Progress in Developing Hybrid RPCs: GEM-like Detectors with Resistive Electrodes

We have recently developed an innovative detector of photons and charged particles: a GEM-like gaseous amplification structure with resistive electrodes instead of commonly used metallic ones. This novel detector combines the best property of GEMs- the capability to operate in a cascaded mode and in poorly quenched gases - and of RPC: the protection against sparks. In this paper will shortly review our latest achievements in this direction, however the main focus will be given on a new advanced design that allows to build large area detectors manufactured by a screen printing technology. The proposed detector, depending on the applications, can operate either in a GEM mode (electron multiplications through holes only) or as a hybrid RPC with simultaneous amplifications in the drift region and in the holes. The possible applications of this new detector will be discussed

Effects of intravenous furosemide plus small-volume hypertonic saline solutions on markers of heart failure

Aims: We sought to compare the effects of furosemide + hypertonic saline solution (HSS) treatment in patients with acute decompensated heart failure in comparison with furosemide alone and the response in a compensated state after an acute saline load with regard to serum levels of heart failure biomarkers. Methods and results: We enrolled 141 patients with acute decompensated heart failure with reduced ejection fraction admitted to our Internal Medicine ward from March 2017 to November 2019. A total of 73 patients were randomized to treatment with i.v. high-dose furosemide plus HSS, whereas 68 patients were randomized to i.v. high-dose furosemide alone. Patients treated with furosemide plus HSS compared with controls treated with furosemide alone showed a comparable degree of reduction in the serum levels of interleukin (IL)-6, soluble suppression of tumorigenicity 2 (sST2), and N-terminal pro-brain natriuretic peptide (NT-proBNP) in the ‘between-group’ analysis. Nevertheless, patients treated with high-dose furosemide + HSS showed significantly higher absolute delta values of IL-6 (2.3 ± 1.2 vs. 1.7 ± 0.9, P < 0.0005, and 2.0 ± 0.8 vs. 1.85 ± 1.1, P = 0.034), sST2 (41.2 ± 8.6 vs. 27.9 ± 7.6, P < 0.0005, and 37.1 ± 6.6 vs. 28.4 ± 6.7, P < 0.0005), high-sensitivity troponin T (0.03 ± 0.02 vs. 0.02 ± 0.01, P = 0.001, and 0.03 ± 0.02 vs. 0.02 ± 0.01, P = 0.009), NT-proBNP (7237 ± 7931 vs. 3244 ± 4159, P < 0.005, and 5381 ± 4829 vs. 4466 ± 4332, P = 0.004), and galectin-3 (15.7 ± 3.2 ng/mL vs. 11.68 ± 1.9 ng/mL, P < 0.0005, and 16.7 ± 3.9 ng/mL vs. 11.8 ± 2.4 ng/mL, P < 0.0005) than patients treated with furosemide alone. After acute saline load, patients treated with i.v. furosemide + HSS in comparison with subjects treated with furosemide alone showed a significantly lower increase in the serum concentrations of IL-6 (−0.26 ± 0.42 pg/mL vs. −1.43 ± 0.86 pg/mL, P < 0.0005), high-sensitivity troponin T (0 vs. −0.02 ± 0.02 ng/mL, P < 0.0005), sST2 (−8.5 ± 5.9 ng/mL vs. −14.6 ± 6.2 ng/mL, P < 0.0005), galectin-3 (−2.1 ± 1.5 ng/mL vs. −7.1 ± 3.6 ng/mL, P < 0.0005), and NT-proBNP (77 ± 1373 vs. −1706 ± 2259 pg/mL, P < 0.0005). Conclusions: Our findings concerning a comparable degree of reduction in the serum levels of three cardinal biomarkers indicate that a reduction in serum heart failure markers is not linked to the higher degree of congestion relief with a more rapid achievement of a clinical compensation state. This issue may have possible benefits on clinical practice concerning its therapeutic effects over and beyond the simple amelioration of clinical congestion signs and symptoms. Nevertheless, our findings of higher delta values after treatment with i.v. furosemide plus HSS indicate a possible higher efficacy by means of modulation of the stretching and fibrosis mechanisms

Reactive hyperemia index (RHI) and cognitive performance indexes are associated with histologic markers of liver disease in subjects with non-alcoholic fatty liver disease (NAFLD): a case control study.

