Insulin signaling in insulin resistance states and cancer: A modeling analysis

Insulin resistance is the common denominator of several diseases including type 2 diabetes and cancer, and investigating the mechanisms responsible for insulin signaling impairment is of primary importance. A mathematical model of the insulin signaling network (ISN) is proposed and used to investigate the dose-response curves of components of this network. Experimental data of C2C12 myoblasts with phosphatase and tensin homologue (PTEN) suppressed and data of L6 myotubes with induced insulin resistance have been analyzed by the model. We focused particularly on single and double Akt phosphorylation and pointed out insulin signaling changes related to insulin resistance. Moreover, a new characterization of the upstream signaling of the mammalian target of rapamycin complex 2 (mTORC2) is presented. As it is widely recognized that ISN proteins have a crucial role also in cell proliferation and death, the ISN model was linked to a cell population model and applied to data of a cell line of acute myeloid leukemia treated with a mammalian target of rapamycin inhibitor with antitumor activity. The analysis revealed simple relationships among the concentrations of ISN proteins and the parameters of the cell population model that characterize cell cycle progression and cell death

Radiative neutron capture cross section on 238U at the n_TOF CERN facility: a high precision measurement

The aim of this work is to provide a precise and accurate measurement of the 238U(n,gamma) reaction cross-section. This reaction is of fundamental importance for the design calculations of nuclear reactors, governing the behaviour of the reactor core. In particular, fast neutron reactors, which are experiencing a growing interest for their ability to burn radioactive waste, operate in the high energy region of the neutron spectrum. In this energy region inconsistencies between the existing measurements are present up to 15%, and the most recent evaluations disagree each other. In addition, the assessment of nuclear data uncertainty performed for innovative reactor systems shows that the uncertainty in the radiative capture cross-section of 238U should be further reduced to 1-3% in the energy region from 20 eV to 25 keV. To this purpose, addressed by the Nuclear Energy Agency as a priority nuclear data need, complementary experiments, one at the GELINA and two at the n_TOF facility, were scheduled within the ANDES project within the 7th Framework Project of the European Commission. The results of one of the 238U(n,gamma) measurement performed at the n_TOF CERN facility are presented in this work, carried out with a detection system constituted of two liquid scintillators. The very accurate cross section from this work is compared with the results obtained from the other measurement performed at the n_TOF facility, which exploit a different and complementary detection technique. The excellent agreement between the two data-sets points out that they can contribute to the reduction of the cross section uncertainty down to the required 1-3%

The CERN n_TOF facility: a unique tool for nuclear data measurement

The study of the resonant structures in neutron-nucleus cross-sections, and therefore of the compoundnucleus reaction mechanism, requires spectroscopic measurements to determine with high accuracy the energy of the neutron interacting with the material under study. To this purpose, the neutron time-of-flight facility n_TOF has been operating since 2001 at CERN. Its characteristics, such as the high intensity instantaneous neutron flux, the wide energy range from thermal to few GeV, and the very good energy resolution, are perfectly suited to perform highquality measurements of neutron-induced reaction cross sections. The precise and accurate knowledge of these cross sections plays a fundamental role in nuclear technologies, nuclear astrophysics and nuclear physics. Two different measuring stations are available at the n_TOF facility, called EAR1 and EAR2, with different characteristics of intensity of the neutron flux and energy resolution. These experimental areas, combined with advanced detection systems lead to a great flexibility in performing challenging measurement of high precision and accuracy, and allow the investigation isotopes with very low cross sections, or available only in small quantities, or with very high specific activity. The characteristics and performances of the two experimental areas of the n_TOF facility will be presented, together with the most important measurements performed to date and their physics case. In addition, the significant upcoming measurements will be introduced.Postprint (published version

High precision measurement of the radiative capture cross section of 238U at the n TOF CERN facility

The importance of improving the accuracy on the capture cross-section of 238U has been addressed by the Nuclear Energy Agency, since its uncertainty significantly affects the uncertainties of key design parameters for both fast and thermal nuclear reactors. Within the 7th framework programme ANDES of the European Commission three different measurements have been carried out with the aim of providing the 238U(n, gamma) cross-section with an accuracy which varies from 1 to 5%, depending on the energy range. Hereby the final results of the measurement performed at the n TOF CERN facility in a wide energy range from 1 eV to 700 keV will be presented.Postprint (published version

Radiative neutron capture cross-section measurement of ge isotopes at n_TOF CERN facility and its importance for stellar nucleosynthesis

