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The CERN Proton Synchrotron booster (PSB) is one of the machines of the LHC injector chain which will be upgraded within the LHC Injectors Upgrade (LIU) project. The injection energy of the PSB will be increased to 160 MeV in order to mitigate direct space charge effects, considered to be the main performance limitation, aiming to double the brightness for the LHC beams. In order to better predict the gain to be expected, space charge simulations are being carried out. As a first step, benchmarking between simulations and measurements is needed. Efforts to establish a realistic modeling of field and alignment errors aim at extending the basic model of the machine toward a more realistic one. Simulations of beam dynamics with strong space charge and realistic errors are presented and analyzed in this paper.

The properties of the neutrino provide a unique window on physics beyond that described by the standard model. The study of subleading effects in neutrino oscillations, and the race to discover CP-invariance violation in the lepton sector, has begun with the recent discovery that θ_{13}>0. The measured value of θ_{13} is large, emphasizing the need for a facility at which the systematic uncertainties can be reduced to the percent level. The neutrino factory, in which intense neutrino beams are produced from the decay of muons, has been shown to outperform all realistic alternatives and to be capable of making measurements of the requisite precision. Its unique discovery potential arises from the fact that only at the neutrino factory is it practical to produce high-energy electron (anti)neutrino beams of the required intensity. This paper presents the conceptual design of the neutrino factory accelerator facility developed by the European Commission Framework Programme 7 EUROν Design Study consortium. EUROν coordinated the European contributions to the International Design Study for the Neutrino Factory (the IDS-NF) collaboration. The EUROν baseline accelerator facility will provide 10^{21} muon decays per year from 12.6 GeV stored muon beams serving a single neutrino detector situated at a source-detector distance of between 1 500 km and 2 500 km. A suite of near detectors will allow definitive neutrino-scattering experiments to be performed.

“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}He and ^{18}Ne. However, before the EUROnu studies one of the required isotopes, ^{18}Ne, could not be produced in rates that satisfy the needs for physics of the beta beam. Therefore, studies of alternative beta emitters, ^{8}Li and ^{8}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}Li and ^{8}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}Li and ^{8}B, using the production ring for production of ^{8}Li and ^{8}B, is not yet, according to simulations, giving the rates of isotopes that would be needed. Therefore, a new method of producing the ^{18}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}Li and ^{8}B have been developed and the lattice for ^{6}He and ^{18}Ne has been optimized to ensure the high intensity ion beam stability.

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 ^{6}He and ^{18}Ne, 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.

The electron cloud may cause transverse single-bunch instabilities of proton beams such as those in the Large Hadron Collider (LHC) and the CERN Super Proton Synchrotron (SPS). We simulate these instabilities and the consequent emittance growth with the code HEADTAIL, which models the turn-by-turn interaction between the cloud and the beam. Recently some new features were added to the code, in particular, electric conducting boundary conditions at the chamber wall, transverse feedback, and variable beta functions. The sensitivity to several numerical parameters has been studied by varying the number of interaction points between the bunch and the cloud, the phase advance between them, and the number of macroparticles used to represent the protons and the electrons. We present simulation results for both LHC at injection and SPS with LHC-type beam, for different electron-cloud density levels, chromaticities, and bunch intensities. Two regimes with qualitatively different emittance growth are observed: above the threshold of the transverse mode-coupling (TMC) type of instability there is a rapid blowup of the beam, while below this threshold a slow, long-term, emittance growth remains. The rise time of the TMC instability caused by the electron cloud is compared with results obtained using an equivalent broadband resonator impedance model, demonstrating reasonable agreement.

We review the dynamics of a bouncing ball, both from the classical and the quantum points of view, studying the role of its inertial and gravitational masses. We analyze the behavior of quantum particles of different masses, embedded in a uniform gravitational field. We show that the bouncing ball is a useful didactic example to show that the coupling between rest mass and gravity cannot be avoided at the quantum level and that the equivalence principle must be reformulated in quantum mechanics. Galileo’s experiment of falling bodies can be still satisfied if one considers only the average quantum values of observables. [ABSTRACT FROM AUTHOR]

