A novel TOF-PET MRI detector for diagnosis and follow up of the prostate cancer

Prostate cancer is the most common disease in men and the second leading cause of death from cancer. Generic large imaging instruments used in cancer diagnosis have sensitivity, spatial resolution, and contrast inadequate for the task of imaging details of a small organ such as the prostate. In addition, multimodality imaging can play a significant role merging anatomical and functional details coming from simultaneous PET and MRI. Indeed, multi-parametric PET/MRI was demonstrated to improve diagnosis, but it suffers from too many false positives. In order to address the above limits of the current techniques, we have proposed, built and tested, thanks to the TOPEM project funded by Italian National Institute of Nuclear Phisics a prototype of an endorectal PET-TOF/MRI probe. In the applied magnification PET geometry, performance is dominated by a high-resolution detector placed closer to the source. The expected spatial resolution in the selected geometry is about 1.5 mm FWHM and efficiency a factor of 2 with respect to what obtained with the conventional PET scanner. In our experimental studies, we have obtained timing resolution of ~ 320 ps FWHM and at the same time Depth of Interaction (DOI) resolution of under 1 mm. Tests also showed that mutual adverse PET-MR effects are minimal. In addition, the matching endorectal RF coil was designed, built and tested. In the next planned studies, we expect that benefiting from the further progress in scintillator crystal surface treatment, in SiPM technology and associated electronics would allow us to significantly improve TOF resolutio

Effectiveness of dolutegravir-based regimens as either first-line or switch antiretroviral therapy: data from the Icona cohort

Introduction: Concerns about dolutegravir (DTG) tolerability in the real-life setting have recently arisen. We aimed to estimate the risk of treatment discontinuation and virological failure of DTG-based regimens from a large cohort of HIV-infected individuals. Methods: We performed a multicentre, observational study including all antiretroviral therapy (ART)-naïve and virologically suppressed treatment-experienced (TE) patients from the Icona (Italian Cohort Naïve Antiretrovirals) cohort who started, for the first time, a DTG-based regimen from January 2015 to December 2017. We estimated the cumulative risk of DTG discontinuation regardless of the reason and for toxicity, and of virological failure using Kaplan–Meier curves. We used Cox regression model to investigate predictors of DTG discontinuation. Results: About 1679 individuals (932 ART-naïve, 747 TE) were included. The one- and two-year probabilities (95% CI) of DTG discontinuation were 6.7% (4.9 to 8.4) and 11.5% (8.7 to 14.3) for ART-naïve and 6.6% (4.6 to 8.6) and 7.6% (5.4 to 9.8) for TE subjects. In both ART-naïve and TE patients, discontinuations of DTG were mainly driven by toxicity with an estimated risk (95% CI) of 4.0% (2.6 to 5.4) and 2.5% (1.3 to 3.6) by one year and 5.6% (3.8 to 7.5) and 4.0% (2.4 to 5.6) by two years respectively. Neuropsychiatric events were the main reason for stopping DTG in both ART-naïve (2.1%) and TE (1.7%) patients. In ART-naïve, a concomitant AIDS diagnosis predicted the risk of discontinuing DTG for any reason (adjusted relative hazard (aRH) = 3.38, p = 0.001), whereas starting DTG in combination with abacavir (ABC) was associated with a higher risk of discontinuing because of toxicity (aRH = 3.30, p = 0.009). TE patients starting a DTG-based dual therapy compared to a triple therapy had a lower risk of discontinuation for any reason (adjusted hazard ratio (aHR) = 2.50, p = 0.037 for ABC-based triple-therapies, aHR = 3.56, p = 0.012 for tenofovir-based) and for toxicity (aHR = 5.26, p = 0.030 for ABC-based, aHR = 6.60, p = 0.024 for tenofovir-based). The one- and two-year probabilities (95% CI) of virological failure were 1.2% (0.3 to 2.0) and 4.6% (2.7 to 6.5) in the ART naïve group and 2.2% (1.0 to 3.3) and 2.9% (1.5 to 4.3) in the TE group. Conclusions: In this large cohort, DTG showed excellent efficacy and optimal tolerability both as first-line and switching ART. The low risk of treatment-limiting toxicities in ART-naïve as well as in treated individuals reassures on the use of DTG in everyday clinical practice

Impact of social determinants on antiretroviral therapy access and outcomes entering the era of universal treatment for people living with HIV in Italy

