Serotype epidemiology and multidrug resistance patterns of Salmonella enterica infecting humans in Italy

BACKGROUND: Salmonella enterica is the zoonotic agent most frequently responsible for foodborne infections in humans worldwide. In this work the presence of S. enterica was investigated in 734 unique enteropathogenic isolates collected from human patients between 2011 and 2012. RESULTS: All Salmonella spp. isolates were subjected to serotyping and antimicrobial susceptibility testing. Isolates displaying phenotypes and antimicrobial susceptibility profiles different from the reference strains were genotipically characterized. Several plasmid-embedded resistance determinants were identified and characterized. Non-typhoidal serotypes were most frequently diagnosed; monophasic Salmonella typhimurium 1,4 [5],12:i- and S. typhimurium represented the most prevalent serovars. Five isolates displayed phenotypes with extremely reduced susceptibility to antimicrobials: we detected multidrug resistance elements belonging to Ambler class A and class C in two non-typhoidal S. enterica serovars, i.e. Rissen and monophasic S. typhimurium 1,4 [5],12:i-, and in one typhoidal serovar, i.e., Paratyphi B. These resistance determinants have been so far almost exclusively associated with non-Salmonella members of the Enterobacteriaceae family. Alarmingly, two colistin resistant Salmonella enteritidis were also found. CONCLUSIONS: This work draws the attention to the still low, but rising, percentage of multidrug resistant Salmonella isolates infecting humans in Italy. Our results suggest that prompt monitoring of Salmonella serovar dissemination and resistance to antimicrobials is highly required

Tumor-Infiltrating Lymphocytes (TILs) and Risk of a Second Breast Event After a Ductal Carcinoma in situ

Women with a diagnosis of ductal carcinomain situ(DCIS) have a high risk of developing a second breast event (SBE). The immune system might play a role in trying to prevent a SBE. Patients diagnosed with DCIS were identified in the population-based cancer registry of Area Vasta Romagna from 1997 to 2010. Median follow-up is 8.5 years. Tumor-infiltrating lymphocytes (TILs) were evaluated both in index DCIS and in SBE. The main endpoint was to assess the association between TILs' levels in index DCIS and risk of a SBE. Out of 496 DCIS patients, 100 SBEs (20.2%) were identified: 55 ipsilateral (11.1%) and 43 contralateral (8.7%). The distribution of TILs was heterogeneous, but significantly associated with grade, necrosis, screen detection and type of surgery. Patients stratified according to TILs percentage (5%) did not show a statistically significant difference in the 5-year cumulative incidence of SBEs: 14.9% (95% CI 11.3-19.1) and 11.0% (95% CI, 6.9-16.2), respectively (p= 0.147). In the subgroup of patients who did not receive radiotherapy, TILs >5% were associated with a reduced risk of SBE (HR 0.34, 95% CI 0.14-0.82,p= 0.016). Although we did not find any significant association between TILs and SBE, further studies evaluating their role according to radiotherapy are warranted

Primeras edades U-Pb en circones detríticos del Grupo Neuquén en el extremo oriental de la Cuenca Neuquina (Paso Córdoba, Río Negro)

En esta contribución se dan a conocer las primeras edades U-Pb en circones detríticos de una muestra de los depósitos sinorogénicos del Cretácico Superior (Formación Anacleto) aflorantes en el extremo oriental de la cuenca Neuquina, en Paso Córdoba, Río Negro, Argentina. La edad máxima depositacional obtenida es de 78,6±1,7 Ma (Campaniano medio). La edad se calculó sobre la base de un grupo de circones jóvenes cretácicos (n=11), a partir del análisis de una muestra extraída de los depósitos de interduna húmeda, asignados a la Formación Anacleto del Grupo Neuquén

Plasminogen activation triggers transthyretin amyloidogenesis in vitro

Systemic amyloidosis is a usually fatal disease caused by extracellular accumulation of abnormal protein fibers, amyloid fibrils, derived by misfolding and aggregation of soluble globular plasma protein precursors. Both WT and genetic variants of the normal plasma protein transthyretin (TTR) form amyloid, but neither the misfolding leading to fibrillogenesis nor the anatomical localization of TTR amyloid deposition are understood. We have previously shown that, under physiological conditions, trypsin cleaves human TTR in a mechano-enzymatic mechanism that generates abundant amyloid fibrils in vitro. In sharp contrast, the widely used in vitro model of denaturation and aggregation of TTR by prolonged exposure to pH 4.0 yields almost no clearly defined amyloid fibrils. However, the exclusive duodenal location of trypsin means that this enzyme cannot contribute to systemic extracellular TTR amyloid deposition in vivo. Here, we therefore conducted a bioinformatics search for systemically active tryptic proteases with appropriate tissue distribution, which unexpectedly identified plasmin as the leading candidate. We confirmed that plasmin, just as trypsin, selectively cleaves human TTR between residues 48 and 49 under physiological conditions in vitro. Truncated and full-length protomers are then released from the native homotetramer and rapidly aggregate into abundant fibrils indistinguishable from ex vivo TTR amyloid. Our findings suggest that physiological fibrinolysis is likely to play a critical role in TTR amyloid formation in vivo. Identification of this surprising intersection between two hitherto unrelated pathways opens new avenues for elucidating the mechanisms of TTR amyloidosis, for seeking susceptibility risk factors, and for therapeutic innovation

First U-PB Detrital Zircon Ages of The Neuquén Group in the eastern sector of The Neuquén Basin (Paso Córdoba, Río Negro)

En esta contribución se dan a conocer las primeras edades U-Pb en circones detríticos de una muestra de los depósitos sinorogénicos del Cretácico Superior (Formación Anacleto) aflorantes en el extremo oriental de la cuenca Neuquina, en Paso Córdoba, Río Negro, Argentina. La edad máxima depositacional obtenida es de 78,6±1,7 Ma (Campaniano medio). La edad se calculó sobre la base de un grupo de circones jóvenes cretácicos (n=11), a partir del análisis de una muestra extraída de los depósitos de interduna húmeda, asignados a la Formación Anacleto del Grupo Neuquén.This work provides new U-Pb detrital zircon ages of the eastern synorogenic Upper Cretaceous deposits of the Neuquén Basin at Paso Córdoba, Río Negro, Argentina (Fig. 1). The Neuquén Basin is a large depocenter developed during the Late Triassic to Paleogene along the southwestern margin of Gondwana (30- 40°S). It originated by continental-scale rifting processes resulting in the break-up of the Pangea supercontinent. It records a thick Mesozoic sedimentary succession more than 7,000 m thick including marine and non-marine sedimentary rocks. Important geodynamic changes occurred during the latest Mesozoic with the accelerated westward movement of the South American plate following its separation from the African plate, and the continuation of subduction processes along its western margin, most notably the convergence between the Nazca-Farallón and the South American plates. This new compressive tectonic setting triggered the foreland basin deposition of the Neuquén Group. The non-marine Neuquén Group shows an important regional distribution and is characterized as the first foreland basin deposits linked with the early uplift of the Andean orogen at ca. 100 Ma. The Neuquén Group contains an important fossil record and is a reservoir rock in some depocenters of the basin. For this reason, it has been a well-studied unit in both the southern and central parts of the basin. Regionally, this stratigraphic unit is covered by Maastrichtian to Paleocene marine facies of the Malargüe Group. The Upper Cretaceous non-marine deposits of the Neuquén Basin have an important exposure in Paso Córdoba area (General Roca, Río Negro). According to Hugo and Leanza (2001), these deposits are included in the Bajo de la Carpa and Anacleto formations (Neuquén Group) and the overlying Allen Formation (Malargüe Group). These authors interpreted the contact between both groups as an erosional unconformity. Afterwards, Paz et al. (2014) and Díaz-Martínez et al. (2018) carried out detailed sedimentological and ichnological studies in the area, discussed the contact between both units and proposed a transitional passage between the Anacleto (lacustrine/fluvial facies) and Allen (aeolian facies) formations. The ages of the Anacleto and Allen formations are based on magnetostratigraphic and biostratigraphic data obtained in other localities to the west and north of the study area. Dingus et al. (2000) proposed an early-middle Campanian maximum depositional age for the Anacleto Formation (78.3 Ma) based on paleomagnetic studies in the Auca Mahuevo area (Neuquén). Furthermore, levels assigned to the overlying Allen Formation in the Lago Pellegrini area (Río Negro), contain an ostracod fauna from the upper Campanian-lower Maastrichtian interval (Ballent, 1980). In this contribution, we use a sedimentological and geochronological approach to discuss the paleoenvironment, provenance and age of the Anacleto Formation in the Paso Córdoba area. The facies analysis carried out in this work corroborates the proposal made by Paz et al. (2014) and by Díaz-Martínez et al. (2018), allowing the recognition of three facies associations: (I) lacustrine, (II) wet interdunes and (III) dunes and dry interdunes (III), indicating an increase in the aridity of the depositional system towards the top of the studied succession. In particular, the sample APC01- 20 dated by U-Pb in detrital zircons was collected from the bottom of wet interdunes facies association (II) given its textural features and its importance in terms of their stratigraphic position (Fig. 1d and 2d). According to the frequency histogram and relative probability plot of detrital zircon ages obtained from APC01-20 sample analysis, a multimodal pattern of ages can be distinguished. The sample is represented by five main populations; 75 – 126 Ma (Cretaceous, 32%), 150 – 200 Ma (Jurassic, 31%), 254 – 282 Ma (Permian, 10%), 300 – 349 Ma (Carboniferous, 14%) and 358 - 405 Ma (Devonian, 11%). The sample also contains two isolated ages that represent 2% of the total (478 Ma, Ordovician and 1,217 Ma, Mesoproterozoic). The main peak (32%) corresponds to latest Early-Late Cretaceous zircons with a youngest graphical peak (YPP) of 81.9 Ma (Campanian) (Fig. 2a). For the calculation of the maximum depositional age, different ways of measurement were considered (Dickinson and Gehrels, 2009). As a result of data analysis, weighted mean average of the youngest cluster of two or more grain ages that overlap at 1σ uncertainty, was the estimation that was better adjusted for the sample. The age calculation based on a sample of young Cretaceous zircons (n=11) pointed towards a maximum depositional age of 78.6 ± 1.7 Ma (middle Campanian) for the Anacleto Formation. The number of zircons used for the calculation of the maximum depositional age, together with the morphology of the measured crystals, suggest a coeval volcanic activity during the deposition of Anacleto Formation.Fil: Gómez, Ricardo Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; Argentina. Universidad Nacional de Río Negro; ArgentinaFil: Tunik, Maisa Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; Argentina. Universidad Nacional de Río Negro; ArgentinaFil: Casadio, Silvio Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; Argentina. Universidad Nacional de Río Negro; ArgentinaFil: Canale, Nerina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; Argentina. Universidad Nacional de Río Negro; ArgentinaFil: Greco, Gerson Alan. Universidad Nacional de Río Negro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; ArgentinaFil: Baiano, Mattia Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; Argentina. Provincia del Neuquén. Municipalidad de Villa El Chocón. Museo Paleontológico "Ernesto Bachmann"; ArgentinaFil: Pino, Diego Alejandro. Universidad Nacional de Río Negro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; ArgentinaFil: Báez, Alejandro David. Universidad Nacional de Río Negro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; ArgentinaFil: Pereira Da Silva, Sara Maria. Universidad Nacional de Río Negro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; Argentin

First U-PB Detrital Zircon Ages of The Neuquén Group in the eastern sector of The Neuquén Basin (Paso Córdoba, Río Negro)

