Giovani lavoratori e contratto di apprendistato. Evidenza italiana.

Il presente lavoro analizza la dinamica del fenomeno occupazione in Italia limitatamente alle fasce più giovani della popolazione (15 – 29 anni) e ad una sola tipologia di rapporto di lavoro, il contratto di apprendistato. Alla stregua delle esperienze positive degli altri Paesi europei, il contratto di apprendistato è considerato dai governi italiani del XXI secolo una forma ottimale di ingresso nel mondo del lavoro principalmente per i più giovani non solo perché completa la formazione con il praticantato, ma anche perché costituisce una modalità di acquisizione di competenze ed esperienze lavorative da spendere nella professione. Il lavoro si delinea come un tentativo di fotografare un fenomeno ben circoscritto utilizzando il dato di fonte ISTAT riveniente dalla Rilevazione Continua delle Forze di Lavoro, per il periodo I trim. 2014 – II trim. 2018. Nonostante le note criticità del dato utilizzato, i risultati ottenuti sono soddisfacenti. Dall’analisi è emerso come il contratto di apprendistato venga sottoutilizzato in Italia per una serie di limitazioni che non solo sono propriamente ricollegabili alle caratteristiche del settore produttivo italiano, ma anche all’impianto della norma di riferimento. I risultati dell’analisi evidenziano caratteristiche di genere importanti sia per quel che riguarda l’inquadramento del lavoratore, sia per quel che riguarda il titolo di studio posseduto. Evidenze ricollegabili anche alle azioni del governo messe in atto su più fronti e dirette al mercato del lavoro emergono dall’analisi in modo evidente

Common and distinct lateralised patterns of neural coupling during focused attention, open monitoring and loving kindness meditation

Meditation has been integrated into different therapeutic interventions. To inform the evidence-based selection of specific meditation types it is crucial to understand the neural processes associated with different meditation practices. Here we explore commonalities and differences in electroencephalographic oscillatory spatial synchronisation patterns across three important meditation types. Highly experienced meditators engaged in focused attention, open monitoring, and loving kindness meditation. Improving on previous research, our approach avoids comparisons between groups that limited previous findings, while ensuring that the meditation states are reliably established. Employing a novel measure of neural coupling – the imaginary part of EEG coherence – the study revealed that all meditation conditions displayed a common connectivity pattern that is characterised by increased connectivity of (a) broadly distributed delta networks, (b) left-hemispheric theta networks with a local integrating posterior focus, and (c) right-hemispheric alpha networks, with a local integrating parieto-occipital focus. Furthermore, each meditation state also expressed specific synchronisation patterns differentially recruiting left- or right-lateralised beta networks. These observations provide evidence that in addition to global patterns, frequency-specific inter-hemispheric asymmetry is one major feature of meditation, and that mental processes specific to each meditation type are also supported by lateralised networks from fast-frequency bands

Attentional and cognitive monitoring brain networks in long-term meditators depend on meditation states and expertise.

Meditation practice is suggested to engage training of cognitive control systems in the brain. To evaluate the functional involvement of attentional and cognitive monitoring processes during meditation, the present study analysed the electroencephalographic synchronization of fronto-parietal (FP) and medial-frontal (MF) brain networks in highly experienced meditators during different meditation states (focused attention, open monitoring and loving kindness meditation). The aim was to assess whether and how the connectivity patterns of FP and MF networks are modulated by meditation style and expertise. Compared to novice meditators, (1) highly experienced meditators exhibited a strong theta synchronization of both FP and MF networks in left parietal regions in all mediation styles, and (2) only the connectivity of lateralized beta MF networks differentiated meditation styles. The connectivity of intra-hemispheric theta FP networks depended non-linearly on meditation expertise, with opposite expertise-dependent patterns found in the left and the right hemisphere. In contrast, inter-hemispheric FP connectivity in faster frequency bands (fast alpha and beta) increased linearly as a function of expertise. The results confirm that executive control systems play a major role in maintaining states of meditation. The distinctive lateralized involvement of FP and MF networks appears to represent a major functional mechanism that supports both generic and style-specific meditation states. The observed expertise-dependent effects suggest that functional plasticity within executive control networks may underpin the emergence of unique meditation states in expert meditators

Glycan and protein analysis of glycoengineered bacterial E. coli vaccines by MALDI-in-source decay FT-ICR mass spectrometry

