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The study of clustering states in neutron-rich nuclei is an important subject of research in the field of nuclear physics, steadily growing in interest in the international scientific community. In this context, break-up reactions play an important role for the characterization of exotic states in radioactive light nuclei, like neutron halos around stable cores, α-clustering structures or exotic clusters. The CLIR (Clusters in Light Ion Reactions) experiment was performed at INFN - Laboratori Nazionali del Sud (LNS), aiming at the investigation of such states in light radioactive nuclei, by producing a radioactive beam at the FRIBs facility. Reaction products were detected by the CHIMERA multidetector, coupled with four telescopes of the FARCOS array. Calibrations of the tagging system and of the FARCOS telescopes have been performed, for which accurate procedures have been carried out. In this paper, results on the analysis will be presented. Moreover, a brief review on the new fragment separator FRAISE, currently under construction at LNS, will be given.

The development of new detectors based on Silicon Carbide (SiC) is currently a topic of interest within the scientific community. The significant features of SiC make it highly promising for detecting charged particles, neutrons, and \\(\\)/X radiation. In this framework, within the SAMOTHRACE (Sicilian Micro and Nano Technology Research and Innovation Center) ecosystem, an array of new-generation SiC detectors is under development, specifically designed for nuclear and medical investigations using radioactive ion beams. This paper describes the results obtained in the characterization of SiC prototypes regarding energy and timing measurements. A new method, based on coincidence data analysis, is employed to evaluate the timing performances of SiC detectors. The obtained results have been compared with tests performed using a micro-channel plate as a start detector reference for timing measurements.

Hepatocellular carcinoma (HCC) is a primary liver tumor developing in the wake of chronic liver disease. Chronic liver disease and inflammation leads to a fibrotic environment actively supporting and driving hepatocarcinogenesis. Insight into hepatocarcinogenesis in terms of the interplay between the tumor stroma micro-environment and tumor cells is thus of considerable importance. Three-dimensional (3D) cell culture models are proposed as the missing link between current in vitro 2D cell culture models and in vivo animal models. Our aim was to design a novel 3D biomimetic HCC model with accompanying fibrotic stromal compartment and vasculature. Physiologically relevant hydrogels such as collagen and fibrinogen were incorporated to mimicking the bio-physical properties of the tumor ECM. In our model LX2 and HepG2 cells embedded in a hydrogel matrix were seeded onto the inverted insert membrane of a Transwell™ system. HUVEC cells were then seeded onto the opposite side of the membrane. Three formulations consisting of ECM-hydrogels embedded with cells were prepared and the bio-physical properties determined by rheology. Cell viability was determined by the AlamarBlue® assay over 21-days. The effect of the chemotherapeutic drug doxorubicin was evaluated in both a 2D co-culture and our 3D model for a period of 72h. We show that this model is viable for 25-days and gives rise to metastatic tumor nodules after 17 days in culture. Rheology results show that bio-physical properties of a fibrotic, cirrhotic and HCC liver can be successfully mimicked. Overall, results indicate that this 3D model is more representative of the in vivo situation compared to traditional 2D cultures. Our 3D tumor model showed a decreased response to chemotherapeutics, mimicking drug resistance typically seen in HCC patients. This model could in future provide a valuable new platform to study multifocal HCC or to identify mechanisms that contribute to early stages of metastasis. A protocol for a novel 3D biomimetic HCC model with accompanying fibrotic stromal compartment and vasculature, to study endocrine and paracrine signaling in liver cancer. The model uses physiological relevant hydrogels in ratios mimicking the bio-physical properties of the stromal extracellular matrix, which is an active mediator of cellular interactions, tumor growth and metastasis.

Endovascular thrombectomy (EVT) is the standard of care for large vessel occlusion stroke. Use of Computed Tomographic Perfusion (CTP) to select EVT candidates is variable. The frequency of treatment and outcome in patients with unfavourable CTP patterns is unknown. A retrospective analysis of CTP utilisation prior to EVT was conducted. All CTP data were analysed centrally and a Target Mismatch was defined as an infarct core ≤70 ml, penumbral volume ≥15ml, and a total hypoperfused volume:core volume ratio >1.8. The primary outcome was good functional outcome at 90 days, defined as a modified Rankin Scale (mRS) score 0–2. follow-up infarct volume, core expansion and penumbral salvage volumes were secondary outcomes. Of 572 anterior circulation EVT patients, CTP source image data required to generate objective maps were available in 170, and a Target Mismatch was present in 151 (89%). The rate of 90-day good functional outcome was similar between Target Mismatch (53%) and Large Core Non-Mismatch groups (46%, p = 0.629). Median follow-up infarct volume in the Large Core Non-Mismatch group (104ml [IQR 25ml-189ml]) was larger than that in the Target Mismatch patients (16ml [8ml-47ml], p<0.001). Despite a lack of formal CTP selection criteria, the majority of patients treated at our centres had a Target Mismatch. Patients without Target Mismatch had larger follow-up infarct volumes, but the functional recovery rate was similar to that in Target Mismatch patients. Infarct volumes should be included as objective assessment criteria in the evaluation of the efficacy of EVT in non-Target Mismatch patients.