We want to shed light on some discussed aspects of the principle of equivalence. We consider two different phases in the evolution of the principle. We pay attention to the fact that some textbooks do not dwell on the mathematical meaning of ‘locally flat spacetime’, which can confuse students and, occasionally, can also lead to misinterpretations. For example, the non-eliminability of tidal forces, not even locally, may suggest that the equivalence principle is wrong. By contrast, we want to show that this is in perfect agreement with the Einstein geometrical interpretation of spacetime. Finally, in order to check the approximations used in the Gedankenexperiment of an elevator, we estimate explicitly the magnitude of the deflection of light and the effects of tidal forces in a ‘real lift’. [ABSTRACT FROM AUTHOR]

The aim of this paper is to make a determination of Hubble’s constant from the experimental data on the magnitude and redshift of supernovae. We proposed a very simple approach that could also be very useful from a didactic point of view. [ABSTRACT FROM AUTHOR]

Dietary interventions represent an interesting alternative to pharmacological treatments for improving the quality of life (QoL) of subjects suffering from gastroesophageal reflux disease (GERD). This randomized, double-blind, placebo-controlled study aimed to evaluate the efficacy of a food supplement (FS) containing a probiotic strain, bioactive peptides, and vitamins in relieving heartburn/dyspeptic symptoms in subjects with mild-to-moderate GERD. Fifty-six adult participants were randomly assigned to receive the placebo or the active FS for 28 days. Subjects were asked to record daily the frequency and intensity of heartburn episodes and the intake of over- the-counter (OTC) medications. GERD-QoL and self-assessment questionnaires were also completed every two weeks and at the end of the treatment, respectively. FS was effective in achieving a progressive and significant reduction of heartburn frequency and severity, with an intergroup significant difference at the end of the treatment period. FS group also reported a reduction in the OTC medication intake, whereas placebo administration did not modify the OTC intake. Results from the QoL and self-assessment questionnaires showed that FS administration achieved a progressive and statistically significant intragroup and intergroup improvement in the QoL score and a higher positive response with respect to the placebo treatment.

Background: Although proton pump inhibitor (PPI) drugs have considered able to induce small intestinal bacterial overgrowth (SIBO), no data are so far available from primary care (PC). We assessed the prevalence of SIBO and methane (CH4) production consequent to chronic PPI therapy using Lactulose Breath Test (LBT). Secondary aim was to explore the possible role of rifaximin in treating PPI-induced SIBO patients., Methods: One hundred twenty-five gastroesophageal reflux disease patients, constantly treated with PPI for at least 6 months and undergoing to LBT, were retrospectively assessed. An age-matched control population (control) of 100 patients, which had not used PPI in the last 6 months, was also enrolled. In the PPI group, SIBO positive patients and CH4 producers were treated with rifaximin 1200 mg/daily for 14 days and re-checked with LBT one month after the end of treatment. The area under the curve (AUC) before and after treatment was also calculated for both SIBO positive patients and CH4 producers., Results: In the PPI group, SIBO prevalence was significantly higher vs. controls (38/125 [30.4%] vs. 27/100 [27%], P<0.05). 77/125 (61.6%) PPI patients were found to be CH4 producers vs. 21/100 (21%) controls (P<0.05). Among SIBO patients in the PPI group, 34 (89.4%) were also CH4 producers vs. 17/27 (63%) controls (P<0.05). After treatment, LBT resulted negative in 15/22 SIBO patients (68.1%) (P<0.05) and in 18/34 CH4 producers (52.9%) (P<0.05). At the AUC analysis, an overall reduction of 54.2% for H2 in SIBO patients and of 47.7% for CH4 was assessed after rifaximin treatment (P<0.05)., Conclusions: Our data showed that chronic use of PPI could be able to increase the prevalence of SIBO and to shift the intestinal microbial composition towards a CH4-producing flora. rifaximin could represent a useful therapeutical option for PPI-induced SIBO and for modulating CH4-producing flora.

Irritable bowel syndrome (IBS) guidelines are generally developed by experts, with the possibility of a translational gap in clinical medicine. The aim of our study was to assess an Italian group of general practitioners (GPs) for their awareness and use of criteria for the diagnosis and management of IBS. For this purpose, a survey was carried out involving 235 GPs, divided into two groups according to their years of activity: 65 “junior general practitioners” (JGPs) (≤10 years) and 170 “senior general practitioners” (SGPs) (>10 years). JGPs were more familiar with the Rome IV Criteria and Bristol Scale than SGPs. Abdominal pain, bowel movement frequency and bloating were the symptoms most frequently used to make a diagnosis. The most probable causes of IBS were reported to be abnormal gastrointestinal motility and psychological triggers. SGPs reported more frequently than JGPs that challenging management and patient’s request were motivations for a gastroenterological consultation. The practice of clinical medicine is still far from the guidelines provided by the specialists. Abdominal pain related to defecation and changes in bowel frequency are considered to be the more important symptoms for IBS diagnosis, but most GPs, both JGPs and SGPs, like to consider abdominal bloating as another useful symptom. Involving both gastroenterologists and GPs in developing shared guidelines would be highly desirable in order to improve IBS management strategies in everyday clinical practice.