This manuscript summarizes the results of radiative neutron capture cross-section measurements on two stable germanium isotopes, 70Ge and 73Ge. Experiments were performed at the n_TOF facility at CERN via the time-of-flight technique, over a wide neutron energy range, for all stable germanium isotopes (70,72,73,74, and 76). Results for 70Ge [Phys. Rev. C 100, 045804 (2019)] and 73Ge [Phys. Lett. B 790, 458 (2019)] are already published. In the field of nuclear structure, such measurements allow to study excited levels close to the neutron binding energy and to obtain information on nuclear properties. In stellar nucleosynthesis research, neutron induced reactions on germanium are of importance for nucleosynthesis in the weak component of the slow neutron capture processes.Peer ReviewedArticle signat per 134 autors/autores: A. Gawlik, C. Lederer-Woods, J. Andrzejewski, J. Perkowski, U. Battino, P. Ferreira, F. Gunsing, S. Heinitz, M. Krtička, C. Massimi, F. Mingrone, R. Reifarth, A. Tattersall, S. Valenta, C. Weiss, O. Aberle, L. Audouin, M. Bacak, J. Balibrea, M. Barbagallo, S. Barros, V. Bécares, F. Bečvář, C. Beinrucker, E. Berthoumieux, J. Billowes, D. Bosnar, M. Brugger, M. Caamaño, F. Calviño, M. Calviani, D. Cano-Ott, R. Cardella, A. Casanovas, D.M. Castelluccio, F. Cerutti, Y.H. Chen, E. Chiaveri, N. Colonna, G. Cortés, M.A. Cortés-Giraldo, L. Cosentino, L.A. Damone, M. Diakaki, M. Dietz, C. Domingo-Pardo, R. Dressler, E. Dupont, I. Durán, B. Fernández-Domínguez, A. Ferrari, P. Finocchiaro, V. Furman, K. Göbel, A.R. García, T. Glodariu, I.F. Gonçalves, E. González-Romero, A. Goverdovski, E. Griesmayer, C. Guerrero, H. Harada, T. Heftrich, J. Heyse, D.G. Jenkins, E. Jericha, F. Käppeler, Y. Kadi, T. Katabuchi, P. Kavrigin, V. Ketlerov, V. Khryachkov, A. Kimura, N. Kivel, I. Knapova, M. Kokkoris, E. Leal-Cidoncha, H. Leeb, J. Lerendegui-Marco, S. Lo Meo, S.J. Lonsdale, R. Losito, D. Macina, T. Martínez, P. Mastinu, M. Mastromarco, F. Matteucci, E.A. Maugeri, E. Mendoza, A. Mengoni, P.M. Milazzo, M. Mirea, S. Montesano, A. Musumarra, R. Nolte, A. Oprea, N. Patronis, A. Pavlik, J.I. Porras, J. Praena, J.M. Quesada, K. Rajeev, T. Rauscher, A. Riego-Perez, P.C. Rout, C. Rubbia, J.A. Ryan, M. Sabaté-Gilarte, A. Saxena, P. Schillebeeckx, S. Schmidt, D. Schumann, P. Sedyshev, A.G. Smith, A. Stamatopoulos, G. Tagliente, J.L. Tain, A. Tarifeño-Saldivia, L. Tassan-Got, A. Tsinganis, G. Vannini, V. Variale, P. Vaz, A. Ventura, V. Vlachoudis, R. Vlastou, A. Wallner, S. Warren, M. Weigand, C. Wolf, P.J. Woods, T. Wright, P. ŽugecObjectius de Desenvolupament Sostenible::7 - Energia Assequible i No ContaminantPostprint (author's final draft

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

First Results of the 140^{140}Ce(n,γ)141^{141}Ce Cross-Section Measurement at n_TOF

An accurate measurement of the $^{140}$Ce(n,γ) energy-dependent cross-section was performed at the n_TOF facility at CERN. This cross-section is of great importance because it represents a bottleneck for the s-process nucleosynthesis and determines to a large extent the cerium abundance in stars. The measurement was motivated by the significant difference between the cerium abundance measured in globular clusters and the value predicted by theoretical stellar models. This discrepancy can be ascribed to an overestimation of the $^{140}$Ce capture cross-section due to a lack of accurate nuclear data. For this measurement, we used a sample of cerium oxide enriched in $^{140}$Ce to 99.4%. The experimental apparatus consisted of four deuterated benzene liquid scintillator detectors, which allowed us to overcome the difficulties present in the previous measurements, thanks to their very low neutron sensitivity. The accurate analysis of the p-wave resonances and the calculation of their average parameters are fundamental to improve the evaluation of the $^{140}$Ce Maxwellian-averaged cross-section

First Results of the 140^{140}Ce(n,γ)141^{141}Ce Cross-Section Measurement at n_TOF

An accurate measurement of the $^{140}$Ce(n,γ) energy-dependent cross-section was performed at the n_TOF facility at CERN. This cross-section is of great importance because it represents a bottleneck for the s-process nucleosynthesis and determines to a large extent the cerium abundance in stars. The measurement was motivated by the significant difference between the cerium abundance measured in globular clusters and the value predicted by theoretical stellar models. This discrepancy can be ascribed to an overestimation of the $^{140}$Ce capture cross-section due to a lack of accurate nuclear data. For this measurement, we used a sample of cerium oxide enriched in $^{140}$Ce to 99.4%. The experimental apparatus consisted of four deuterated benzene liquid scintillator detectors, which allowed us to overcome the difficulties present in the previous measurements, thanks to their very low neutron sensitivity. The accurate analysis of the p-wave resonances and the calculation of their average parameters are fundamental to improve the evaluation of the $^{140}$Ce Maxwellian-averaged cross-section

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication