Lo sviluppo digitale: l'effetto della diffusione della banda larga nei comuni italiani e le determinanti degli investimenti NGN nelle province italiane

Il lavoro è dedicato allo studio dello sviluppo di un'economia digitale. Le opportunità offerte dallo sviluppo delle infrastrutture di comunicazione e dai servizi digitali contribuiscono alla coesione sociale e alla crescita economica del Paese. I primi due capitoli sono inerenti al fenomeno della diffusione della banda larga, il terzo ed il quarto capitolo riguardano gli investimenti nelle reti di nuova generazione

Determination of pesticides in the respirable fraction of airborne particulate matter by high-performance liquid chromatography–tandem mass spectrometry

Potential harmful effects of pesticides include risks to human health of workers involved in the wet spray application in cultivated areas. Inhalation exposure depends on several factors including pesticide concentrations in the respirable fraction of airborne particulate matter (PM4). To ensure a high level of protection, the use of tractors with cabins provides protection against dust, aerosols, and vapors. Since tractors not providing maximum protection are still in use, PM4 was sampled during spreading operations in agricultural fields inside and outside tractor cabins. Sample preparation technique based on accelerated solvent extraction and solid-phase extraction cleanup was optimized before analysis of nine pesticides in PM4. Meptyldinocap, deltamethrin, myclobutanil, fluopyram, methoxyfenozide, dimethomorph, fluopicolide, cyflufenamid, and metrafenone were simultaneously determined by high-performance liquid chromatography–electrospray ionization–tandem mass spectrometry (HPLC–ESI–MS–MS). The results demonstrated the efficacy of the tractor cabs used in the sampling sites. © 2017 Taylor & Francis

The brain network organization during sleep onset after deprivation

Objective: Aim of the present study is to investigate the alterations of brain networks derived from EEG analysis in pre- and post-sleep onset conditions after 40 h of sleep deprivation (SD) compared to sleep onset after normal sleep in 39 healthy subjects. Methods: Functional connectivity analysis was made on electroencelographic (EEG) cortical sources of current density and small world (SW) index was evaluated in the EEG frequency bands (delta, theta, alpha, sigma and beta). Results: Comparing pre- vs. post-sleep onset conditions after a night of SD a significant decrease of SW in delta and theta bands in post-sleep onset condition was found together with an increase of SW in sigma band. Comparing pre-sleep onset after sleep SD versus pre-sleep onset after a night of normal sleep a decreased of SW index in beta band in pre-sleep onset in SD compared to pre-sleep onset in normal sleep was evidenced. Conclusions: Brain functional network architecture is influenced by the SD in different ways. Brain networks topology during wake resting state needs to be further explored to reveal SD-related changes in order to prevent possible negative effects of SD on behaviour and brain function during wakefulness. Significance: The SW modulations as revealed by the current study could be used as an index of an altered balance between brain integration and segregation processes after SD

Influence of chemical and mineralogical soil properties on the adsorption of sulfamethoxazole and diclofenac in Mediterranean soils

Abstract Background The irrigation with treated wastewaters can be a way for the introduction of organic contaminants in soils. However, their adsorption onto soils can allow a control of their bioavailability and leaching. The adsorption is influenced by properties of contaminants (water solubility, chemical structure) and soils (organic matter content, pH, mineralogy). This study aimed to investigate the effect of mineralogical composition, organic matter content and others parameters of soils on the adsorption of sulfamethoxazole (SMX) and diclofenac (DCF), two contaminants of emerging concerns (CECs), in real cases (Altamura, Sibari and Noci soils). Results The isotherms data showed that the adsorption of the two CECs closely matched the Freundlich model, even if the DCF could also fit the linear one. The only exception was the adsorption of SMX on the soil of Sibari, for which Langmuir's model fitted better. In all cases, the Kd values were the highest for Altamura soil according mainly to its content of organic carbon. Positive correlations were found between Kd value of DCF and the soil organic carbon and Al oxyhydroxides content, suggesting their roles in its adsorption, while SMX showed only a slight positive correlation with the soil organic carbon content. Finally, between the two CECs studied, DCF was more adsorbed than SMX also because of the lower water solubility of the former. Conclusions The good interaction between DCF and soil organic carbon suggests the organic amendment of soils before the application of treated watewaters. The low adsorption of SMX onto soils suggests greater leaching of this compound which is, therefore, potentially more dangerous than DCF. For this reason, the application of a filtration system with appropriate adsorbent materials before the application of wastewater to soils should be expected. Graphical Abstrac

Validation of a modified QuEChERS method for the extraction of multiple classes of pharmaceuticals from soils

Abstract Background The quick, easy, cheap, effective, rugged, and safe (QuEChERS) method can be employed for multi-residue analyses instead of traditional extraction methods due to its advantages in terms of extraction time and required equipment. A modified version of the QuEChERS method has been developed for quantifying eight pharmaceuticals belonging to different classes in three real soils with different chemical properties. Firstly, the soils have been polluted with all contaminants and the recoveries were determined by liquid chromatography tandem–mass spectrometry. Due to similar recoveries from the three soils, the validation of the method has been carried out only on a soil by determining linearity, recovery, precision, limit of detection (LOD) and limit of quantification (LOQ) values. A matrix-matched calibration for the soil has been adopted in order to avoid the matrix effect and three levels of fortification (50, 100 and 500 µg L−1) were used. Results The recovery of all pharmaceuticals, with the exception of tetracycline, from any soil was between 72 and 113%. In the validation procedure, recoveries of fortified samples ranged from 80 to 99%, the relative standard deviations ranged between 1.2 and 11.8%, and the LOQ between 20 and 36.9 μg kg−1. Conclusion The results of the present study confirmed the validity of the modified QuEChERS method for the extraction of pharmaceuticals from soils in the range 50–500 μg kg−1. Graphical Abstrac