BACKGROUND: No study evaluated vascular health markers in subjects with non-alcoholic fatty liver disease (NAFLD) through a combined analysis of reactive hyperemia peripheral arterial tonometry (RH-PAT) and arterial stiffness indexes. AIM OF THE STUDY: We aimed to assess whether NAFLD and its histological severity are associated with impairment of arterial stiffness and RH-PAT indexes in a mixed cohort of patients with biopsy-proven NAFLD. MATERIALS AND METHODS: The Kleiner classification was used to grade NAFLD grade. Pulse wave velocity (PWV) and augmentation index (Aix) were used as markers of arterial stiffness, whereas endothelial function was assessed using reactive hyperemia index (RHI). The mini-mental state examination (MMSE) was administered to test cognitive performance. RESULTS: 80 consecutive patients with biopsy-proven NAFLD and 83 controls without fatty liver disease. NAFLD subjects showed significantly lower mean RHI, higher mean arterial stiffness indexes and lower mean MMSE score. Multivariable analysis after correction for BMI, dyslipidaemia, hypertension, sex, diabetes, age and cardiovascular disease showed that BMI, diastolic blood pressure and RHI are significantly associated to NAFLD. Simple linear regression analysis showed among non-alcoholic steatohepatitis (NASH) subjects a significant negative relationship between ballooning grade and MMSE and a significant positive association between Kleiner steatosis grade and augmentation index. CONCLUSIONS: Future research will be addressed to evaluate the relationship between inflammatory markers and arterial stiffness and endothelial function indexes in NAFLD subjects. These study will evaluate association between cardiovascular event incidence and arterial stiffness, endothelial and cognitive markers, and they will address the beneficial effects of cardiovascular drugs such as statins and ACE inhibitors on these surrogate markers in NAFLD subjects

Natural bovine coronavirus infection in a calf persistently infected with bovine viral diarrhea virus: Viral shedding, immunological features and s gene variations

The evolution of a bovine coronavirus (BCoV) natural infection in a calf persistently infected with bovine viral diarrhea virus (BVDV) was described. The infected calf developed intermittent nasal discharge, diarrhea and hyperthermia. The total number of leukocytes/mL and the absolute differential number of neutrophils and lymphocytes resulted within the normal range, but monocytes increased at T28 (time 28 post‐infection). Flow‐cytometry analysis evidenced that the CD8+ subpopulation increased at T7 and between T28 and T35. BCoV shedding in nasal discharges and feces was detected up to three weeks post infection and high antibody titers persisted up to T56. The RNA BCoV load increased until T14, contrary to what was observed in a previous study where the fecal excretion of BCoV was significantly lower in the co‐infected (BCoV/BVDV) calves than in the calves infected with BCoV only. We can suppose that BVDV may have modulated the BCoV infection exacerbating the long viral excretion, as well as favoring the onset of mutations in the genome of BCoV detected in fecal samples at T21. An extensive study was performed to verify if the selective pressure in the S gene could be a natural mode of variation of BCoV, providing data for the identification of new epidemic strains, genotypes or recombinant betacoronaviruses

Hydroxy-propil-β-cyclodextrin inclusion complexes of two biphenylnicotinamide derivatives: Formulation and anti-proliferative activity evaluation in pancreatic cancer cell models

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies, with poor outcomes largely due to its unique microenvironment, which is responsible for the low response to drugs and drug-resistance phenomena. This clinical need led us to explore new therapeutic approaches for systemic PDAC treatment by the utilization of two newly synthesized biphenylnicotinamide derivatives, PTA73 and PTA34, with remarkable antitumor activity in an in vitro PDAC model. Given their poor water solubility, inclusion complexes of PTA34 and PTA73 in Hydroxy-Propil-β-Cyclodextrin (HP-β-CD) were prepared in solution and at the solid state. Complexation studies demonstrated that HP-β-CD is able to form stable host–guest inclusion complexes with PTA34 and PTA73, characterized by a 1:1 apparent formation constant of 503.9 M−1 and 369.2 M−1, respectively (also demonstrated by the Job plot), and by an increase in aqueous solubility of about 150 times (from 1.95 µg/mL to 292.5 µg/mL) and 106 times (from 7.16 µg/mL to 762.5 µg/mL), in the presence of 45% w/v of HP-β-CD, respectively. In vitro studies confirmed the high antitumor activity of the complexed PTA34 and PTA73 towards PDAC cells, the strong G2/M phase arrest followed by induction of apoptosis, and thus their eligibility for PDAC therapy