En esta contribución se dan a conocer las primeras edades U-Pb en circones detríticos de una muestra de los depósitos sinorogénicos del Cretácico Superior (Formación Anacleto) aflorantes en el extremo oriental de la cuenca Neuquina, en Paso Córdoba, Río Negro, Argentina. La edad máxima depositacional obtenida es de 78,6±1,7 Ma (Campaniano medio). La edad se calculó sobre la base de un grupo de circones jóvenes cretácicos (n=11), a partir del análisis de una muestra extraída de los depósitos de interduna húmeda, asignados a la Formación Anacleto del Grupo Neuquén.This work provides new U-Pb detrital zircon ages of the eastern synorogenic Upper Cretaceous deposits of the Neuquén Basin at Paso Córdoba, Río Negro, Argentina (Fig. 1). The Neuquén Basin is a large depocenter developed during the Late Triassic to Paleogene along the southwestern margin of Gondwana (30- 40°S). It originated by continental-scale rifting processes resulting in the break-up of the Pangea supercontinent. It records a thick Mesozoic sedimentary succession more than 7,000 m thick including marine and non-marine sedimentary rocks. Important geodynamic changes occurred during the latest Mesozoic with the accelerated westward movement of the South American plate following its separation from the African plate, and the continuation of subduction processes along its western margin, most notably the convergence between the Nazca-Farallón and the South American plates. This new compressive tectonic setting triggered the foreland basin deposition of the Neuquén Group. The non-marine Neuquén Group shows an important regional distribution and is characterized as the first foreland basin deposits linked with the early uplift of the Andean orogen at ca. 100 Ma. The Neuquén Group contains an important fossil record and is a reservoir rock in some depocenters of the basin. For this reason, it has been a well-studied unit in both the southern and central parts of the basin. Regionally, this stratigraphic unit is covered by Maastrichtian to Paleocene marine facies of the Malargüe Group. The Upper Cretaceous non-marine deposits of the Neuquén Basin have an important exposure in Paso Córdoba area (General Roca, Río Negro). According to Hugo and Leanza (2001), these deposits are included in the Bajo de la Carpa and Anacleto formations (Neuquén Group) and the overlying Allen Formation (Malargüe Group). These authors interpreted the contact between both groups as an erosional unconformity. Afterwards, Paz et al. (2014) and Díaz-Martínez et al. (2018) carried out detailed sedimentological and ichnological studies in the area, discussed the contact between both units and proposed a transitional passage between the Anacleto (lacustrine/fluvial facies) and Allen (aeolian facies) formations. The ages of the Anacleto and Allen formations are based on magnetostratigraphic and biostratigraphic data obtained in other localities to the west and north of the study area. Dingus et al. (2000) proposed an early-middle Campanian maximum depositional age for the Anacleto Formation (78.3 Ma) based on paleomagnetic studies in the Auca Mahuevo area (Neuquén). Furthermore, levels assigned to the overlying Allen Formation in the Lago Pellegrini area (Río Negro), contain an ostracod fauna from the upper Campanian-lower Maastrichtian interval (Ballent, 1980). In this contribution, we use a sedimentological and geochronological approach to discuss the paleoenvironment, provenance and age of the Anacleto Formation in the Paso Córdoba area. The facies analysis carried out in this work corroborates the proposal made by Paz et al. (2014) and by Díaz-Martínez et al. (2018), allowing the recognition of three facies associations: (I) lacustrine, (II) wet interdunes and (III) dunes and dry interdunes (III), indicating an increase in the aridity of the depositional system towards the top of the studied succession. In particular, the sample APC01- 20 dated by U-Pb in detrital zircons was collected from the bottom of wet interdunes facies association (II) given its textural features and its importance in terms of their stratigraphic position (Fig. 1d and 2d). According to the frequency histogram and relative probability plot of detrital zircon ages obtained from APC01-20 sample analysis, a multimodal pattern of ages can be distinguished. The sample is represented by five main populations; 75 – 126 Ma (Cretaceous, 32%), 150 – 200 Ma (Jurassic, 31%), 254 – 282 Ma (Permian, 10%), 300 – 349 Ma (Carboniferous, 14%) and 358 - 405 Ma (Devonian, 11%). The sample also contains two isolated ages that represent 2% of the total (478 Ma, Ordovician and 1,217 Ma, Mesoproterozoic). The main peak (32%) corresponds to latest Early-Late Cretaceous zircons with a youngest graphical peak (YPP) of 81.9 Ma (Campanian) (Fig. 2a). For the calculation of the maximum depositional age, different ways of measurement were considered (Dickinson and Gehrels, 2009). As a result of data analysis, weighted mean average of the youngest cluster of two or more grain ages that overlap at 1σ uncertainty, was the estimation that was better adjusted for the sample. The age calculation based on a sample of young Cretaceous zircons (n=11) pointed towards a maximum depositional age of 78.6 ± 1.7 Ma (middle Campanian) for the Anacleto Formation. The number of zircons used for the calculation of the maximum depositional age, together with the morphology of the measured crystals, suggest a coeval volcanic activity during the deposition of Anacleto Formation.Fil: Gómez, Ricardo Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; Argentina. Universidad Nacional de Río Negro; ArgentinaFil: Tunik, Maisa Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; Argentina. Universidad Nacional de Río Negro; ArgentinaFil: Casadio, Silvio Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; Argentina. Universidad Nacional de Río Negro; ArgentinaFil: Canale, Nerina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; Argentina. Universidad Nacional de Río Negro; ArgentinaFil: Greco, Gerson Alan. Universidad Nacional de Río Negro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; ArgentinaFil: Baiano, Mattia Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; Argentina. Provincia del Neuquén. Municipalidad de Villa El Chocón. Museo Paleontológico "Ernesto Bachmann"; ArgentinaFil: Pino, Diego Alejandro. Universidad Nacional de Río Negro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; ArgentinaFil: Báez, Alejandro David. Universidad Nacional de Río Negro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; ArgentinaFil: Pereira Da Silva, Sara Maria. Universidad Nacional de Río Negro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigación en Paleobiología y Geología; Argentin

