Hamiltonian Noether theorem for gauge systems and two time physics

The Noether theorem for Hamiltonian constrained systems is revisited. In particular, our review presents a novel method to show that the gauge transformations are generated by the conserved quantities associated with the first class constraints. We apply our results to the relativistic point particle, to the Friedberg et al. model and, with special emphasis, to two time physics.Comment: 20 pages, Latex, references added, the "massless" sense of (87) is clarifie

A beam-beam monitoring detector for the MPD experiment at NICA

The Multi-Purpose Detector (MPD) is to be installed at the Nuclotron Ion Collider fAcility (NICA) of the Joint Institute for Nuclear Research (JINR). Its main goal is to study the phase diagram of the strongly interacting matter produced in heavy-ion collisions. These studies, while providing insight into the physics of heavy-ion collisions, are relevant for improving our understanding of the evolution of the early Universe and the formation of neutron stars. In order to extend the MPD trigger capabilities, we propose to include a high granularity beam-beam monitoring detector (BE-BE) to provide a level-0 trigger signal with an expected time resolution of 30 ps. This new detector will improve the determination of the reaction plane by the MPD experiment, a key measurement for flow studies that provides physics insight into the early stages of the reaction. In this work, we use simulated Au+Au collisions at NICA energies to show the potential of such a detector to determine the event plane resolution, providing further redundancy to the detectors originally considered for this purpose namely, the Fast Forward Detector (FFD) and the Hadron Calorimeter (HCAL). We also show our results for the time resolution studies of two prototype cells carried out at the T10 beam line at the CERN PS complex.Comment: 16 pages, 12 figures. Updated to published version with added comments and correction

Efficacy and safety of preoperative preparation with Lugol''s iodine solution in euthyroid patients with Graves’ disease (LIGRADIS Trial): Study protocol for a multicenter randomized trial

Background: Currently, both the American Thyroid Association and the European Thyroid Association recommend preoperative preparation with Lugol''s Solution (LS) for patients undergoing thyroidectomy for Graves’ Disease (GD), but their recommendations are based on low-quality evidence. The LIGRADIS trial aims to provide evidence either to support or refute the systematic use of LS in euthyroid patients undergoing thyroidectomy for GD. Methods: A multicenter randomized controlled trial will be performed. Patients =18 years of age, diagnosed with GD, treated with antithyroid drugs, euthyroid and proposed for total thyroidectomy will be eligible for inclusion. Exclusion criteria will be prior thyroid or parathyroid surgery, hyperparathyroidism that requires associated parathyroidectomy, thyroid cancer that requires adding a lymph node dissection, iodine allergy, consumption of lithium or amiodarone, medically unfit patients (ASA-IV), breastfeeding women, preoperative vocal cord palsy and planned endoscopic, video-assisted or remote access surgery. Between January 2020 and January 2022, 270 patients will be randomized for either receiving or not preoperative preparation with LS. Researchers will be blinded to treatment assignment. The primary outcome will be the rate of postoperative complications: hypoparathyroidism, recurrent laryngeal nerve injury, hematoma, surgical site infection or death. Secondary outcomes will be intraoperative events (Thyroidectomy Difficulty Scale score, blood loss, recurrent laryngeal nerve neuromonitoring signal loss), operative time, postoperative length of stay, hospital readmissions, permanent complications and adverse events associated to LS. Conclusions: There is no conclusive evidence supporting the benefits of preoperative treatment with LS in this setting. This trial aims to provide new insights into future Clinical Practice Guidelines recommendations. Trial registration: ClinicalTrials.gov identifier: NCT03980132. © 202

Azokh caves excavations 2002-2006: Middle-Upper palaeolithic transition in Nagorno-Karabagh

Depto. de Geodinámica, Estratigrafía y PaleontologíaFac. de Ciencias GeológicasTRUEpu

Impact of biological agents on postsurgical complications in inflammatory bowel disease: A multicentre study of Geteccu

Background: The impact of biologics on the risk of postoperative complications (PC) in inflammatory bowel disease (IBD) is still an ongoing debate. This lack of evidence is more relevant for ustekinumab and vedolizumab. Aims: To evaluate the impact of biologics on the risk of PC. Methods: A retrospective study was performed in 37 centres. Patients treated with biologics within 12 weeks before surgery were considered “exposed”. The impact of the exposure on the risk of 30-day PC and the risk of infections was assessed by logistic regression and propensity score-matched analysis. Results: A total of 1535 surgeries were performed on 1370 patients. Of them, 711 surgeries were conducted in the exposed cohort (584 anti-TNF, 58 vedolizumab and 69 ustekinumab). In the multivariate analysis, male gender (OR: 1.5; 95% CI: 1.2–2.0), urgent surgery (OR: 1.6; 95% CI: 1.2–2.2), laparotomy approach (OR: 1.5; 95% CI: 1.1–1.9) and severe anaemia (OR: 1.8; 95% CI: 1.3–2.6) had higher risk of PC, while academic hospitals had significantly lower risk. Exposure to biologics (either anti-TNF, vedolizumab or ustekinumab) did not increase the risk of PC (OR: 1.2; 95% CI: 0.97–1.58), although it could be a risk factor for postoperative infections (OR 1.5; 95% CI: 1.03–2.27). Conclusions: Preoperative administration of biologics does not seem to be a risk factor for overall PC, although it may be so for postoperative infections