Levofloxacin (LVF) is an antibacterial drug approved for the treatment of ocular infections. However, due to the low ocular bioavailability, high doses are needed, causing bacterial resistance. Polymeric nanospheres (NPs) loading antibiotic drugs represent the most promising approach to eradicate ocular infections and to treat pathogen resistance. In this study, we have developed chitosan NPs based on sulfobutyl-ether-β-cyclodextrin (CH/SBE-β-CD NPs) for ocular delivery of LVF. CH/SBE-β-CD NPs loading LVF were characterized in terms of encapsulation parameters, morphology, and sizes, in comparison to NPs produced without the macrocycle. Nuclear magnetic resonance and UV–vis spectroscopy studies demonstrated that SBE-β-CD is able to complex LVF and to influence encapsulation parameters of NPs, producing high encapsulation efficiency and LVF loading. The NPs were homogenous in size, with a hydrodynamic radius between 80 and 170 nm and positive zeta potential (ζ) values. This surface property could promote the interaction of NPs with the negatively charged ocular tissue, increasing their residence time and, consequently, LVF efficacy. In vitro, antibacterial activity against Gram-positive and Gram-negative bacteria showed a double higher activity of CH/SBE-β-CD NPs loading LVF compared to the free drug, suggesting that chitosan NPs based on SBE-β-CD could be a useful system for the treatment of ocular infections.

Background: Dementia following stroke is common but its determinants are still incompletely understood. Methods: In the Sydney Stroke Study, we performed detailed neuropsychological and medical-psychiatric assessments on 169 patients aged 50–85 years, 3–6 months after a stroke, and 103 controls with a majority of both groups undergoing MRI brain scans. Stroke subjects were diagnosed as having vascular mild cognitive impairment (VaMCI) or vascular dementia (VaD) or no cognitive impairment by consensus. Demographic, functional, cerebrovascular risk factors and neuroimaging parameters were examined as determinants of dementia using planned logistic regression. Results: 21.3% of subjects were diagnosed with VaD, with one case in those aged 50–59 years, 24% in those aged 60–69 years and 23% in those 70–79 years. There was no difference by sex. The prevalence of VaMCI was 36.7%. VaD subjects had lower premorbid intellectual functioning and had 0.9 years less education than controls. The VaD and VaMCI groups did not differ from the no cognitive impairment group on any specific cerebrovascular risk factor, however overall those with impairment had a greater number of risk factors. They did not differ consistently on depression severity, homocysteine levels and neuroimaging parameters (atrophy, infarct volume and number of infarcts) except for an excess of white matter lesions on MRI and greater number of infarcts in the VaD and VaMCI groups. On a series of logistic regression analyses, stroke volume and premorbid function were significant determinants of cognitive impairment in stroke patients. Conclusion: Post-stroke dementia and MCI are common, especially in older individuals. Cerebrovascular risk factors are not independent risk factors for VaD, but stroke volume is a significant determinant of dementia. Premorbid functioning is a determinant of post- stroke impairment.

The present study provides insight into specific zooplankton oxygen and carbon demands (per unit biomass) and community zooplankton respiration and carbon requirements in the Ross Sea (Antarctica). In the literature, there is a lack of data in this area. The role of mesozooplankton in carbon remineralisation in coastal and pelagic environments was evaluated. The zooplankton composition, abundance and biomass were analysed. In the marine carbon cycle, zooplankton from the epipelagic realm has a key role. Estimation of the electron transport system activity represents a specific and highly sensitive method to evaluate the zooplankton carbon requirements from the sinking flux as an indication of the respiratory activity. We focus here on 26 sampling stations in the western sector of the Ross Sea, in which the 0–250-m layer was investigated during the austral summer of 2014. The oxygen consumption from the electron transport system analysis was converted into carbon demand. Differences in carbon requirements were observed, and their relationships to zooplanktonic composition and abundance were investigated, along with their relationships to seawater temperature, food availability, non-living specimens and pteropod faecal pellet abundance. A positive correlation between carbon demand and temperature was highlighted. The change in copepod community composition was relevant in terms of species and relative size ranges. The zooplankton biomass ranged from 41.25 to 171.46 mg m −3 among the stations, which is in agreement with the late summer trophic condition, with higher values for the more coastal stations. Positive correlation between zooplankton biomass and community metabolism per day was revealed. With its recycling of the particulate organic material that originates in the epipelagic layer, the zooplankton compartment participates in the decrease in the input of material, mainly in the two coastal areas investigated, with respect the more pelagic zone.