Bacterial glycoconjugate vaccines have a major role in preventing microbial infections. Immunogenic bacterial glycans, suchas O-antigen polysaccharides, can be recombinantly expressed and combined with specific carrier proteins to produce effective vaccines. O-Antigen polysaccharides are typically polydisperse, and carrier proteins can have multiple glycosylation sites. Consequently, recombinant glycoconjugate vaccines have a high structural heterogeneity, making their characterization challenging. Sincedevelopment and quality control processes rely on such character-ization, novel strategies are needed for faster and informative analysis.Here, we present a novel approach employing minimal samplepreparation and ultrahigh-resolution mass spectrometry analysis forprotein terminal sequencing and characterization of the oligosaccharide repeat units of bacterial glycoconjugate vaccines. Threeglycoconjugate vaccine candidates, obtained from the bioconjugation of the O-antigen polysaccharides fromE. coliserotypes O2,O6A, and O25B with the genetically detoxified exotoxin A fromPseudomonas aeruginosa, were analyzed by MALDI-in-source decay(ISD) FT-ICR MS. Protein and glycan ISD fragment ions were selectively detected using 1,5-diaminonaphtalene and a 2,5-dihydroxybenzoic acid/2-hydroxy-5-methoxybenzoic acid mixture (super-DHB) as a MALDI matrix, respectively. The analysis of protein fragments required the absence of salts in the samples, while the presence of salt was key for the detection of sodiated glycanfragments. MS/MS analysis of O-antigen ISD fragments allowed for the detection of specific repeat unit signatures. The developed strategy requires minute sample amounts, avoids the use of chemical derivatizations, and comes with minimal hands-on time allowing for fast corroboration of key structural features of bacterial glycoconjugate vaccines during early- and late-stage developmentProteomic

Large-scale analysis of apolipoprotein CIII glycosylation by ultrahigh resolution mass spectrometry

Apolipoprotein-CIII (apo-CIII) is a glycoprotein involved in lipid metabolism and its levels are associated with cardiovascular disease risk. Apo-CIII sialylation is associated with improved plasma triglyceride levels and its glycosylation may have an effect on the clearance of triglyceride-rich lipoproteins by directing these particles to different metabolic pathways. Large-scale sample cohort studies are required to fully elucidate the role of apo-CIII glycosylation in lipid metabolism and associated cardiovascular disease. In this study, we revisited a high-throughput workflow for the analysis of intact apo-CIII by ultrahigh-resolution MALDI FT-ICR MS. The workflow includes a chemical oxidation step to reduce methionine oxidation heterogeneity and spectrum complexity. Sinapinic acid matrix was used to minimize the loss of sialic acids upon MALDI. MassyTools software was used to standardize and automate MS data processing and quality control. This method was applied on 771 plasma samples from individuals without diabetes allowing for an evaluation of the expression levels of apo-CIII glycoforms against a panel of lipid biomarkers demonstrating the validity of the method. Our study supports the hypothesis that triglyceride clearance may be regulated, or at least strongly influenced by apo-CIII sialylation. Interestingly, the association of apo-CIII glycoforms with triglyceride levels was found to be largely independent of body mass index. Due to its precision and throughput, the new workflow will allow studying the role of apo-CIII in the regulation of lipid metabolism in various disease settings.Proteomic

Serum N-glycome analysis reveals pancreatic cancer disease signatures

Background &Aims Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer type with loco-regional spread that makes the tumor surgically unresectable. Novel diagnostic tools are needed to improve detection of PDAC and increase patient survival. In this study we explore serum proteinN-glycan profiles from PDAC patients with regard to their applicability to serve as a disease biomarker panel. Methods Total serumN-glycome analysis was applied to a discovery set (86 PDAC cases/84 controls) followed by independent validation (26 cases/26 controls) using in-house collected serum specimens. ProteinN-glycan profiles were obtained using ultrahigh resolution mass spectrometry and included linkage-specific sialic acid information.N-glycans were relatively quantified and case-control classification performance was evaluated based on glycosylation traits such as branching, fucosylation, and sialylation. Results In PDAC patients a higher level of branching (OR 6.19,P-value 9.21 x 10(-11)) and (antenna)fucosylation (OR 13.27,P-value 2.31 x 10(-9)) ofN-glycans was found. Furthermore, the ratio of alpha 2,6- vs alpha 2,3-linked sialylation was higher in patients compared to healthy controls. A classification model built with three glycosylation traits was used for discovery (AUC 0.88) and independent validation (AUC 0.81), with sensitivity and specificity values of 0.85 and 0.71 for the discovery set and 0.75 and 0.72 for the validation set. Conclusion SerumN-glycome analysis revealed glycosylation differences that allow classification of PDAC patients from healthy controls. It was demonstrated that glycosylation traits rather than singleN-glycan structures obtained in this clinical glycomics study can serve as a basis for further development of a blood-based diagnostic test.Surgical oncolog

