Foodborne Salmonellosis in Italy: Characterization of Salmonella enterica Serovar Typhimurium and Monophasic Variant 4,[5],12:i- Isolated from Salami and Human Patients.

Salmonella enterica serovar Typhimurium (STm) and its monophasic variant 4,[5],12:i:- (VMSTm) have been responsible for an increased number of foodborne infections in humans in Europe in recent years. The aim of this study was to investigate the origin of three foodborne salmonellosis outbreaks that occurred in Pavia Province (Lombardy region, northern Italy) in 2010. Phenotypic and genetic characteristics of the STm and VMSTm isolates from patients and from food that were recovered in the framework of the three outbreaks were evaluated through serotyping, phage typing, antimicrobial susceptibility testing, pulsed-field gel electrophoresis (PFGE), and multiple-locus variable-number tandem repeat analysis (MLVA). Salami from three artisan producers, which had all purchased meat from the same slaughterhouse, was the food source of infection in outbreak I. STm isolates were recovered from salami and patients with symptoms of gastroenteritis. These isolates had the same PFGE type and the same rare MLVA profile (3-18-9-NA-211). The same molecular profiles were found in an STm isolate from a salami, which likely was the source of another family outbreak (II). A VMSTm strain with common phenotypic and molecular profiles was isolated from three hospitalized patients and identified as the cause of another putative outbreak (III). During the following 3 years (2011 through 2013), 360 salami produced in Pavia Province were monitored for the presence of S. enterica . In 2011, no STm and VMSTm isolates were recovered from 159 salami tested. During 2012 and 2013, 13.9% of 201 tested salami harbored S. enterica , and half of the isolates were VMSTm, mainly in salami from those artisan producers involved in the previous outbreaks. These isolates were genetically variable, especially in terms of MLVA profiles. The data collected suggest that from 2012, VMSTm has replaced STm in the environments of the salami producers monitored in this study, and these data confirm the dominance of this emergent serovar along the pork supply chain

An accurate low-redshift measurement of the cosmic neutral hydrogen density

Using a spectral stacking technique, we measure the neutral hydrogen (HI) properties of a sample of galaxies at $z < 0.11$ across 35 pointings of the Westerbork Synthesis Radio Telescope (WSRT). The radio data contains 1,895 galaxies with redshifts and positions known from the Sloan Digital Sky Survey (SDSS). We carefully quantified the effects of sample bias, aperture used to extract spectra, sidelobes and weighting technique and use our data to provide a new estimate for the cosmic HI mass density. We find a cosmic HI mass density of $\Omega_{\rm HI} = (4.02 \pm 0.26)\times 10^{-4} h_{70}^{-1}$ at $\langle z\rangle = 0.066$, consistent with measurements from blind HI surveys and other HI stacking experiments at low redshifts. The combination of the small interferometer beam size and the large survey volume makes our result highly robust against systematic effects due to confusion at small scales and cosmic variance at large scales. Splitting into three sub-samples with $\langle z\rangle$ = 0.038, 0.067 and 0.093 shows no significant evolution of the HI gas content at low redshift.Comment: 17 pages, 24 figure

Organ Stiffness in the Work-Up of Myelofibrosis and Philadelphia-Negative Chronic Myeloproliferative Neoplasms

To define the role of spleen stiffness (SS) and liver stiffness (LS) in myelofibrosis and other Philadelphia (Ph)-negative myeloproliferative neoplasms (MPNs), we studied, by ultrasonography (US) and elastography (ES), 70 consecutive patients with myelofibrosis (MF) (no.43), essential thrombocythemia (ET) (no.10), and polycythemia vera (PV) (no.17). Overall, the median SS was not different between patients with MF and PV (p = 0.9); however, both MF and PV groups had significantly higher SS than the ET group (p = 0.011 and p = 0.035, respectively) and healthy controls (p &lt; 0.0001 and p = 0.002, respectively). In patients with MF, SS values above 40 kPa were significantly associated with worse progression-free survival (PFS) (p = 0.012; HR = 3.2). SS also correlated with the extension of bone marrow fibrosis (BMF) (p &lt; 0.0001). SS was higher in advanced fibrotic stages MF-2, MF-3 (W.H.O. criteria) than in pre-fibrotic/early fibrotic stages (MF-0, MF-1) (p &lt; 0.0001) and PFS was significantly different in the two cohorts, with values of 63% and 85%, respectively (p = 0.038; HR = 2.61). LS significantly differed between the patient cohort with MF and healthy controls (p = 0.001), but not between the patient cohorts with ET and PV and healthy controls (p = 0.999 and p = 0.101, respectively). We can conclude that organ stiffness adds valuable information to the clinical work-up of MPNs and could be employed to define patients at a higher risk of progression

EGFR-TKI plus anti-angiogenic drugs in EGFR-mutated NSCLC: a meta-analysis of randomized clinical trials