Mesozooplankton plays a role in particulate organic carbon (POC) remineralisation from the pelagic sinking POC flux down the water column. The vertical distribution (to 1000 m depth), diel variability (during a 24 h cycle) and seasonal differences of the mesozooplankton carbon requirement (μg C g–1 d–1), estimated by measuring the activity of the electron transport system, were investigated at a fixed station in the southern Adriatic Sea during November 2006 and April 2007. To estimate the quantitative role of zooplankton in the carbon loss that occurs during organic particle sinking, the zooplankton carbon requirement was compared with organic carbon vertical fluxes measured using a sediment trap. Zooplankton abundance, biomass and community composition were investigated along with the diel vertical distribution of euphausiid migrating groups and the relative importance of crustaceans and gelatinous taxa to the potential community carbon requirement. Day/night zooplankton carbon requirement differences in the upper 100 m were shown in both sampling periods. They were not at all correlated to the vertical distribution pattern of euphausiids but were attributable to the amount of non-living specimens and/or the ratio between gelatinous and crustacean taxa. The mean metabolic requirement in the sampled layers of the water column was lower in November than in April, ranging from 0.02 to 9.10% and from 0.07 to 31.86%, respectively, of the measured carbon losses. In the epi- and mesopelagic zones, the total percent contributions of mesozooplankton respiration to organic carbon losses were 0.18 and 18.45%, respectively, in November and 1.41 and 87.27%, respectively, in April. The higher remineralisation percentages detected in April compared to November could be linked to seasonal differences that involve higher primary production, zooplankton biomass, vertical amount of sinking POC flux and more intense heterotrophic metabolism, which take place mainly in the meso pelagic layer in each period.

Background Results of several randomized clinical trials (RCTs) testing the combination of an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) plus an anti-angiogenic drug in advanced EGFR-mutated non–small cell lung cancer were reported. Methods We first report a systematic review and meta-analysis of all RCTs to estimate effectiveness and toxicity of this new therapeutic approach compared with first-generation EGFR-TKI monotherapy. Subsequently, we present a network meta-analysis comparing the combination of an EGFR-TKI plus an anti-angiogenic drug with 2 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 progression-free survival (PFS) was statistically significantly larger in patients treated with an EGFR-TKI plus an anti-angiogenic drug compared with EGFR-TKI monotherapy: the pooled PFS–hazard ratio (HR) was 0.59 (95% confidence interval [CI] = 0.51 to 0.69). The pooled median-PFS was 17.8 months (95% CI = 16.5 to 19.3 months) for the combination vs 11.7 months (95% CI = 11.1 to 12.7 months) for EGFR-TKI as monotherapy. No statistically significant differences between the 2 treatment arms were observed in overall survival or objective response rate. The rate of grade equal or higher than 3 adverse events 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 network meta-analysis. All 3 experimental treatments were associated with a statistically significant improvement in PFS compared with first-generation EGFR-TKIs. When compared to each other, none of the 3 experimental treatments were statistically significantly associated with larger PFS or lower rate of grade 3 or higher adverse events. Conclusion Patients with EGFR-mutated non small-cell lung cancer 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 toxicities.

Quantitative sampling of zooplankton communities from ice-covered waters presents many technical and logistic difficulties. Currently available techniques enable only vertical tows through relatively small ice holes, and the filtered volumes are generally low. For these reasons, we developed and tested Micro-Net Environmental Sampling System (MicroNESS), an innovative small-sized opening–closing multinet device carried by a ROV for horizontal and oblique sampling of the under-ice zooplankton community. MicroNESS design ensures a filtration efficiency close to 90 % due to the relevant filtration open area ratio (~4) and exhibited only limited effects of clogging and avoidance for optimal speed of 0.35 ms −1 and towing duration not longer than 14 min with mean filtered volumes in the order of 11 m 3 . MicroNESS was successfully tested in Terra Nova Bay (Antarctica). A total of 96 tows were carried out to sample the zooplankton in the waters below the 2.6-m-thick pack ice, far from the ice hole, at selected depths (3.5, 4.5, 5.0, 6.0, 7.0, 10.0 and 20.0 m). Overall, more than 70,000 specimens were identified, mostly copepod taxa, which showed a size range from the small Stephos longipes nauplius stage I (0.11 mm) to the large adult females of Calanoides acutus (4.8 mm). The comparison among the ice-associated copepod communities collected by MicroNESS and those of three traditional sampling techniques showed that MicroNESS can provide useful insights about changes in composition, biomass and particle size structure of this key plankton component, especially on a short timescale during ice melting.