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011

Measurements of Higgs boson production and couplings in diboson final states with the ATLAS detector at the LHC

Measurements are presented of production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs, H →γ γ, H → Z Z∗ →4l and H →W W∗ →lνlν. The results are based on the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV, corresponding to an integrated luminosity of about 25 fb−1. Evidence for Higgs boson production through vector-boson fusion is reported. Results of combined fits probing Higgs boson couplings to fermions and bosons, as well as anomalous contributions to loop-induced production and decay modes, are presented. All measurements are consistent with expectations for the Standard Model Higgs boson

Measurement of the top quark-pair production cross section with ATLAS in pp collisions at \sqrt{s}=7\TeV

A measurement of the production cross-section for top quark pairs(\ttbar) in $pp$ collisions at \sqrt{s}=7 \TeV is presented using data recorded with the ATLAS detector at the Large Hadron Collider. Events are selected in two different topologies: single lepton (electron $e$ or muon $\mu$) with large missing transverse energy and at least four jets, and dilepton ($ee$, $\mu\mu$ or $e\mu$) with large missing transverse energy and at least two jets. In a data sample of 2.9 pb-1, 37 candidate events are observed in the single-lepton topology and 9 events in the dilepton topology. The corresponding expected backgrounds from non-\ttbar Standard Model processes are estimated using data-driven methods and determined to be $12.2 \pm 3.9$ events and $2.5 \pm 0.6$ events, respectively. The kinematic properties of the selected events are consistent with SM \ttbar production. The inclusive top quark pair production cross-section is measured to be \sigmattbar=145 \pm 31 ^{+42}_{-27} pb where the first uncertainty is statistical and the second systematic. The measurement agrees with perturbative QCD calculations.Comment: 30 pages plus author list (50 pages total), 9 figures, 11 tables, CERN-PH number and final journal adde