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The World Health Organization classification of myelodysplastic syndromes (MDS) is based on morphological evaluation of marrow dysplasia. We performed a systematic review of cytological and histological data from 1150 patients with peripheral blood cytopenia. We analyzed the frequency and discriminant power of single morphological abnormalities. A score to define minimal morphological criteria associated to the presence of marrow dysplasia was developed. This score showed high sensitivity/specificity (>90%), acceptable reproducibility and was independently validated. The severity of granulocytic and megakaryocytic dysplasia significantly affected survival. A close association was found between ring sideroblasts and SF3B1 mutations, and between severe granulocytic dysplasia and mutation of ASXL1 , RUNX1 , TP53 and SRSF2 genes. In myeloid neoplasms with fibrosis, multilineage dysplasia, hypolobulated/multinucleated megakaryocytes and increased CD34+ progenitors in the absence of JAK2 , MPL and CALR gene mutations were significantly associated with a myelodysplastic phenotype. In myeloid disorders with marrow hypoplasia, granulocytic and/or megakaryocytic dysplasia, increased CD34+ progenitors and chromosomal abnormalities are consistent with a diagnosis of MDS. The proposed morphological score may be useful to evaluate the presence of dysplasia in cases without a clearly objective myelodysplastic phenotype. The integration of cytological and histological parameters improves the identification of MDS cases among myeloid disorders with fibrosis and hypocellularity.

Neutron detection is nowadays mostly based on 3 He gas detectors, but its shortage and the continuous upgrades of the neutron facilities require new devices to perform experiments with maximum performances. This work presents a new detector based on the Gas Electron Multiplier (GEM) combined with several boron layers. This detector combines the features of GEM technology with the properties of boron as a neutron converter and the device is produced to sustain high neutron fluxes with high detection efficiency. The detector has been characterised at the ISIS Pulsed Neutron and Muon Source (UK). Based on the analysis of our results, the detector has shown a good response to thermal and epithermal neutrons reaching a detection efficiency of 16% at 1.8 Å (25 meV). The good detection efficiency (even increasable with the addition of further boron GEM foils) and the good time resolution, make the detector a unique device for the neutron techniques. In particular, its use can easily be envisaged in techniques involving neutron transmission measurements, that require high fluxes impinging on the detectors, with the added bonus of a 2D-resolved capability due to the padded anode.

Engineered silica nanoparticles (NPs) have attracted increasing interest in several applications, and particularly in the field of nanomedicine, thanks to the high biocompatibility of this material. For their optimal and controlled use, the understanding of the mechanisms elicited by their interaction with the biological target is a prerequisite, especially when dealing with cells particularly vulnerable to environmental stimuli like neurons. Here we have combined different electrophysiological approaches (both at the single cell and at the population level) with a genomic screening in order to analyze, in GT1-7 neuroendocrine cells, the impact of SiO NPs (50 ± 3 nm in diameter) on electrical activity and gene expression, providing a detailed analysis of the impact of a nanoparticle on neuronal excitability. We find that 20 µg mL NPs induce depolarization of the membrane potential, with a modulation of the firing of action potentials. Recordings of electrical activity with multielectrode arrays provide further evidence that the NPs evoke a temporary increase in firing frequency, without affecting the functional behavior on a time scale of hours. Finally, NPs incubation up to 24 hours does not induce any change in gene expression.

A new position-sensitive thermal neutron detector based on boron-coated converters has been developed as an alternative to today’s standard 3 He -based technology for application to thermal neutron scattering. The key elements of the development are the boron-coated GEM foils (Sauli in Nucl Instrum Methods Phys Res Sect A Accel Spectrom Detect Assoc Equip 386:531, 1997) that are used as a multi-layer neutron converter via the 10 B ( n , α ) 7 Li reaction together with an efficient collection of the produced secondary electrons. This paper reports the test performed on a 3 layers converter prototype coupled to a GEMPix detector (Murtas in Radiat Meas 138:106421, 2020), carried out in order to study the possibility to produce a large-scale multi-layer neutron detector capable to reach high detection efficiency with high spatial resolution and able to sustain the high neutron flux expected in the new neutron spallation source under development like the ESS.

Engineered silica nanoparticles (NPs) have attracted increasing interest in several applications, and particularly in the field of nanomedicine, thanks to the high biocompatibility of this material. For their optimal and controlled use, the understanding of the mechanisms elicited by their interaction with the biological target is a prerequisite, especially when dealing with cells particularly vulnerable to environmental stimuli like neurons. Here we have combined different electrophysiological approaches (both at the single cell and at the population level) with a genomic screening in order to analyze, in GT1-7 neuroendocrine cells, the impact of SiO 2 NPs (50 ± 3 nm in diameter) on electrical activity and gene expression, providing a detailed analysis of the impact of a nanoparticle on neuronal excitability. We find that 20 µg mL −1 NPs induce depolarization of the membrane potential, with a modulation of the firing of action potentials. Recordings of electrical activity with multielectrode arrays provide further evidence that the NPs evoke a temporary increase in firing frequency, without affecting the functional behavior on a time scale of hours. Finally, NPs incubation up to 24 hours does not induce any change in gene expression.