Aims: Stress echocardiography is widely used to identify obstructive coronary artery disease (CAD). High accuracy is reported in expert hands but is dependent on operator training and image quality. The EVAREST study provides UK-wide data to evaluate real-world performance and accuracy of stress echocardiography., Methods and Results: Participants undergoing stress echocardiography for CAD were recruited from 31 hospitals. Participants were followed up through health records which underwent expert adjudication. Cardiac outcome was defined as anatomically or functionally significant stenosis on angiography, revascularization, medical management of ischaemia, acute coronary syndrome, or cardiac-related death within 6 months. A total of 5131 patients (55% male) participated with a median age of 65 years (interquartile range 57-74). 72.9% of studies used dobutamine and 68.5% were contrast studies. Inducible ischaemia was present in 19.3% of scans. Sensitivity and specificity for prediction of a cardiac outcome were 95.4% and 96.0%, respectively, with an accuracy of 95.9%. Sub-group analysis revealed high levels of predictive accuracy across a wide range of patient and protocol sub-groups, with the presence of a resting regional wall motion abnormalitiy significantly reducing the performance of both dobutamine (P < 0.01) and exercise (P < 0.05) stress echocardiography. Overall accuracy remained consistently high across all participating hospitals., Conclusion: Stress echocardiography has high accuracy across UK-based hospitals and thus indicates stress echocardiography is being delivered effectively in real-world practice, reinforcing its role as a first-line investigation in the assessment of patients with stable chest pain., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Implementation: Novel coronavirus disease 2019 (COVID-19) has presented unique challenges for patients and health care systems, including a surge in behavioral health (BH) needs. A community teaching public hospital system in Massachusetts (MA) whose 13 primary care (PC) clinics serve a diverse patient population, has developed a model for Primary Care Behavioral Health Integration (PCBHI) to provide brief, evidence-based interventions to patients in PC. In response to COVID-19, the system developed an intensive community management strategy to care for patients with COVID-19 outside of the hospital, and its PCBHI program adapted alongside this strategy to provide rapid support to patients in emotional distress. Over a 13-week period, 78 patients were specifically referred to the PCBHI COVID clinic and received rapid therapeutic support and/or care navigation. Recommendations: This article will discuss the development and implementation of the PCBHI COVID clinic, common presenting issues and clinical interventions used, and lessons that informed our adaptation of clinic operations and that can serve as recommendations to other health systems in establishing similar services. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background: The relationship between aliments and pathophysiological abnormalities leading to gastroesophageal reflux disease (GERD) symptoms elicitation is unclear. Nevertheless, patients often report symptoms after ingestion of specific foods., Aims: To identify in primary care setting the presence of foods able to trigger GERD symptoms, and evaluate whether a consequent specific food elimination diet may result in clinical improvement., Methods: Diagnosis of GERD and quantification of reflux symptoms were done according to GERD-Q questionnaire (positive when > 8). During clinical data collection, patients were asked to report aliments associated with their symptoms. Also, a precompiled list of additional foods was administered to them. Then, patients were requested to eliminate the specific foods identified, and to come back for follow-up visit after 2 weeks when GERD-Q questionnaire and clinical data collection were repeated., Results: One-hundred GERD (mean GERD-Q score 11.6) patients (54 females, mean age 48.7 years) were enrolled. Eighty-five patients reported at least one triggering food, mostly spicy foods (62%), chocolate (55%), pizza (55%), tomato (52%), and fried foods (52%). At follow-up visit, the diagnosis of GERD was confirmed in only 55 patients, and the mean GERD-Q score decreased to 8.9. Heartburn reporting decreased from 93 to 44% of patients, while regurgitation decreased from 72 to 28%. About half of the patients agreed to continue with only dietary recommendations., Conclusions: Most patients with GERD can identify at least one food triggering their symptoms. An approach based on abstention from identified food may be effective in the short term.