Naples Prognostic Score Predicts Tumor Regression Grade in Resectable Gastric Cancer Treated with Preoperative Chemotherapy

: Despite recent progresses, locally advanced gastric cancer remains a daunting challenge to embrace. Perioperative chemotherapy and D2-gastrectomy depict multimodal treatment of gastric cancer in Europe, shows better results than curative surgery alone in terms of downstaging, micrometastases elimination, and improved long-term survival. Unfortunately, preoperative chemotherapy is useless in about 50% of cases of non-responder patients, in which no effect is registered. Tumor regression grade (TRG) is directly related to chemotherapy effectiveness, but its understanding is achieved only after surgical operation; accordingly, preoperative chemotherapy is given indiscriminately. Conversely, Naples Prognostic Score (NPS), related to patient immune-nutritional status and easily obtained before taking any therapeutic decision, appeared an independent prognostic variable of TRG. NPS was calculated in 59 consecutive surgically treated gastric cancer patients after neoadjuvant FLOT4-based chemotherapy. 42.2% of positive responses were observed: all normal NPS and half mild/moderate NPS showed significant responses to chemotherapy with TRG 1-3; while only 20% of the worst NPS showed some related benefits. Evaluation of NPS in gastric cancer patients undergoing multimodal treatment may be useful both in selecting patients who will benefit from preoperative chemotherapy and for changing immune-nutritional conditions in order to improve patient's reaction against the tumor

Human lung adenocarcinoma cell cultures derived from malignant pleural effusions as model system to predict patients chemosensitivity

BACKGROUND: Lung cancer is the leading cause of cancer related deaths and Malignant Pleural Effusion (MPE) is a frequent complication. Current therapies suffer from lack of efficacy in a great percentage of cases, especially when cancer is diagnosed at a late stage. Moreover patients' responses vary and the outcome is unpredictable. Therefore, the identification of patients who will benefit most of chemotherapy treatment is important for accurate prognostication and better outcome. In this study, using malignant pleural effusions (MPE) from non-small cell lung cancer (NSCLC) patients, we established a collection of patient-derived Adenocarcinoma cultures which were characterized for their sensitivity to chemotherapeutic drugs used in the clinical practice. METHODS: Tumor cells present in MPEs of patients with NSCLC were isolated by density gradient centrifugation, placed in culture and genotyped by next generation sequencing. In a subset of cases patient derived xenografts (PDX) were obtained upon tumor cell inoculation in rag2/IL2 knock-out mice. Isolated primary cultures were characterized and tested for drug sensitivity by in vitro proliferation assays. Additivity, antagonism or synergy for combinatorial treatments were determined by analysis with the Calcusyn software. RESULTS: We have optimized isolation procedures and culture conditions to expand in vitro primary cultures from Malignant Pleural Effusions (MPEs) of patients affected by lung adenocarcinomas, the most frequent form of non small cell lung cancer. Using this approach we have been able to establish 16 primary cultures from MPEs. Cells were banked at low passages and were characterized for their mutational pattern by next generation sequencing for most common driver mutations in lung cancer. Moreover, amplified cultures were shown to engraft with high efficiency when injected in immunocompromised mice. Cancer cell sensitivity to drugs used in standard chemotherapy regimens was assessed either individually or in combination. Differential chemosensitivity and different mutation profiles were observed which suggests that this isolation method could provide a platform for predicting the efficacy of chemotherapy in the clinical setting. Most importantly for six patients it was possible to establish a correlation between drug response in vitro and response to therapy in the clinic. CONCLUSIONS: Results obtained using primary cultured cells from MPEs underscore the heterogeneity of NSCLC in advanced stage as indicated by drug response and mutation profile. Comparison of data obtained from in vitro assays with patients' responses to therapy leads to the conclusion that this strategy may provide a potentially useful approach for evaluating individual chemosensitivity profile and tailor the therapy accordingly. Furthermore, combining MPE-derived primary cultures with their genomic testing allows to identify patients eligible to trials with novel targeted agents

Combination of antibodies directed against different ErbB3 surface epitopes prevents the establishment of resistance to BRAF/MEK inhibitors in melanoma

Patients with metastatic melanoma bearing V600 mutations in BRAF oncogene clinically benefit from the treatment with BRAF inhibitors alone or in combination with MEK inhibitors. However, a limitation to such treatment is the occurrence of resistance. Tackling the adaptive changes helping cells survive from drug treatment may offer new therapeutic opportunities. Very recently the ErbB3 receptor has been shown to act as a central node promoting survival of BRAF mutated melanoma. In this paper we first demonstrate that ErbB3/AKT hyperphosphorylation occurs in BRAF mutated melanoma cell lines following exposure to BRAF and/or MEK inhibitors. This strongly correlates with increased transcriptional activation of its ligand neuregulin. Anti-ErbB3 antibodies impair the establishment of de novo cell resistance to BRAF inhibition in vitro. In order to more potently ablate ErbB3 activity we used a combination of two anti-ErbB3 antibodies directed against distinct epitopes of its extracellular domain. These two antibodies in combo with BRAF/MEK inhibitors potently inhibit in vitro cell growth and tumor regrowth after drug withdrawal in an in vivo xenograft model. Importantly, residual tumor masses from mice treated by the antibodies and BRAF/ERK inhibitors combo are characterized almost exclusively by large necrotic areas with limited residual areas of tumor growth. Taken together, our findings support the concept that triple therapy directed against BRAF/MEK/ErbB3 may be able to provide durable control of BRAF mutated metastatic melanoma