Recent Progress and Next Steps for the MATHUSLA LLP Detector

We report on recent progress and next steps in the design of the proposed MATHUSLA Long Lived Particle (LLP) detector for the HL-LHC as part of the Snowmass 2021 process. Our understanding of backgrounds has greatly improved, aided by detailed simulation studies, and significant R&D has been performed on designing the scintillator detectors and understanding their performance. The collaboration is on track to complete a Technical Design Report, and there are many opportunities for interested new members to contribute towards the goal of designing and constructing MATHUSLA in time for HL-LHC collisions, which would increase the sensitivity to a large variety of highly motivated LLP signals by orders of magnitude.Comment: Contribution to Snowmass 2021 (EF09, EF10, IF6, IF9), 18 pages, 12 figures. v2: included additional endorser

Essential roles for Fe65, Alzheimer's amyloid precursor binding protein, in the cellular response to DNA damage

Fe65 interacts with the cytosolic domain of the Alzheimer amyloid precursor protein (APP). The functions of the Fe65 are still unknown. To address this point we generated Fe65 knockout (KO) mice. These mice do not show any obvious phenotype; however, when fibroblasts (mouse embryonic fibroblasts), isolated from Fe65 KO embryos, were exposed to low doses of DNA damaging agents, such as etoposide or H2O2, an increased sensitivity to genotoxic stress, compared with wild type animals, clearly emerged. Accordingly, brain extracts from Fe65 KO mice, exposed to non-lethal doses of ionizing radiations, showed high levels of gamma-H2AX and p53, thus demonstrating a higher sensitivity to X-rays than wild type mice. Nuclear Fe65 is necessary to rescue the observed phenotype, and few minutes after the exposure of MEFs to DNA damaging agents, Fe65 undergoes phosphorylation in the nucleus. With a similar timing, the proteolytic processing of APP is rapidly affected by the genotoxic stress: in fact, the cleavage of the APP COOH-terminal fragments by gamma-secretase is induced soon after the exposure of cells to etoposide, in a Fe65-dependent manner. These results demonstrate that Fe65 plays an essential role in the response of the cells to DNA damage

IN INCIDENT CHRONIC DIALYSIS PATIENTS THE CHARLSON INDEX IS AN INDEPENDENT PREDICTOR OF LOW CIRCULATING PTH. AN ITALIAN MULTICENTRIC STUDY

INTRODUCTION AND AIMS: The number of elderly patients often affected by multiple comorbidities is increasingly growing in incident chronic dialysis population. However, there is a lack of knowledge about the potential nearness between such epidemiologic changes and mineral metabolism disturbances.Aim of the study was to evaluate the frequency of parathyroid and mineral metabolism disorders among incident chronic dialysis patients,correlating such changes with the comorbidity rate. METHODS: We conducted a cross-sectional observational study which involved 37 italian hemodialysis units.Each center collected data from consecutive adult patients admitted in dialysis program during the last year due to the failure of the native kidney function. We gathered data from 364 incident chronic dialysis patients(age 64 ± 15 years,65% male, 37% with diabetic and/or hypertensive nephropathy, 8% in peritoneal dialysis). The comorbidity rate was evaluated with the Charlson Index, a validate score which includes a number of chronic diseases affecting different organs. RESULTS: More than 25% of incident dialysis patients were older than seventy-five and 14.3% were older than eighty. The Charlson index was 4.01 ± 2.89. At dialysis beginning, only 27% of patients had the intact parathormone (iPTH) circulating levels ranging from 150 and 300 pg/ml, while 73% were out of such K-DOQI target range. The changes of the mineral metabolism and important parathyroid disorder conditions were far from uncommon: iPTH 500 pg/ml was present in 16.5% of patients. In less than the half of the patients, the corrected blood calcium fell within the target range 8.4 -9.5 mg/dl: 39% were above and 14% below such a blood calcium range. In addition, a phosphatemia > 5.5 mg/dl was present in 36% of cases. In those patients who presented comorbidities, the Charlson score showed a significant inverse relationship with iPTH (r -0.17, P=0.002). Further, Charlson index, age, phosphatemia, corrected calcemia and administration of vitamin D analogues were significantly and independently associated with iPTH levels (P=0.009) by multiple regression analysis. CONCLUSIONS: The incident chronic dialysis population is characterized by a high comorbidity rate and has often already severe disturbances of PTH secretion and mineral metabolism. In comorbid patients, the Charlson index was independently and significantly associated with low levels of circulating iPTH. Session: Poster: Bone and mineral metabolism - CKD -

Studies of RPC detector operation with eco-friendly gas mixtures under irradiation at the CERN Gamma Irradiation Facility

International audienceResistive Plate Chamber (RPC) detectors are widely used at the CERN LHC experiments as muon trigger thanks to their excellent time resolution. They are operated with a Freon-based gas mixture containing $C_2 H_2 F_4$ and $SF_6$, both greenhouse gases (GHG) with a very high global warming potential (GWP).The search of new environmentally friendly gas mixtures is necessary to reduce GHG emissions and costs as well as to optimize RPC performance.Several recently available gases with low GWP have been identified as possible replacements for $C_2 H_2 F_4$ and $SF_6$.In particular, eco-friendly gas mixtures based on the HFO-1234ze have been investigated on 1.4 and 2 mm single-gap and double-gap RPCs.The RPC detectors have been tested at the CERN Gamma Irradiation Facility (GIF++), which provides a high energy muon beam combined with an intense gamma source allowing to simulate the background expected at HL-LHC.The performance of RPCs were studied at different gamma rates with the new environmentally friendly gases by measuring ohmic and physics currents, fluorine radicals and HF production, rate capability and induced charge.Preliminary results on the long-term effects on the performance of the detectors are presented in this study