Usability of VGI for validation of land cover maps

Volunteered Geographic Information (VGI) represents a growing source of potentially valuable data for many applications, including land cover map validation. It is still an emerging field and many different approaches can be used to take value from VGI, but also many pros and cons are related to its use. Therefore, since it is timely to get an overview of the subject, the aim of this article is to review the use of VGI as reference data for land cover map validation. The main platforms and types of VGI that are used and that are potentially useful are analysed. Since quality is a fundamental issue in map validation, the quality procedures used by the platforms that collect VGI to increase and control data quality are reviewed and a framework for addressing VGI quality assessment is proposed. A review of cases where VGI was used as an additional data source to assist in map validation is made, as well as cases where only VGI was used, indicating the procedures used to assess VGI quality and fitness for use. A discussion and some conclusions are drawn on best practices, future potential and the challenges of the use of VGI for land cover map validation

Development of innovative micropattern gaseous detectors with resistive electrodes and first results of their applications

The paper summarizes our latest progress in the development of newly introduced micro pattern gaseous detectors with resistive electrodes. These resistive electrodes protect the detector and the front-end electronics in case of occasional discharges and thus make the detectors very robust and reliable in operation. As an example, we describe in greater detail a new recently developed GEM-like detector, fully spark-protected with electrodes made of resistive kapton. We discovered that all resistive layers used in these studies (including kapton), that are coated with photosensitive layers, such as CsI, can be used as efficient photo cathodes for detectors operating in a pulse counting mode. We describe the first applications of such detectors combined with CsI or SbCs photo cathodes for the detection of UV photons at room and cryogenic temperatures.Comment: Presented at the 11 Vienna Conference on Instrumentation, February, 200

The sub-TeV transient Gamma-Ray sky: challenges and opportunities

The detection of gravitational waves and neutrinos from astrophysical sources with gamma-ray counterparts officially started the era of Multi-Messenger Astronomy. Their transient and extreme nature implies that monitoring the VHE sky is fundamental to investigate the non-electromagnetic signals. However, the limited effective area of space-borne instruments prevents observations above a few hundred GeV, while the small field of view and low duty cycle of IACTs make them unsuited for extensive monitoring activities and prompt response to transients. Extensive Air Shower arrays (EAS) can provide a large field of view, a wide effective area and a very high duty cycle. Their main difficulty is the distinction between gamma-ray and cosmic-ray initiated air showers, especially below the TeV range. Here we present some case studies stressing the importance that a new EAS array in the Southern Hemisphere will be able to survey the sky from below 100 GeV up to several TeV. In the energy domain between 100 and 400 GeV we expect the strongest electromagnetic signatures of the acceleration of ultra-relativistic particles in sources like SNRs, blazar jets and gamma-ray bursts, as recently proved by IACT observations. This spectral window is also crucial to understand the Universe opacity to high energy radiation, thus providing constraints on the cosmological parameters. We will discuss the implications of VHE radiation on the mechanisms at work and we will focus on the advantages resulting from the ability to monitor the energy window lying between the domain of space-borne detectors and ground-based facilities

Anisotropy and chemical composition of ultra-high energy cosmic rays using arrival directions measured by the Pierre Auger Observatory

The Pierre Auger Collaboration has reported evidence for anisotropy in the distribution of arrival directions of the cosmic rays with energies $E>E_{th}=5.5\times 10^{19}$ eV. These show a correlation with the distribution of nearby extragalactic objects, including an apparent excess around the direction of Centaurus A. If the particles responsible for these excesses at $E>E_{th}$ are heavy nuclei with charge $Z$, the proton component of the sources should lead to excesses in the same regions at energies $E/Z$. We here report the lack of anisotropies in these directions at energies above $E_{th}/Z$ (for illustrative values of $Z=6,\ 13,\ 26$). If the anisotropies above $E_{th}$ are due to nuclei with charge $Z$, and under reasonable assumptions about the acceleration process, these observations imply stringent constraints on the allowed proton fraction at the lower energies

Anisotropy studies around the galactic centre at EeV energies with the Auger Observatory

Data from the Pierre Auger Observatory are analyzed to search for anisotropies near the direction of the Galactic Centre at EeV energies. The exposure of the surface array in this part of the sky is already significantly larger than that of the fore-runner experiments. Our results do not support previous findings of localized excesses in the AGASA and SUGAR data. We set an upper bound on a point-like flux of cosmic rays arriving from the Galactic Centre which excludes several scenarios predicting sources of EeV neutrons from Sagittarius $A$. Also the events detected simultaneously by the surface and fluorescence detectors (the `hybrid' data set), which have better pointing accuracy but are less numerous than those of the surface array alone, do not show any significant localized excess from this direction.Comment: Matches published versio