Evaluation of COVID-19 impact on DELAYing diagnostic-therapeutic pathways of lung cancer patients in Italy (COVID-DELAY study): fewer cases and higher stages from a real-world scenario

Introduction: COVID-19 has disrupted the global health care system since March 2020. Lung cancer (LC) patients (pts) represent a vulnerable population highly affected by the pandemic. This multicenter Italian study aimed to evaluate whether the COVID-19 outbreak had an impact on access to cancer diagnosis and treatment of LC pts compared with pre-pandemic time. Methods: Consecutive newly diagnosed LC pts referred to 25 Italian Oncology Departments between March and December 2020 were included. Access rate and temporal intervals between date of symptoms onset and diagnostic and therapeutic services were compared with the same period in 2019. Differences between the 2 years were analyzed using the chi-square test for categorical variables and the Mann\u2013Whitney U test for continuous variables. Results: A slight reduction ( 126.9%) in newly diagnosed LC cases was observed in 2020 compared with 2019 (1523 versus 1637, P = 0.09). Newly diagnosed LC pts in 2020 were more likely to be diagnosed with stage IV disease (P < 0.01) and to be current smokers (someone who has smoked more than 100 cigarettes, including hand-rolled cigarettes, cigars, cigarillos, in their lifetime and has smoked in the last 28 days) (P < 0.01). The drop in terms of new diagnoses was greater in the lockdown period (percentage drop 1212% versus 123.2%) compared with the other months included. More LC pts were referred to a low/medium volume hospital in 2020 compared with 2019 (P = 0.01). No differences emerged in terms of interval between symptoms onset and radiological diagnosis (P = 0.94), symptoms onset and cytohistological diagnosis (P = 0.92), symptoms onset and treatment start (P = 0.40), and treatment start and first radiological revaluation (P = 0.36). Conclusions: Our study pointed out a reduction of new diagnoses with a shift towards higher stage at diagnosis for LC pts in 2020. Despite this, the measures adopted by Italian Oncology Departments ensured the maintenance of the diagnostic-therapeutic pathways of LC pts

Effect of concomitant medications with immune-modulatory properties on the outcomes of patients with advanced cancer treated with immune checkpoint inhibitors: development and validation of a novel prognostic index

Background: Concomitant medications are known to impact on clinical outcomes of patients treated with immune checkpoint inhibitors (ICIs). We aimed weighing the role of different concomitant baseline medications to create a drug-based prognostic score. Methods: We evaluated concomitant baseline medications at immunotherapy initiation for their impact on objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in a single-institution cohort of patients with advanced cancer treated with ICIs (training cohort, N = 217), and a drug-based prognostic score with the drugs resulting significantly impacting the OS was computed. Secondly, we externally validated the score in a large multicenter external cohort (n = 1012). Results: In the training cohort (n = 217), the median age was 69 years (range: 32–89), and the primary tumours were non–small-cell lung cancer (70%), melanoma (14.7%), renal cell carcinoma (9.2%) and others (6%). Among baseline medications, corticosteroids (hazard ratio [HR] = 2.3; 95% confidence interval [CI]: 1.60–3.30), systemic antibiotics (HR = 2.07; 95% CI: 1.31–3.25) and proton-pump inhibitors (PPIs) (HR = 1.57; 95% CI: 1.13–2.18) were significantly associated with OS. The prognostic score was calculated using these three drug classes, defining good, intermediate and poor prognosis patients. Within the training cohort, OS (p < 0.0001), PFS (p < 0.0001) and ORR (p = 0.0297) were significantly distinguished by the score stratification. The prognostic value of the score was also demonstrated in terms of OS (p < 0.0001), PFS (p < 0.0001) and ORR (p = 0.0006) within the external cohort. Conclusion: Cumulative exposure to corticosteroids, antibiotics and PPIs (three likely microbiota-modulating drugs) leads to progressively worse outcomes after ICI therapy. We propose a simple score that can help stratifying patients in routine practice and clinical trials of ICIs

Simultaneous I-O tables balancing at current and constant prices

The balancing of a system of national accounts is normally carried out by balancing first the flows at current prices and then those at constant prices. However, this procedure in two distinct steps makes it impossible to “control” the consistency of the system of deflators. Therefore, a system of simultaneous balancing at current and constant prices is necessary to make it possible to obtain a consistent system of flows at current and constant prices, and of deflators. This paper introduces a simultaneous balancing method as an extension of the methodology described in Nicolardi (1998, 2000) for the simultaneous balancing at current and constant prices of a generic system of economic accounting. The application of the method to the Italian 2005 input-output table has yielded significant results in terms of balancing