Introduction: Healthcare delivery is being transformed by COVID-19 to reduce transmission risk but continued delivery of routine clinical tests is essential. Stress echocardiography is one of the most widely used cardiac tests in the NHS. We assessed the impact of the first (W1) and second (W2) waves of the pandemic on the ability to deliver stress echocardiography., Methods: Clinical echocardiography teams in 31 NHS hospitals participating in the EVAREST study were asked to complete a survey on the structure and delivery of stress echocardiography as well as its impact on patients and staff in July and November 2020. Results were compared to stress echocardiography activity in the same centre during January 2020., Results: 24 completed the survey in July, and 19 NHS hospitals completed the survey in November. A 55% reduction in the number of studies performed was reported in W1, recovering to exceed pre-COVID rates in W2. The major change was in the mode of stress delivery. 70% of sites stopped their exercise stress service in W1, compared to 19% in W2. In those still using exercise during W1, 50% were wearing FFP3/N95 masks, falling to 38% in W2. There was also significant variability in patient screening practices with 7 different pre-screening questionnaires used in W1 and 6 in W2., Conclusion: Stress echocardiography delivery restarted effectively after COVID-19 with adaptations to reduce transmission that means activity has been able to continue, and exceed, pre-COVID-19 levels during the second wave. Further standardization of protocols for patient screening and PPE may help further improve consistency of practice within the United Kingdom.

Objective: Symptomatic uncomplicated diverticular disease of the colon (SUDD) is generally managed by gastroenterologists rather than General Practitioners (GPs). The aim of this study was to assess the efficacy of the treatment of SUDD with rifaximin, a non-absorbable antibiotic, in a primary care setting by GPs., Patients and Methods: This retrospective, observational study investigated the use of rifaximin at a dose of 400 mg b.i.d. for 5, 7 or 10 days monthly, up to 3 months. The symptoms were reported by the patients using a visual analogic scale (VAS) of 0-10., Results: 286 SUDD patients were enrolled (44.4% of men, average age 70.92±10.98). Respectively, 15 (5.2%) patients received the treatment for 5 days, 205 (71.7%) for 7 days and 66 (23.1%) for 10 days. After three months, a significant reduction of VAS score was observed in almost all symptoms assessed: 135 (47.2%) patients reported no abdominal pain (p<0.001) and 23 (8.1%) reported no symptom. Adverse events related to the treatment were recorded in 3 (1.04%) patients, all of them mild and not requiring interruption of the treatment. Acute diverticulitis occurred in 9 (3.1%) patients, but only 2 of them [0.7% (n=2)] underwent surgery due to complicated diverticulitis. Analysis within the different treatment groups (5, 7 and 10 days) shows that rifaximin treatment is effective in reducing the severity of symptoms in almost all groups except for the constipation in the 5-day group., Conclusions: Rifaximin can be effectively used by GPs in real-life for the management of SUDD.

We identified and compared secreted microRNA (miRNA) expression in aqueous humor (AH) and plasma samples among patients with: type 2 diabetes mellitus (T2D) complicated by non-proliferative diabetic retinopathy (DR) associated with diabetic macular edema (DME) (DME group: 12 patients); T2D patients without DR (D group: 8 patients); and non-diabetic patients (CTR group: 10 patients). Individual patient AH samples from five subjects in each group were profiled on TaqMan Low Density MicroRNA Array Cards. Differentially expressed miRNAs identified from profiling were then validated in single assay for all subjects. The miRNAs validated in AH were then evaluated in single assay in plasma. Gene Ontology (GO) analysis was conducted. From AH profiling, 119 mature miRNAs were detected: 86 in the DME group, 113 in the D group and 107 in the CTR group. miRNA underexpression in the DME group was confirmed in single assay for let-7c-5p, miR-200b-3p, miR-199a-3p and miR-365-3p. Of these four, miR-199a-3p and miR-365-3p were downregulated also in the plasma of the DME group. GO highlighted 54 validated target genes of miR-199a-3p, miR-200b-3p and miR-365-3p potentially implied in DME pathogenesis. Although more studies are needed, miR-200b-3p, let-7c-5p, miR-365-3p and miR-199a-3p represent interesting molecules in the study of DME pathogenesis., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.