Test beam results and integration of the ATLAS level-1 Muon barrel trigger

The ATLAS Level-1 Muon Trigger will he crucial for the online selection of events with high transverse momentum muons and for its correct association to the bunch-crossing corresponding to the detected events. This system uses dedicated coarse granularity and fast detectors capable of providing measurements in two orthogonal projections. The Resistive Plate Chambers (RPCs) are used in the barrel region (vertical bar eta vertical bar < 1). The associated trigger electronics is based on a custom chip, the Coincidence Matrix, that performs space coincidences within programmable roads and time gates. The system is highly redundant and communicates with the ATLAS Level-1 trigger Processor with the MUCTPI Interface. The trigger electronics provides also the Readout of the RPCs. Preliminary results achieved with a full trigger tower with production detectors in the 118 test beam at CERN will he shown. In particular preliminary results on the integration of the barrel muon trigger electronics with the MUCTPI interface and with the ATLAS DAQ system will be discussed

An Update to the Letter of Intent for MATHUSLA: Search for Long-Lived Particles at the HL-LHC

We report on recent progress in the design of the proposed MATHUSLA Long Lived Particle (LLP) detector for the HL-LHC, updating the information in the original Letter of Intent (LoI), see CDS:LHCC-I-031, arXiv:1811.00927. A suitable site has been identified at LHC Point 5 that is closer to the CMS Interaction Point (IP) than assumed in the LoI. The decay volume has been increased from 20 m to 25 m in height. Engineering studies have been made in order to locate much of the decay volume below ground, bringing the detector even closer to the IP. With these changes, a 100 m x 100 m detector has the same physics reach for large c$\tau$ as the 200 m x 200 m detector described in the LoI and other studies.The performance for small c$\tau$ is improved because of the proximity to the IP. Detector technology has also evolved while retaining the strip-like sensor geometry in Resistive Plate Chambers (RPC) described in the LoI. The present design uses extruded scintillator bars read out using wavelength shifting fibers and silicon photomultipliers (SiPM). Operations will be simpler and more robust with much lower operating voltages and without the use of greenhouse gases. Manufacturing is straightforward and should result in cost savings. Understanding of backgrounds has also significantly advanced, thanks to new simulation studies and measurements taken at the MATHUSLA test stand operating above ATLAS in 2018. We discuss next steps for the MATHUSLA collaboration, and identify areas where new members can make particularly important contributions.We report on recent progress in the design of the proposed MATHUSLA Long Lived Particle (LLP) detector for the HL-LHC, updating the information in the original Letter of Intent (LoI), see CDS:LHCC-I-031, arXiv:1811.00927. A suitable site has been identified at LHC Point 5 that is closer to the CMS Interaction Point (IP) than assumed in the LoI. The decay volume has been increased from 20 m to 25 m in height. Engineering studies have been made in order to locate much of the decay volume below ground, bringing the detector even closer to the IP. With these changes, a 100 m x 100 m detector has the same physics reach for large c$\tau$ as the 200 m x 200 m detector described in the LoI and other studies. The performance for small c$\tau$ is improved because of the proximity to the IP. Detector technology has also evolved while retaining the strip-like sensor geometry in Resistive Plate Chambers (RPC) described in the LoI. The present design uses extruded scintillator bars read out using wavelength shifting fibers and silicon photomultipliers (SiPM). Operations will be simpler and more robust with much lower operating voltages and without the use of greenhouse gases. Manufacturing is straightforward and should result in cost savings. Understanding of backgrounds has also significantly advanced, thanks to new simulation studies and measurements taken at the MATHUSLA test stand operating above ATLAS in 2018. We discuss next steps for the MATHUSLA collaboration, and identify areas where new members can make particularly important contributions

Predictors of embolism and death in left-sided infective endocarditis: the European Society of Cardiology EURObservational Research Programme European Infective Endocarditis registry

International audienceBackground and Aims Even though vegetation size in infective endocarditis (IE) has been associated with embolic events (EEs) and mortality risk, it is unclear whether vegetation size associated with these potential outcomes is different in left-sided IE (LSIE). This study aimed to seek assessing the vegetation cut-off size as predictor of EE or 30-day mortality for LSIE and to determine risk predictors of these outcomes. Methods The European Society of Cardiology EURObservational Research Programme European Infective Endocarditis is a prospective, multicentre registry including patients with definite or possible IE throughout 2016–18. Cox multivariable logistic regression analysis was performed to assess variables associated with EE or 30-day mortality. Results There were 2171 patients with LSIE (women 31.5%). Among these affected patients, 459 (21.1%) had a new EE or died in 30 days. The cut-off value of vegetation size for predicting EEs or 30-day mortality was &gt;10 mm [hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.13–1.69, P = .0015]. Other adjusted predictors of risk of EE or death were as follows: EE on admission (HR 1.89, 95% CI 1.54–2.33, P &lt; .0001), history of heart failure (HR 1.53, 95% CI 1.21–1.93, P = .0004), creatinine &gt;2 mg/dL (HR 1.59, 95% CI 1.25–2.03, P = .0002), Staphylococcus aureus (HR 1.36, 95% CI 1.08–1.70, P = .008), congestive heart failure (HR 1.40, 95% CI 1.12–1.75, P = .003), presence of haemorrhagic stroke (HR 4.57, 95% CI 3.08–6.79, P &lt; .0001), alcohol abuse (HR 1.45, 95% CI 1.04–2.03, P = .03), presence of cardiogenic shock (HR 2.07, 95% CI 1.29–3.34, P = .003), and not performing left surgery (HR 1.30 95% CI 1.05–1.61, P = .016) (C-statistic = .68). Conclusions Prognosis after LSIE is determined by multiple factors, including vegetation size