Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Thermal Modelling, Conception and Design of a Cooling System for the LHC Injection Kicker Magnets Towards High Luminosity LHC Operation

The CERN Large Hadron Collider is equipped with two fast single-turn injection kicker systems that deflect the incoming particle beam onto the accelerator’s orbit. The high intensity LHC beam, circulating for many hours, can cause considerable heating of the injection kicker magnets. Finite element models have been developed and validated to study the beam induced heating and thermal behaviour of these magnets. These models are used to predict the power deposition and temperatures for various operation scenarios. According to predictions, heating issues are expected for High Luminosity LHC operation with high intensity beams unless appropriate measures are taken. Cooling of the magnet yokes is complicated as the magnets are in vacuum and are pulsed at high voltage. A description of the evolution of the studies is presented, culminating with the conception and design of a cooling system, which is thoroughly described, from the conception process to the final proposed solution

Thermal modelling, conception and design of a cooling system for the LHC injection Kicker Magnets towards High Luminosity LHC operation

The CERN Large Hadron Collider is equipped with two fast single-turn injection kicker systems that deflect the incoming particle beam onto the accelerator’s orbit. The high intensity LHC beam, circulating for many hours, can cause considerable heating of the injection kicker magnets. Finite element models have been developed and validated to study the beam induced heating and thermal behaviour of these magnets. These models are used to predict the power deposition and temperatures for various operation scenarios. According to predictions, heating issues are expected for High Luminosity LHC operation with high intensity beams unless appropriate measures are taken. Cooling of the magnet yokes is complicated as the magnets are in vacuum and are pulsed at high voltage. A description of the evolution of the studies is presented, culminating with the conception and design of a cooling system, which is thoroughly described, from the conception process to the final proposed solution

Current and Future Beam Thermal Behaviour of the LHC Injection Kicker Magnet

During Run 1 of the LHC the injection kicker magnets caused occasional operational delays due to beam induced heating with high bunch intensity and short bunch lengths. Significant upgrades were carried out to the injection kicker magnets during long shutdown 1, including a new design of beam screen to reduce the beam induced heating. Nevertheless these kicker magnets may limit the performance of HL-LHC unless additional, mitigating, measures are taken. Hence extensive simulations have been carried out to predict the distribution of the beam induced power deposition within the magnet and detailed thermal analyses carried out to predict the temperature profiles. To benchmark the simulations the predicted temperatures are compared with observables in the LHC. This paper reports on observations of the thermal behaviour of the magnet during run 2 of the LHC, with 25ns beam. In addition the measurement data is used to extrapolate temperature rise for the beam parameters expected for high-luminosity LHC

Longitudinal Impedance Analysis of an Upgraded LHC Injection Kicker Magnet

Prior to Long Shutdown 1 (LS1) one of the LHC injection kickers (MKIs) occasionally exhibited high temperatures leading to significant turnaround times. After a successful impedance mitigation campaign during LS1, the MKI ferrite yokes have remained below their Curie point and have not limited LHC's availability. However, for HL-LHC operation the MKI yokes are expected to exceed their Curie temperatures after long physics runs. To ensure uninterrupted future HL-LHC operation, a modified beam screen design, relocating some of the heat load to more easily cooled parts, and a suitable cooling system are under development as the current baseline for the HL-LHC upgrade of the MKIs. An upgraded beam screen providing such relocation has been designed, simulated and compared to the existing model. To validate simulations, two longitudinal beam coupling impedance measurement techniques have been used and the results are compared to predictions. The modified beam screen was implemented in an upgraded MKI installed in the LHC during the Year End Technical Stop (YETS) 2017/18

Thermal Mapping of SRF Cavities by Second Sound Detection With Transition Edge Sensors and Oscillating Superleak Transducers

The SRF cavity testing facilities at CERN include four vertical cryostat stations in SM18 and a cryostat for small cavities in the Cryolab. A large range of structures are tested, from Nb thin film cavities for HIE-Isolde and LHC, to bulk Nb crab cavities for HiLumi or 704 MHz 5-cell high-gradient cavities. To cope with different shapes and small series tests, thermal mapping diagnostics is deployed by sensing second sound in superfluid helium. A new type of Transition Edge Sensors (TES) has been developed in the last 2 years. These are miniature resistors of thin-film superconducting alloys, micro-produced on insulating wafers. An extensive campaign of optimization of design, fabrication process and composition was accompanied by qualification in a calibration cryostat. Reproducibility, stability, then intensity, distance and angular dependence of the response were assessed and compared to Oscillating Superleak Transducers (OST). The TES were then installed in a vertical cryostat for tests of a prototype crab cavity for HiLumi. TES are now applied to quench localization on high gradient cavities, for which the most recent results will be presented, together with the OST results

Operational experience of a prototype LHC injection kicker magnet with a low SEY coating and redistributed power deposition

In the event that it is necessary to exchange an LHC injection kicker magnet (MKI), the newly installed kicker magnet would limit operation for a few hundred hours due to dynamic vacuum. A surface coating with a low secondary electron yield, applied to the inner surface of an alumina tube to reduce dynamic vacuum activity without increasing the probability of Unidentified Falling Objects, and which is compatible with the high voltage environment, was included in an upgraded MKI installed in the LHC during the 2017-18 Year End Technical Stop. In addition, this MKI included an upgrade to relocate a significant portion of beam induced power from the yoke to a "damping element": this element is not at pulsed high voltage. The effectiveness of the upgrades has been demonstrated during LHC operation, hence a future version will include water cooling of the "damping element". This paper reviews dynamic vacuum around the MKIs and summarizes operational experience of the upgraded MKI