High intensity neutrino oscillation facilities in Europe

The EUROnu project has studied three possible options for future, high intensity neutrino oscillation facilities in Europe. The first is a Super Beam, in which the neutrinos come from the decay of pions created by bombarding targets with a 4 MW proton beam from the CERN High Power Superconducting Proton Linac. The far detector for this facility is the 500 kt MEMPHYS water Cherenkov, located in the Fréjus tunnel. The second facility is the Neutrino Factory, in which the neutrinos come from the decay of μ+ and μ− beams in a storage ring. The far detector in this case is a 100 kt magnetized iron neutrino detector at a baseline of 2000 km. The third option is a Beta Beam, in which the neutrinos come from the decay of beta emitting isotopes, in particular He6 and Ne18, also stored in a ring. The far detector is also the MEMPHYS detector in the Fréjus tunnel. EUROnu has undertaken conceptual designs of these facilities and studied the performance of the detectors. Based on this, it has determined the physics reach of each facility, in particular for the measurement of CP violation in the lepton sector, and estimated the cost of construction. These have demonstrated that the best facility to build is the Neutrino Factory. However, if a powerful proton driver is constructed for another purpose or if the MEMPHYS detector is built for astroparticle physics, the Super Beam also becomes very attractive

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Disorders of sex development: effect of molecular diagnostics

Disorders of sex development (DSDs) are a diverse group of conditions that can be challenging to diagnose accurately using standard phenotypic and biochemical approaches. Obtaining a specific diagnosis can be important for identifying potentially life-threatening associated disorders, as well as providing information to guide parents in deciding on the most appropriate management for their child. Within the past 5 years, advances in molecular methodologies have helped to identify several novel causes of DSDs; molecular tests to aid diagnosis and genetic counselling have now been adopted into clinical practice. Occasionally, genetic profiling of embryos prior to implantation as an adjunct to assisted reproduction, prenatal diagnosis of at-risk pregnancies and confirmatory testing of positive results found during newborn biochemical screening are performed. Of the available genetic tests, the candidate gene approach is the most popular. New high-throughput DNA analysis could enable a genetic diagnosis to be made when the aetiology is unknown or many differential diagnoses are possible. Nonetheless, concerns exist about the use of genetic tests. For instance, a diagnosis is not always possible even using new molecular approaches (which can be worrying for the parents) and incidental information obtained during the test might cause anxiety. Careful selection of the genetic test indicated for each condition remains important for good clinical practice. The purpose of this Review is to describe advances in molecular biological techniques for diagnosing DSDs

High Power Molten Targets for Radioactive Ion Beam Production: from Particle Physics to Medical Applications

Megawatt-class molten targets, combining high material densities and good heat transfer properties are being considered for neutron spallation sources, neutrino physics facilities and radioactive ion beam production. For this last category of facilities, in order to cope with the limitation of long diffusion times affecting the extraction of short-lived isotopes, a lead-bismuth eutectic (LBE) target loop equipped with a diffusion chamber has been proposed and tested offline during the EURISOL design study. To validate the concept, a molten LBE loop is now in the design phase and will be prototyped and tested on-line at CERN-ISOLDE. This concept was further extended to an alternative route to produce 1013 18Ne/s for the Beta Beams, where a molten salt loop would be irradiated with 7 mA, 160 MeV proton beam. Some elements of the concept have been tested by using a molten fluoride salt static unit at CERNISOLDE. The investigation of the release and production of neon isotopes allowed the measurement of the diffusion coefficient of this element in molten fluoride salts

The dolutegravir/valproic acid drug-drug interaction is primarily based on protein displacement

Objectives: The dolutegravir/valproic acid drug-drug interaction (DDI) is suggested to be caused by protein displacement. Here, we assess the underlying mechanism. Methods: Participants in a randomized controlled trial investigating valproic acid as an HIV latency reversing agent were recruited in a predefined pharmacokinetic substudy if they were on once-daily 50 mg dolutegravir-containing combination ART (cART) for >12 months with a plasma HIV-RNA <50 copies/mL (trial registration: ClinicalTrials.gov NCT03525730). Participants were randomized to receive 30 mg/kg/day valproic acid orally (divided into two equal doses) for 14 days or not. Total and unbound dolutegravir concentrations were measured on day 0 (before intake of valproic acid and 6 h after intake of valproic acid) and on days 1, 7, 14 and 42. Intra- and inter-subject dolutegravir concentrations and geometric means (GMs) were evaluated. Results: Six of 10 participants on dolutegravir were randomized to receive valproic acid. During 14 days of valproic acid treatment, the GM total dolutegravir concentration decreased sharply from 1.36 mg/L on day 0 to 0.85, 0.31 and 0.20 mg/L on days 0, 1, 7 and 14, respectively, while total dolutegravir concentrations in the controls remained comparable during the same period: 1.27-1.49 mg/L. We observed a parallel increase in unbound dolutegravir fractions ranging from 0.39% to 0.58% during valproic acid administration, compared with 0.25% to 0.28% without valproic acid. Unbound dolutegravir concentrations were above the established in vitro EC90 value for unbound dolutegravir in 85% of the tested samples. Conclusions: This study confirms protein displacement as the main mechanism for this DDI, although additional mechanisms might be involved too. If dolutegravir is taken with food, this DDI is probably not clinically relevant