Lately the problem of 3 He replacement for neutron detection stimulated an intense activity research on alternative technologies based on alternative neutron converters. This paper presents briefly the results obtained with new GEM detectors optimized for fast and thermal neutrons. For thermal neutrons, we realized a side-on GEM detector based on a series of boron-coated alumina sheets placed perpendicularly to the incident neutron beam direction. This prototype has been tested at n@BTF photo-production neutron facilty in order to test its effectiveness under a very high flux gamma background. For fast neutrons, we developed new GEM detectors (called nGEM) for the CNESM diagnostic system of the SPIDER NBI prototype for ITER (RFX-Consortium, Italy) and as beam monitor for fast neutrons lines at spallation sources. The nGEM is a Triple GEM gaseous detector equipped with a polyethylene layer used to convert fast neutrons into recoil protons through the elastic scattering process. This paper describes the results obtained by testing a medium size (30 × 25 cm 2 active area) nGEM detector at the ISIS spallation source on the VESUVIO beam line.

Fast neutron measurements were performed on the VESUVIO beam-line at the ISIS spallation source using a new telescope proton recoil spectrometer. Neutrons interact on a plastic target. Proton production is mainly due to elastic scattering on hydrogen nuclei and secondly due to interaction with carbon nuclei. Recoil protons are measured by a proton spectrometer, which uses in coincidence a 2.54 cm thick YAP scintillator and a 500$\\mu$m thick silicon detector, measuring the full proton recoil energy and the partial deposited energy in transmission, respectively. Recoil proton spectroscopy measurements (up to $E_{p} = 60$MeV) have been interpreted by using Monte Carlo simulations of the beam-line. This instrument is of particular interest for the characterization of the ChipIr beam-line at ISIS, which was designed to feature an atmospheric-like neutron spectrum for the irradiation of micro-electronics.

Research into valid alternatives to $^{3}$He detectors is fundamental to the affordability of new neutron spallation sources like the European Spallation Source (ESS). In the case of ESS it is also essential to develop high-rate detectors that can fully exploit the increase of neutron flux relative to present neutron sources. One of the technologies fulfilling these requirements is the gas electron multiplier (GEM), since it can combine a high rate capability (MHz$/$mm$^{2}$), a coverage area up to 1 m$^{2}$ and a space resolution better than 0.5 mm. Its use as a neutron detector requires conversion of neutrons into charged particles. This paper describes the realization and characterization of a thermal neutron GEM-based beam monitor equipped with a cathode containing $^{10}$B for neutron conversion. This device is constituted by a triple GEM detector whose cathode is made of an aluminum sheet covered by a 1 $\\mu $m thick $^{\\hbox{nat}}$B$_{4}$C layer. The method used to realize a long-lasting $^{{\\mathrm {nat}}}$B$_{4}$C layer is described and the properties of such a layer have been determined. The detector performances (measured on the ISIS-VESUVIO beam line) in terms of beam profile reconstruction, imaging, and measurement of the thermal neutron beam energy spectrum are compatible with those obtained by standard beam monitors.

Background Depression is a frequently observed and disabling condition in primary care, mainly treated by Primary Care Physicians with antidepressant drugs. Psychological interventions are recommended as first-line treatment by the most authoritative international guidelines but few evidences are available on their efficacy and effectiveness for mild depression. Methods/Design This multi-center randomized controlled trial was conducted in 9 Italian centres with the aim to compare the efficacy of Inter-Personal Counseling, a brief structured psychological intervention, to that of Selective Serotonin Reuptake Inhibitors. Patients with depressive symptoms referred by Primary Care Physicians to psychiatric consultation-liaison services were eligible for the study if they met the DSM-IV criteria for major depression, had a score ≥13 on the 21-item Hamilton Depression Rating Scale, and were at their first or second depressive episode. The primary outcome was remission of depressive symptoms at 2-months, defined as a HDRS score ≤ 7. Secondary outcome measures were improvement in global functioning and recurrence of depressive symptoms at 12-months. Patients who did not respond to Inter-Personal Counseling or Selective Serotonin Reuptake Inhibitors at 2-months received augmentation with the other treatment. Discussion This trial addresses some of the shortcomings of existing trials targeting major depression in primary care by evaluating the comparative efficacy of a brief psychological intervention that could be easily disseminated, by including a sample of patients with mild/moderate depression and by using different outcome measures. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12608000479303

The RES-NOVA project is an experimental initiative aimed at detecting neutrinos from the next galactic supernova using PbWO\\(_4\\) cryogenic detectors, operated at low temperatures in a low-background environment. By utilizing archaeological lead (Pb) as the target material, RES-NOVA leverages its high radiopurity, large nuclear mass, and the natural abundance of \\(^207\\)Pb, making it well-suited for exploring both spin-independent and spin-dependent Dark Matter (DM) interactions via nuclear scattering. This work presents a background model developed for the RES-NOVA technology demonstrator and evaluates its implications for Dark Matter detection. Detailed calculations of nuclear matrix elements, combined with the unique properties of archaeological Pb, demonstrate RES-NOVA's potential as a complementary tool to existing direct detection experiments for studying Dark Matter interactions. The experiment will conduct DM searches over a broad mass range spanning 4 orders of magnitude, from sub-GeV/\\(c^2\\) to TeV/\\(c^2\\). In the most optimistic scenario, RES-NOVA is expected to probe DM-nucleon cross-sections down to 1\\( 10^-43\\) cm\\(^2\\) and 2\\( 10^-46\\) cm\\(^2\\) for candidates with masses of 2 GeV/\\(c^2\\) and 20 GeV/\\(c^2\\), respectively.