Background: Social determinants are known to be a driving force of health inequalities, even in high income countries. Aim of our study was to determine if these factors can limit antiretroviral therapy (ART) access, outcome and retention in care of people living with HIV (PLHIV) in Italy. Methods: All ART naïve HIV+ patients (pts) of Italian nationality enrolled in the ICONA Cohort from 2002 to 2016 were included. The association of socio-demographic characteristics (age, sex, risk factor for HIV infection, educational level, occupational status and residency area) with time to: ART initiation (from the first positive anti-HIV test), ART regimen discontinuation, and first HIV-RNA < 50 cp/mL, were evaluated by Cox regression analysis, Kaplan Meier method and log-rank test. Results: A total of 8023 HIV+ pts (82% males, median age at first pos anti-HIV test 36 years, IQR: 29-44) were included: 6214 (77.5%) started ART during the study period. Women, people who inject drugs (PWID) and residents in Southern Italy presented the lowest levels of education and the highest rate of unemployment compared to other groups. Females, pts aged > 50 yrs., unemployed vs employed, and people with lower educational levels presented the lowest CD4 count at ART initiation compared to other groups. The overall median time to ART initiation was 0.6 years (yrs) (IQR 0.1-3.7), with a significant decrease over time [2002-2006 = 3.3 yrs. (0.2-9.4); 2007-2011 = 1.0 yrs. (0.1-3.9); 2012-2016 = 0.2 yrs. (0.1-2.1), p < 0.001]. By multivariate analysis, females (p < 0.01) and PWID (p < 0.001), presented a longer time to ART initiation, while older people (p < 0.001), people with higher educational levels (p < 0.001), unemployed (p = 0.02) and students (p < 0.001) were more likely to initiate ART. Moreover, PWID, unemployed vs stable employed, and pts. with lower educational levels showed a lower 1-year probability of achieving HIV-RNA suppression, while females, older patients, men who have sex with men (MSM), unemployed had higher 1-year risk of first-line ART discontinuation. Conclusions: Despite median time to ART start decreased from 2002 to 2016, socio-demographic factors still contribute to disparities in ART initiation, outcome and durability

Infection caused by Sporothrix schenckii: an autochthonous case in Bari, Southern Italy

An autochthonous case of lymphocutaneous sporotrichosis caused by Sporothrix schenckii is reported. The patient developed skin lesions localized along the lymphatics that appeared after he suffered an injury while collecting wicker canes in marshy water. The fungus was identified as Sporothrix schenckii by MALDI-TOF and sequencing. Phylogenetic analysis was also performed. Low MIC values were detected for all tested echinocandins and azoles except for fluconazole. The patient was treated with itraconazole without significant improvement. A regression of lesions was observed after 3 months of therapy with voriconazole. Few cases of sporotrichosis have been reported in Europe. However, several cases of sporotrichosis have been described in Italy. The incidence of sporotrichosis in Italy may be underestimated and microbiologists, and clinicians must be aware of this fungal infection

A progress report on the development of the CsI-RICH detector for the ALICE experiment at LHC

The particle identification in ALICE (A Large Ion Collider Experiment) at LHC will be achieved by two complementary systems based on time of flight measurement, at low $p_t$, and on the Ring Imaging Cherenkov (RICH) technique, at $p_t$ ranging from 2 to 5 GeV/$c$, respectively. The High Momentum PID (HMPID) system will cover $\sim$5\% of the phase space, the single arm detector array beeing composed by seven 1.3$\times$1.3 m$^2$ CsI-RICH modules placed at 4.7 m from the interaction point where a density of about 50 particles/m$^2$ is expected.\\ A 1 m$^2$ prototype, 2/3 of HMPID module size, has been successfully tested at the CERN/PS beam where 18 photoelectrons per event have been obtained with 3 GeV/c pions and 10 mm liquid $\mathrm{C}_6\mathrm{F}_{14}$ radiator. Mechanical problems related to the liquid radiator vessel construction have been solved and the prototype, fully equipped, will be tested at the CERN/SPS to investigate the PID capability in high particle density events.\\ In this report, after an introductory discussion on the requirements for PID in ALICE, the HMPID prototype is described and the main results of beam tests on large area CsI photocathodes, operated in RICH detectors, are given

Antimicrobial resistance gene shuffling and a three-element mobilisation system in the monophasic Salmonella typhimurium strain ST1030

In this study we describe the genetic elements and the antimicrobial resistance units (RUs) harboured by the Salmonella Typhimurium monophasic variant 1,4,[5],12:i:- strain ST1030. Of the three identified RUs two were chromosomal, RU1 (IS26-blaTEM-1-IS26-strAB-sul2- IS26) and RU2 (IS26-tetR(B)-tetA(B)-ΔIS26), and one, RU3 (a sul3-associated class 1 integron with cassette array dfrA12-orfF-aadA2-cmlA1-aadA1), was embedded in a Tn21-derived element harboured by the conjugative I1 plasmid pST1030-1A. IS26 elements mediated the antimicrobial resistance gene (ARG) shuffling and this gave rise to pST1030-1A derivatives with different sets of ARGs. ST1030 also harboured two ColE1-like plasmids of which one, pST1030-2A, was mobilisable and the target of an intracellular translocation of the Tn21-derived element; the second (pST1030-3) was an orphan mob-associated oriT plasmid co-transferred with pST1030-1A and pST1030-2A. pST1030-2A and pST1030-3 also carried a parA gene and a type III restriction modification system, respectively. Overall analysis of our data reinforces the role played by IS26, Tn21-derived elements and non-conjugative plasmids in the spread of ARGs and supplies the first evidence, at least in Salmonella, for the identification of a natural isolate harbouring a three-element mobilisation system in the same cell

