The association of economic and cultural capital with the NEET rate: differential geographical and temporal patterns

AbstractUsing data from 103 Italian provinces, we investigated the relationship between local/regional development, and NEET. We constructed an indicator of cultural capital and another of economic capital and we studied their relation with the NEET rate. Covariance Structure Analysis with Generalized Least Squares estimation was employed, considering a three time-points retrospective model. Results indicate a consistent protective effect of the economic capital on the NEET rate, both in the short run (2 years) and in the medium run (10 years). However, this effect has been obtained in the Central provinces (at 2 and 10 years) and Southern provinces (at 10 years), but not in the Northern provinces. A mediation analysis indicated that, historically, the cultural capital may partly mediate the effect of the economic capital. We did not detect a significant direct effect of the cultural capital on the NEET rate, which is strongly mediated by the action of the economic capital. Together, these results denote that the economic capital is a strong predictor of NEET, but not in very competitive economic areas

Fragilità, credibilità, controfattuale

Riassunto: Nell’ultimo decennio il p-value è stato sottoposto a notevoli critiche soprattutto per l’uso che se ne fa per raggiungere una conclusione dicotomica circa la significatività del risultato sperimentale (significativo o non significativo). Pertanto, da una parte il p-value è stato sostituito con approcci differenti, dall’altra è stato affiancato da alcune procedure diagnostiche, tra le quali figurano la fragilità e la credibilità, che hanno il compito di rafforzare o meno la conclusione. La fragilità e l’indice che la misura presentano aspetti di debolezza metodologica. D’altro canto, l’indice di credibilità sembra idoneo per dare o meno supporto alla conclusione e per rafforzare o sostituire l’indice di fragilità, dato che misura la credibilità del risultato osservato quantificando l’informazione a priori necessaria per ribaltare il risultato stesso. Il particolare meccanismo delle due procedure, che si fonda su quanto dovrebbe accadere per cambiare la conclusione, suggerisce di inserire le medesime nella prospettiva controfattuale considerandole come nuovi strumenti per la sua misura quantitativa. In questo contributo si presenta questa prospettiva, con particolare riferimento al campo applicativo delle scienze psicologiche.Parole chiave: p-value; Indice di fragilità; Distribuzioni a priori; Indice di credibilità; Prospettiva controfattuale  Fragility, credibility and counterfactualityAbstract: In the last decade, scientific reliance on p-values, especially when used to determine in a dichotomic manner whether a scientific result is significant or not, has been strongly criticized. As a consequence, p-values are sometimes replaced by other statistical tools, or supplemented by complementary procedures such as tests for fragility and credibility, which lend further support or challenge the conclusion. The fragility index presents some methodological weaknesses of its own. The credibility index proposed in the literature seems to provide a particularly useful supplement for p-values as well as for the fragility index, considering that it assesses the reliability of the result obtained by quantifying the a priori information needed to overturn the result. Both procedures rely on what would need to happen in order to modify the conclusion. This suggests that they can be considered as valuable new tools for quantitative measurement within a counterfactual framework. In our contribution we present this perspective, with reference to the psychological sciences.Keywords: p-value; Fragility Index; Priors/Posteriors; Credibility Index; Counterfactual Perspectiv

Effectiveness of a phone-based nurse monitoring assessment and intervention for chemotherapy-related toxicity: A randomized multicenter trial

PurposeAnticancer treatment-related toxicities can impact morbidity and mortality, hamper the administration of treatment, worsen the quality of life and increase the burden on the healthcare system. Therefore, their prompt identification is crucial. NICSO (Italian Network for Supportive Care in Cancer) conducted a nationwide randomized trial to evaluate the role of a planned, weekly phone-based nurse monitoring intervention to prevent and treat chemotherapy, targeted therapy- and immunotherapy-related toxicities. Here, we report the results from the chemotherapy arm. MethodsThis was a nationwide, randomized, open-label trial conducted among 29 Italian centers (NCT04726020) involving adult patients with breast, colon, or lung cancer and a life expectancy >= 6 months receiving adjuvant chemotherapy. Patients received either a weekly nurse monitoring phone call and an educational leaflet reporting practical advice about prevention and treatment of toxicities (experimental group) or the educational leaflet only (control group). ResultsThe addition of a nurse monitoring intervention may help reduce time spent with severe toxicities (grade >= 3), particularly those less frequently reported in clinical practice, such as fatigue. When considering grade 1-2 AEs, times with mild/moderate diarrhea, mucositis, fatigue and pain were shorter in the experimental arm. Time spent without AEs was significantly longer in the experimental arms for all the toxicities. The requirement for special medical attention was comparable between groups. ConclusionThis study suggests the need for implementing a better system of toxicity assessment and management for patients treated with adjuvant chemotherapy to promote effective preventive and/or therapeutic intervention against these events

Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines

Background & aims: Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), composed of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC. Methods: After reviewing the published literature, a Delphi methodology was used to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of ≥80%. Results: The DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery. On the basis of current evidence, endoscopic, surgical, and oncologic treatment of eoCRC should not differ from later-onset CRC, except for individuals with pathogenic or likely pathogenic germline variants. The evidence on chemotherapy is not sufficient to recommend changes to established therapeutic protocols. Fertility preservation and sexual health are important to address in eoCRC survivors. The DIRECt group highlighted areas with knowledge gaps that should be prioritized in future research efforts, including age at first screening for the general population, use of fecal immunochemical tests, chemotherapy, endoscopic therapy, and post-treatment surveillance for eoCRC patients. Conclusions: The DIRECt group produced the first consensus recommendations on eoCRC. All statements should be considered together with the accompanying comments and literature reviews. We highlighted areas where research should be prioritized. These guidelines represent a useful tool for clinicians caring for patients with eoCRC

An explainable model of host genetic interactions linked to COVID-19 severity

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as "Respiratory or thoracic disease", supporting their link with COVID-19 severity outcome.A multifaceted computational strategy identifies 16 genetic variants contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing dataset of a cohort of Italian patients

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Assessing the inter-rater agreement for ordinal data through weighted indexes

Assessing the inter-rater agreement between observers, in the case of ordinal variables, is an important issue in both the statistical theory and biomedical applications. Typically, this problem has been dealt with the use of Cohen's weighted kappa, which is a modification of the original kappa statistic, proposed for nominal variables in the case of two observers. Fleiss (1971) put forth a generalization of kappa in the case of multiple observers, but both Cohen's and Fleiss' kappa could have a paradoxical behavior, which may lead to a difficult interpretation of their magnitude. In this paper, a modification of Fleiss' kappa, not affected by paradoxes, is proposed, and subsequently generalized to the case of ordinal variables. Monte Carlo simulations are used both to testing statistical hypotheses and to calculating percentile and bootstrap-t confidence intervals based on this statistic. The normal asymptotic distribution of the proposed statistic is demonstrated. Our results are applied to the classical Holmquist et al.'s (1967) dataset on the classification, by multiple observers, of carcinoma in situ of the uterine cervix. Finally, we generalize the use of s∗ to a bivariate case