Gaia Focused Product Release: Radial velocity time series of long-period variables

The third Gaia Data Release (DR3) provided photometric time series of more than 2 million long-period variable (LPV) candidates. Anticipating the publication of full radial-velocity (RV) in DR4, this Focused Product Release (FPR) provides RV time series for a selection of LPVs with high-quality observations. We describe the production and content of the Gaia catalog of LPV RV time series, and the methods used to compute variability parameters published in the Gaia FPR. Starting from the DR3 LPVs catalog, we applied filters to construct a sample of sources with high-quality RV measurements. We modeled their RV and photometric time series to derive their periods and amplitudes, and further refined the sample by requiring compatibility between the RV period and at least one of the $G$, $G_{\rm BP}$, or $G_{\rm RP}$ photometric periods. The catalog includes RV time series and variability parameters for 9\,614 sources in the magnitude range $6\lesssim G/{\rm mag}\lesssim 14$, including a flagged top-quality subsample of 6\,093 stars whose RV periods are fully compatible with the values derived from the $G$, $G_{\rm BP}$, and $G_{\rm RP}$ photometric time series. The RV time series contain a mean of 24 measurements per source taken unevenly over a duration of about three years. We identify the great most sources (88%) as genuine LPVs, with about half of them showing a pulsation period and the other half displaying a long secondary period. The remaining 12% consists of candidate ellipsoidal binaries. Quality checks against RVs available in the literature show excellent agreement. We provide illustrative examples and cautionary remarks. The publication of RV time series for almost 10\,000 LPVs constitutes, by far, the largest such database available to date in the literature. The availability of simultaneous photometric measurements gives a unique added value to the Gaia catalog (abridged)Comment: 36 pages, 38 figure

Role of age and comorbidities in mortality of patients with infective endocarditis

Purpose: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. Methods: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015. Patients were stratified into three age groups:<65 years, 65 to 80 years, and = 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. Results: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 = 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients =80 years who underwent surgery were significantly lower compared with other age groups (14.3%, 65 years; 20.5%, 65-79 years; 31.3%, =80 years). In-hospital mortality was lower in the <65-year group (20.3%, <65 years;30.1%, 65-79 years;34.7%, =80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%, =80 years; p = 0.003).Independent predictors of mortality were age = 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI = 3 (HR:1.62; 95% CI:1.39–1.88), and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared, the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. Conclusion: There were no differences in the clinical presentation of IE between the groups. Age = 80 years, high comorbidity (measured by CCI), and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Association of a single nucleotide polymorphism combination pattern of the Klotho gene with non-cardiovascular death in patients with chronic kidney disease

Chronic kidney disease (CKD) is associated with an elevated risk of all-cause mortality, with cardiovascular death being extensively investigated. However, non-cardiovascular mortality represents the biggest percentage, showing an evident increase in recent years. Klotho is a gene highly expressed in the kidney, with a clear influence on lifespan. Low levels of Klotho have been linked to CKD progression and adverse outcomes. Single nucleotide polymorphisms (SNPs) of the Klotho gene have been associated with several diseases, but studies investigating the association of Klotho SNPs with noncardiovascular death in CKD populations are lacking. The main aim of this study was to assess whether 11 Klotho SNPs were associated with non-cardiovascular death in a subpopulation of the National Observatory of Atherosclerosis in Nephrology (NEFRONA) study (n ¼ 2185 CKD patients). After 48 months of follow-up, 62 cardiovascular deaths and 108 non-cardiovascular deaths were recorded. We identified a high non-cardiovascular death risk combination of SNPs corresponding to individuals carrying the most frequent allele (G) at rs562020, the rare allele (C) at rs2283368 and homozygotes for the rare allele (G) at rs2320762 (rs562020 GG/AG þ rs2283368 CC/CT þ rs2320762 GG). Among the patients with the three SNPs genotyped (n ¼ 1016), 75 (7.4%) showed this combination. Furthermore, 95 (9.3%) patients showed a low-risk combination carrying all the opposite genotypes (rs562020 AA þ rs2283368 TT þ rs2320762 GT/TT). All the other combinations [n ¼ 846 (83.3%)] were considered as normal risk. Using competing risk regression analysis, we confirmed that the proposed combinations are independently associated with a higher fhazard ratio [HR] 3.28 [confidence interval (CI) 1.51-7.12]g and lower [HR 6 × 10- (95% CI 3.3 × 10--1.1 × 10-)] risk of suffering a non-cardiovascular death in the CKD population of the NEFRONA cohort compared with patients with the normal-risk combination. Determination of three SNPs of the Klotho gene could help in the prediction of non-cardiovascular death in CKD