Abstract Background Results of several RCTs testing the combination of an EGFR-TKI plus an anti-angiogenic drug in advanced EGFR-mutated NSCLC were reported. Methods We first report a systematic-review and meta-analysis of all RCTs, to estimate effectiveness and toxicity of such new therapeutic approach as compared with first-generation EGFR-TKIs monotherapy. Subsequently, we present a network meta-analysis (NMA) comparing the combination of an EGFR-TKI plus an anti-angiogenic drug with other two new treatment-options: combination of an EGFR-TKI plus chemotherapy or new EGFR-TKIs of second or third generation as monotherapy. Results Five RCTs were included in the first meta-analysis. The PFS was statistically significantly larger in patients treated with an EGFR-TKI plus an anti-angiogenic drug as compared with EGFR-TKI monotherapy: the pooled PFS-HR was 0.59 (95% CI = 0.51 to 0.69). The pooled median-PFS was 17.8 months (95% CI = 16.5 to 19.3) for the combination versus 11.7 months (95% CI = 11.1 to 12.7) for EGFR-TKI as monotherapy. No statistically significant differences between the two treatment-arms were observed in terms of both OS and ORR. The rate of grade equal or higher than 3 AEs was statistically significantly higher in patients treated with EGFR-TKI plus an anti-angiogenic drug: the pooled-Relative Risk was 1.72 (95% CI = 1.43 to 2.06). Ten RCTs were included in the NMA. All the three experimental treatments were associated with a statistically significant improvement of PFS as compared with first-generation EGFR-TKIs. When compared to each other, none of the three experimental treatments was statistically significantly associated with larger PFS or lower rate of grade ≥3AEs. Conclusion Patients with EGFR-mutated NSCLC derived clinically meaningful larger PFS-benefit from the addition of an anti-angiogenic drug to a first-generation EGFR-TKI, at the cost of an increase of toxicitie

PAK6 phosphorylates 14-3-3γ to regulate steady state phosphorylation of LRRK2

Mutations in Leucine-rich repeat kinase 2 (LRRK2) are associated with Parkinson's disease (PD) and, as such, LRRK2 is considered a promising therapeutic target for age-related neurodegeneration. Although the cellular functions of LRRK2 in health and disease are incompletely understood, robust evidence indicates that PD-associated mutations alter LRRK2 kinase and GTPase activities with consequent deregulation of the downstream signaling pathways. We have previously demonstrated that one LRRK2 binding partner is P21 (RAC1) Activated Kinase 6 (PAK6). Here, we interrogate the PAK6 interactome and find that PAK6 binds a subset of 14-3-3 proteins in a kinase dependent manner. Furthermore, PAK6 efficiently phosphorylates 14-3-3γ at Ser59 and this phosphorylation serves as a switch to dissociate the chaperone from client proteins including LRRK2, a well-established 14-3-3 binding partner. We found that 14-3-3γ phosphorylated by PAK6 is no longer competent to bind LRRK2 at phospho-Ser935, causing LRRK2 dephosphorylation. To address whether these interactions are relevant in a neuronal context, we demonstrate that a constitutively active form of PAK6 rescues the G2019S LRRK2-associated neurite shortening through phosphorylation of 14-3-3γ. Our results identify PAK6 as the kinase for 14-3-3γ and reveal a novel regulatory mechanism of 14-3-3/LRRK2 complex in the brain

Molecular and atomic gas in dust lane early-type galaxies - I : Low star-formation efficiencies in minor merger remnants

In this work we present IRAM-30m telescope observations of a sample of bulge-dominated galaxies with large dust lanes, which have had a recent minor merger. We find these galaxies are very gas rich, with H2 masses between 4x10^8 and 2x10^10 Msun. We use these molecular gas masses, combined with atomic gas masses from an accompanying paper, to calculate gas-to-dust and gas-to-stellar mass ratios. The gas-to-dust ratios of our sample objects vary widely (between ~50 and 750), suggesting many objects have low gas-phase metallicities, and thus that the gas has been accreted through a recent merger with a lower mass companion. We calculate the implied minor companion masses and gas fractions, finding a median predicted stellar mass ratio of ~40:1. The minor companion likely had masses between ~10^7 - 10^10 Msun. The implied merger mass ratios are consistent with the expectation for low redshift gas-rich mergers from simulations. We then go on to present evidence that (no matter which star-formation rate indicator is used) our sample objects have very low star-formation efficiencies (star-formation rate per unit gas mass), lower even than the early-type galaxies from ATLAS3D which already show a suppression. This suggests that minor mergers can actually suppress star-formation activity. We discuss mechanisms that could cause such a suppression, include dynamical effects induced by the minor merger.Peer reviewe

The commissioning of the CUORE experiment: the mini-tower run

CUORE is a ton-scale experiment approaching the data taking phase in Gran Sasso National Laboratory. Its primary goal is to search for the neutrinoless double-beta decay in 130Te using 988 crystals of tellurim dioxide. The crystals are operated as bolometers at about 10 mK taking advantage of one of the largest dilution cryostat ever built. Concluded in March 2016, the cryostat commissioning consisted in a sequence of cool down runs each one integrating new parts of the apparatus. The last run was performed with the fully configured cryostat and the thermal load at 4 K reached the impressive mass of about 14 tons. During that run the base temperature of 6.3 mK was reached and maintained for more than 70 days. An array of 8 crystals, called mini-tower, was used to check bolometers operation, readout electronics and DAQ. Results will be presented in terms of cooling power, electronic noise, energy resolution and preliminary background measurements

Results from the Cuore Experiment

The Cryogenic Underground Observatory for Rare Events (CUORE) is the first bolometric experiment searching for neutrinoless double beta decay that has been able to reach the 1-ton scale. The detector consists of an array of 988 TeO2 crystals arranged in a cylindrical compact structure of 19 towers, each of them made of 52 crystals. The construction of the experiment was completed in August 2016 and the data taking started in spring 2017 after a period of commissioning and tests. In this work we present the neutrinoless double beta decay results of CUORE from examining a total TeO2 exposure of 86.3kg yr, characterized by an effective energy resolution of 7.7 keV FWHM and a background in the region of interest of 0.014 counts/ (keV kg yr). In this physics run, CUORE placed a lower limit on the decay half- life of neutrinoless double beta decay of 130Te > 1.3.1025 yr (90% C. L.). Moreover, an analysis of the background of the experiment is presented as well as the measurement of the 130Te 2vo3p decay with a resulting half- life of T2 2. [7.9 :- 0.1 (stat.) :- 0.2 (syst.)] x 10(20) yr which is the most precise measurement of the half- life and compatible with previous results