physics topics outside the realm of QCD will also be touched upon. Finally, prospects for future measurements with the ALICE detector in the context of its planned upgrades will also be briefly described.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Input to the European strategy for particle physics: strong-field quantum electrodynamics

This document sets out the intention of the strong-field QED community to carry out, both experimentally and numerically, high-statistics parametric studies of quantum electrodynamics in the non-perturbative regime, at fields approaching and exceeding the critical or ‘Schwinger’ field of QED (F qed ≈ m 2 c 3 / eh ≈ 1.3 x 10 18 V/m) in the rest frame of a charged particle. In this regime, several exotic and fascinating phenomena are predicted to occur that have never been directly observed in the laboratory. These include Breit–Wheeler pair production, vacuum birefringence, and quantum radiation reaction. This experimental programme will also serve as a stepping stone towards studies of elusive phenomena such as elastic scattering of real photons and the conjectured perturbative breakdown of QED at extreme fields. State-of-the-art high-power laser facilities in Europe and beyond are starting to offer unique opportunities to study this uncharted regime at the intensity frontier, which is highly relevant also for the design of future multi-TeV lepton colliders. A transition from qualitative observational experiments to quantitative and high-statistics measurements can only be performed with large-scale collaborations and with systematic experimental programmes devoted to the optimisation of several aspects of these complex experiments, including detector developments, stability and tolerances studies, and laser technology.

Sarri, G. [Queen’s University Belfast (United King↗

FCC-hh: The Hadron Collider

Particle physics has arrived at an important moment of its history. The discovery of the Higgs boson, with a mass of 125 GeV, completes the matrix of particles and interactions that has constituted the “Standard Model” for several decades. This model is a consistent and predictive theory, which has so far proven successful at describing all phenomena accessible to collider experiments. However, several experimental facts do require the extension of the Standard Model and explanations are needed for observations such as the abundance of matter over antimatter, the striking evidence for dark matter and the non-zero neutrino masses. Theoretical issues such as the hierarchy problem, and, more in general, the dynamical origin of the Higgs mechanism, do likewise point to the existence of physics beyond the Standard Model. This report contains the description of a novel research infrastructure based on a highest-energy hadron collider with a centre-of-mass collision energy of 100 TeV and an integrated luminosity of at least a factor of 5 larger than the HL-LHC. It will extend the current energy frontier by almost an order of magnitude. The mass reach for direct discovery will reach several tens of TeV, and allow, for example, to produce new particles whose existence could be indirectly exposed by precision measurements during the earlier preceding e+e– collider phase. This collider will also precisely measure the Higgs self-coupling and thoroughly explore the dynamics of electroweak symmetry breaking at the TeV scale, to elucidate the nature of the electroweak phase transition. WIMPs as thermal dark matter candidates will be discovered, or ruled out. As a single project, this particle collider infrastructure will serve the world-wide physics community for about 25 years and, in combination with a lepton collider (see FCC conceptual design report volume 2), will provide a research tool until the end of the 21st century. Collision energies beyond 100 TeV can be considered when using high-temperature superconductors. The European Strategy for Particle Physics (ESPP) update 2013 stated “To stay at the forefront of particle physics, Europe needs to be in a position to propose an ambitious post-LHC accelerator project at CERN by the time of the next Strategy update”. The FCC study has implemented the ESPP recommendation by developing a long-term vision for an “accelerator project in a global context”. This document describes the detailed design and preparation of a construction project for a post-LHC circular energy frontier collider “in collaboration with national institutes, laboratories and universities worldwide”, and enhanced by a strong participation of industrial partners. Now, a coordinated preparation effort can be based on a core of an ever-growing consortium of already more than 135 institutes worldwide. The technology for constructing a high-energy circular hadron collider can be brought to the technology readiness level required for constructing within the coming ten years through a focused R&D programme. The FCC-hh concept comprises in the baseline scenario a power-saving, low-temperature superconducting magnet system based on an evolution of the Nb3Sn technology pioneered at the HL-LHC, an energy-efficient cryogenic refrigeration infrastructure based on a neon-helium (Nelium) light gas mixture, a high-reliability and low loss cryogen distribution infrastructure based on Invar, high-power distributed beam transfer using superconducting elements and local magnet energy recovery and re-use technologies that are already gradually introduced at other CERN accelerators. On a longer timescale, high-temperature superconductors can be developed together with industrial partners to achieve an even more energy efficient particle collider or to reach even higher collision energies.The re-use of the LHC and its injector chain, which also serve for a concurrently running physics programme, is an essential lever to come to an overall sustainable research infrastructure at the energy frontier. Strategic R&D for FCC-hh aims at minimising construction cost and energy consumption, while maximising the socio-economic impact. It will mitigate technology-related risks and ensure that industry can benefit from an acceptable utility. Concerning the implementation, a preparatory phase of about eight years is both necessary and adequate to establish the project governance and organisation structures, to build the international machine and experiment consortia, to develop a territorial implantation plan in agreement with the host-states’ requirements, to optimise the disposal of land and underground volumes, and to prepare the civil engineering project. Such a large-scale, international fundamental research infrastructure, tightly involving industrial partners and providing training at all education levels, will be a strong motor of economic and societal development in all participating nations. The FCC study has implemented a set of actions towards a coherent vision for the world-wide high-energy and particle physics community, providing a collaborative framework for topically complementary and geographically well-balanced contributions. This conceptual design report lays the foundation for a subsequent infrastructure preparatory and technical design phase.