Chert sources and territorial behaviour after the Neolithization process: An exploratory analysis from Grotta Battifratta (Rieti, Central Italy)

This paper aims at investigating lithic raw material acquisition strategies and human mobility in the Sabina region (Central Italy) during the Neolithic period through the Non-destructive Multiparametric Protocol for Chert Investigation (NM-PCI) applied to the lithic assemblage of Grotta Battifratta (Sabina region, Rieti). Despite its importance as a unique natural bridge in the middle of the Italian peninsula, Sabina has long been archaeologically underestimated. Moreover, although rich in siliceous rock sources, a solid knowledge of chert availability and distribution is lacking. By applying a pilot analysis on raw material provenance, this work aims at shedding light on i.) chert-bearing deposits in the region and ii.) human territorial behaviour. Furthermore, the preliminary characterization data of the Sabina chert is presented here as part of the first project of construction of a geological reference collection, currently lacking for the area. Geological samples and the lithic assemblage of Grotta Battifratta have been characterized by applying petrographical, geochemical (pXRF) and colorimetric analysis (CIELab). Multivariate statistics is employed to explore chert variability and to assess the geographic origin of the raw material exploited at the archaeological site. The preliminary results suggest a strong reliance on local sources together with a short but significant introduction of exogenous raw material, whose origin is still under investigation. This research presents a preliminary analysis of chert in the Sabina region and provides a novel strategy to current research in lithic raw material provenance in the Central Italy

Local epidemics gone viral: Evolution and diffusion of the Italian HIV-1 recombinant form CRF60_BC

The molecular epidemiology of HIV-1 in Italy is becoming increasingly complex, mainly due to the spread of non-B subtypes and the emergence of new recombinant forms. We previously characterized the outbreak of the first Italian circulating recombinant form (CRF60_BC), occurring among young MSM living in Apulia between the years 2009 and 2011. Here we show a 5-year follow-up surveillance to trace the evolution of CRF60_BC and to investigate its further spread in Italy. We collected additional sequences and clinical data from patients harboring CRF60_BC, enrolled at the Infectious Diseases Clinic of the University of Bari. In addition to the 24 previously identified sequences, we retrieved 27 CRF60_BC sequences from patients residing in Apulia, whose epidemiological and clinical features did not differ from those of the initial outbreak, i.e., the Italian origin, young age at HIV diagnosis (median: 24 years; range: 18-37), MSM risk factor (23/25, 92%) and recent infection (from 2008 to 2017). Sequence analysis revealed a growing overall nucleotide diversity, with few nucleotide changes that were fixed over time. Twenty-seven additional sequences were detected across Italy, spanning multiple distant regions. Using a BLAST search, we also identified a CRF60_BC sequence isolated in United Kingdom in 2013. Three patients harbored a unique second generation recombinant form in which CRF60_BC was one of the parental strains. Our data show that CRF60_BC gained epidemic importance, spreading among young MSM in multiple Italian regions and increasing its population size in few years, as the number of sequences identified so far has triplicated since our first report. The observed further divergence of CRF60_BC is likely due to evolutionary bottlenecks and host adaptation during transmission chains. Of note, we detected three second-generation recombinants, further supporting a widespread circulation of CRF60_BC and the increasing complexity of the HIV-1 epidemic in Italy

Laser Focusing System for High Brightness Polarized Electron Source for SPLEEM

For construction of a high brightness polarized electron source for SPLEEM (Spin Polarized Low Energy Electronic Microscope), a new transmission type photocathode has been developed at Nagoya Univ. In our scheme, a laser light is injected from backside of the photocathode and an electron beam is emitted forward from the surface. A high numerical aperture lens with a short focal length can focus the laser lights into a small spot of photocathode. A laser spot with a diameter of 2.2μm could be achieved by our laser system, and it contributed to realize the high beam brightness of 10^5A·cm^{-2}·sr^{-1} or more for a total current of 5μA.journal articl

High-Dose, Extended-Interval Colistin Administration in Critically Ill Patients: Is This the Right Dosing Strategy? A Preliminary Study

In critically ill patients with otherwise untreatable nosocomial infection due to gram-negative bacteria susceptible only to colistin, a high-dose, extended-interval colistin dosing regimen is, according to the pharmacokinetic/pharmacodynamic behavior of the drug, associated with low renal toxicity and high efficacy