Beta beams: an accelerator-based facility to explore neutrino oscillation physics

International audience

Beta beams:An accelerator based facility to explore neutrino oscillation physics

The discovery that the neutrino changes flavor as it travels through space has implications for the Standard Model of particle physics (SM)[1]. To know the contribution of neutrinos to the SM, needs precise measurements of the parameters governing the neutrino oscillations. This will require a high intensity beam-based neutrino oscillation facility. The EUROν Design Study will review three currently accepted methods of realizing this facility (the so-called Super-Beams, Beta Beams and Neutrino Factories) and perform a cost assessment that, coupled with the physics performance, will give means to the European research authorities to make a decision on the lay-out and construction of the future European neutrino oscillation facility. "Beta Beams" produce collimated pure electron neutrino and antineutrino beams by accelerating beta active ions to high energies and letting them decay in a race-track shaped storage ring. EUROν Beta Beams are based on CERNs infrastructure and the fact that some of the already existing accelerators can be used. To use existing machines is a strong advantage for the cost evaluation, however this choice is also constraining the Beta Beams. In this article we describe recent work that has made the Beta Beam facility a solid option for neutrino production: new ideas and developments to produce and collect different Beta Beam isotopes, the 60 GHz pulsed ECR source development, the integration of Beta Beams in the upgrade program for LHC, work to ensure the very high intensity ion beam stability in the different machines, and optimizations of the decay ring to get high neutrino flux at a gamma boost of 100

Beta beams for precision measurements of neutrino oscillation parameters

Neutrino oscillations have implications for the Standard Model of particle physics. The CERN Beta Beam has outstanding capabilities to contribute to precision measurements of the parameters governing neutrino oscillations. The FP7 collaboration EUROnu (2008-2012) is a design study that will review three facilities (Super-Beams, Beta Beams and Neutrino Factories) and perform a cost assessment that, coupled with the physics performance, will give means to the European research authorities to make decisions on future European neutrino oscillation facilities. "Beta Beams" produce collimated pure electron (anti)neutrinos by accelerating beta active ions to high energies and having them decay in a storage ring. Using existing machines and infrastructure is an advantage for the cost evaluation; however, this choice is also constraining the Beta Beams. Recent work to make the Beta Beam facility a solid option will be described: production of Beta Beam isotopes, the 60 GHz pulsed ECR source development, integration into the LHC-upgrades, insure the high intensity ion beam stability, and optimizations to get high neutrino fluxes. The costing approach will also be described

Design of a neutrino source based on beta beams

``Beta beams'' produce collimated pure electron (anti)neutrino beams by accelerating beta active ions to high energies and having them decay in a racetrack shaped storage ring of 7 km circumference, the decay ring. EUROnu beta beams are based on CERN infrastructures and existing machines. Using existing machines may be an advantage for the cost evaluation, but will also constrain the physics performance. The isotope pair of choice for the beta beam is $^{6}\mathrm{He}$ and $^{18}\mathrm{Ne}$. However, before the EUROnu studies one of the required isotopes, $^{18}\mathrm{Ne}$, could not be produced in rates that satisfy the needs for physics of the beta beam. Therefore, studies of alternative beta emitters, $^{8}\mathrm{Li}$ and $^{8}\mathrm{B}$, with properties interesting for a beta beam have been proposed and have been studied within EUROnu. These alternative isotopes could be produced by using a small storage ring, in which the beam traverses a target, creating the $^{8}\mathrm{Li}$ and $^{8}\mathrm{B}$ isotopes. This production ring, the injection linac and the target system have been evaluated. Measurements of the cross section of the reactions to produce the beta beam isotopes show interesting results. A device to collect the produced isotopes from the target has been developed and tested. However, the yields of $^{8}\mathrm{Li}$ and $^{8}\mathrm{B}$, using the production ring for production of $^{8}\mathrm{Li}$ and $^{8}\mathrm{B}$, is not yet, according to simulations, giving the rates of isotopes that would be needed. Therefore, a new method of producing the $^{18}\mathrm{Ne}$ isotope has been developed and tested giving good production rates. A 60 GHz ECRIS prototype, the first in the world, was developed and tested for ion production with contributions from EUROnu. The decay ring lattices for the $^{8}\mathrm{Li}$ and $^{8}\mathrm{B}$ have been developed and the lattice for $^{6}\mathrm{He}$ and $^{18}\mathrm{Ne}$ has been optimized to ensure the high intensity ion beam stability