43 PARTICLE ACCELERATORS↗

HE-LHC: The High-Energy Large Hadron Collider

Particle physics has arrived at an important moment of its history. The discovery of the Higgs boson, with a mass of 125 GeV, completes the matrix of particles and interactions that has constituted the “Standard Model” for several decades. This model is a consistent and predictive theory, which has so far proven successful at describing all phenomena accessible to collider experiments. However, several experimental facts do require the extension of the Standard Model and explanations are needed for observations such as the abundance of matter over antimatter, the striking evidence for dark matter and the non-zero neutrino masses. Theoretical issues such as the hierarchy problem, and, more in general, the dynamical origin of the Higgs mechanism, do likewise point to the existence of physics beyond the Standard Model. This report contains the description of a novel research infrastructure based on a high-energy hadron collider, which extends the current energy frontier by almost a factor 2 (27 TeV collision energy) and an integrated luminosity of at least a factor of 3 larger than the HL-LHC. In connection with four experimental detectors, this infrastructure will deepen our understanding of the origin of the electroweak symmetry breaking, allow a first measurement of the Higgs self-coupling, double the HL-LHC discovery reach and allow for in-depth studies of new physics signals arising from future LHC measurements. This collider would directly produce particles at significant rates at scales up to 12 TeV. The project re-uses the existing LHC underground infrastructure and large parts of the injector chain at CERN. This particle collider would succeed the HL-LHC directly and serve the world-wide physics community for about 20 years beyond the middle of the 21st century. The European Strategy for Particle Physics (ESPP) update 2013 stated “To stay at the forefront of particle physics, Europe needs to be in a position to propose an ambitious post-LHC accelerator project at CERN by the time of the next Strategy update”. The FCC study has implemented the ESPP recommendation by developing a vision for an “accelerator project in a global context”. This document describes the detailed design and preparation of a construction project for a post-LHC circular high-energy hadron collider “in collaboration with national institutes, laboratories and universities worldwide”, and enhanced by a strong participation of industrial partners. Now, a coordinated preparation effort can be based on a core of an ever-growing consortium of already more than 135 institutes worldwide. The technology for constructing a High-Energy LHC can be brought to the technology readiness level required for construction within the coming ten years through a committed and focused R&D programme. The concept comprises a power-saving, low-temperature superconducting magnet system based on an evolution of the Nb3Sn technology pioneered at the HL-LHC, an energy-efficient cryogenic refrigeration infrastructure based on a neon-helium (Nelium) light gas mixture, a high-reliability and low loss cryogen distribution infrastructure based on Invar, high-power distributed beam transfer using superconducting elements and local magnet energy recovery and re-use technologies that are already gradually introduced at other CERN accelerators. Re-use of the LHC underground civil infrastructure worth about 500 million CHF at the time of its construction, extension of the surface sites and use of the existing injector chain that also serve for a concurrently running physics programme are levers to come to a sustainable research infrastructure at the energy frontier. Strategic R&D for HE-LHC aims at minimising construction cost and energy consumption, while maximising the socio-economic impact. It needs to mitigate technology-related risks and ensure that industry can benefit from an acceptable economic utility. Concerning the implementation, a preparatory phase of about eight years is both necessary and adequate to establish the project governance and organisation structures, to build the international machine and experiment consortia, to develop a territorial implantation plan considering the constraints emerging from using the existing infrastructure and the host states’ requirements, optimising the use of land, resources and preparing the construction project. Such a large-scale, international fundamental research infrastructure, tightly involving industrial partners and providing training at all education levels, will be a strong motor of economic and societal development in all participating nations. The FCC study has implemented a set of actions towards a coherent vision for the world-wide high-energy and particle physics community, providing a collaborative framework for topically complementary and geographically well-balanced contributions. This conceptual design report lays the foundation for a subsequent infrastructure preparatory and technical design phase.

43 PARTICLE ACCELERATORS↗