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This paper draws on a subsample (N = 851) of respondents to ITA.LI—Italian Lives—a recently established panel study on a probability sample of individuals aged 16+ living in Italy—to track changes in the affective (positive and negative emotions such as energy and sadness) and cognitive (life satisfaction) components of well-being during different COVID-19 policy phases, classified according to the severity of key government responses. An event-study design is employed, which uses mixed-effects ordered logistic models to investigate the change in SWB scores. Given the nested nature of the data, multilevel modeling is chosen as the most appropriate method of analysis. The results reveal the levels of affective and cognitive well-being were significantly lower during the lockdown period than before the pandemic outbreak potentially reflecting both the direct effects of the confinement and other potential sources of distress, such as trends in infection rates and related media alarm. Once the lockdown was lifted, there was no evidence of an immediate and general improvement in well-being. In the following policy phase, with the lifting of most containment measures, there were significant signs of full recovery concerning energy, but the scores for the other well-being components remained relatively lower than those observed before the onset of COVID-19.

Le Sindromi Mielodisplastiche (MDS) sono un gruppo eterogeneo di neoplasie mieloidi con esito clinico variabile e un aumentato rischio di progressione a Leucemia Mieloide Acuta (AML). Data la loro eterogeneità, l’uso di sistemi di classificazione e stratificazione è di fondamentale importanza per identificare il sottotipo di malattia e per valutare la prognosi dei pazienti, tuttavia, i sistemi attuali falliscono nel prevedere chi risponderà alla terapia con agenti ipometilanti (HMA). Diversi studi hanno sottolineato il ruolo della deregolazione immune nella patogenesi e progressione delle MDS. Tuttavia, l’informazione immunologica è tuttora omessa dai fattori per la stratificazione del rischio dal momento che non esiste ancora un metodo standard per la valutazione dello stato immunitario dei pazienti. L’aggiunta di dati comprensivi della funzionalità immunologica agli attuali scores potrebbe fornire un aiuto nel definire la stratificazione del rischio e nel predire la risposta ai trattamenti. Nel primo progetto, abbiamo utilizzato la tecnica di citometria a flusso per effettuare un’analisi della composizione immune di midollo (BM) e sangue periferico (PB) di 154 pazienti con MDS o AML post-MDS, investigando linfociti T, cellule Natural Killer (NK) e cellule mieloidi prima e dopo trattamento con HMA. Abbiamo analizzato la distribuzione e il fenotipo dei vari sottotipi di cellule immunitarie ed abbiamo implementato una pipeline per raggruppare i pazienti in base alle loro caratteristiche immunologiche. Dopodiché, abbiamo ulteriormente caratterizzato ogni gruppo immunologico integrando dati di bulk RNAseq provenienti dalle cellule CD34+ isolate da midollo dei pazienti, dati mutazionali e clinici, effettuando in questo modo un’analisi multi-omica. Nel secondo e terzo progetto, ci siamo invece focalizzati rispettivamente sulla caratterizzazione immunitaria delle MDS con disfunzione di p53 e delle MDS mutate nel gene SF3B1, sempre combinando i dati di immunofenotipo, Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid neoplasms with variable clinical outcomes and an increased risk of progression to acute myeloid leukemia (AML). Given this heterogeneity, the use of classifications and scoring systems is of fundamental importance to identify the disease subtype and to evaluate patient’s prognosis but fails in predicting patients who will respond to hypomethylating agents (HMAs), which represent the first line treatment for high-risk MDS patients. Several studies have underlined the role of immune dysregulation in MDS pathogenesis and progression. However, immunologic information is currently omitted from risk scores because there is still no standard method for evaluating patient’s immune status. The addition of comprehensive immunologic data to prognostic models could further help to refine risk stratification and predict therapy response. In the first project included in my thesis, we took advantage of high-dimensional flow cytometry to perform a comprehensive analysis of the immunologic landscape in bone marrow (BM) and peripheral blood (PB) of 154 MDS and AML post-MDS patients, investigating T lymphocytes, Natural Killer (NK) and Myeloid cells before and after HMA treatment. We analyzed the immune cell subsets distribution and phenotype with both manual gating and Phenograph algorithm, and we implemented an unsupervised pipeline to clusterize MDS patients according to their immune features. Then, we further characterized each immunological group by integrating bulk RNA-seq data of BM CD34+ cells isolated from patients, DNA mutations and clinical data, thus performing a multi-omics analysis. In the second and third projects, we instead focused our attention on the immune characterization of MDS with dysfunction of p53 and SF3B1mut MDS, respectively, always combining immunophenotyping with transcriptomic and clinical data. Classical manual gating analysis revealed that in advanced stages of the disease both BM a

La Società del Giardino è il più antico club della città di Milano, aperto nel 1783 ad opera di Francesco Bolchini e di alcuni altri esponenti del ceto civile cittadino. Nei primi anni vi fu notevole sviluppo, e più volte è ricordato nelle poesie Carlo Porta, il cantore della Milano tra '700 e '800.

Il contributo presenta la facoltà di scienze della formazione dell'Università Cattolica del Sacro Cuore che opera su tre sedi (Milano, Brescia, PIacenza) con 12 doversi corsi di Laurea. Se ne descrive brevemente la storia, l'evoluzioni e le caratteristiche principali che ne ispirano l'azione.

La presente riflessione muove dal presupposto che essere cittadini attivi, capaci cioè di comprendere, agire e modellare il proprio territorio, in grado di avvalersi delle risorse materiali e immateriali disponibili e di nutrire il sentimento di appartenenza è in primo luogo una questione di conoscenza locale. La conoscenza locale può diventare anche una importante forma di autoriconoscimento, uno strumento per l’elaborazione di visioni territoriali alternative e di una propria “voce”, di individuazione di forme originali di sviluppo sostenibile e di risposta alla vulnerabilità dei territori dovuta al cambiamento climatico, agli eventi naturali, agli eccessi della globalizzazione e alle guerre.

Nella formazione di insegnanti e educatori i temi dell’educazione e della cittadinanza rivestono un ruolo essenziale e costituiscono un cantiere di rifl essione e di sperimentazione in costante evoluzione. Il volume costituisce al tempo stesso l’esito e la testimonianza di un progetto di terza missione su queste tematiche tra la Facoltà di Scienze della formazione dell’Università Cattolica del Sacro Cuore di Milano e la Faculté des Sciences de l’Education de l’Université Notre Dame d’Haïti a Jacmel.

La présente réflexion découle du principe qu’être citoyens actifs, c’est-à-dire capables de comprendre, agir et modeler son propre territoire, en état de se servir des ressources matérielles et immatérielles disponibles et d’alimenter le sentiment d’appartenance est d’abord une question de connaissance locale. La connaissance locale peut devenir une forme importante d’autoreconnaissance, un instrument pour l’élaboration de visions territoriales alternatives et d’une propre « voix », d’individuation de formes originelles de développement durable et de réponse à la vulnérabilité des territoires due au changement climatique, aux évènements naturels, aux excès de la globalisation et aux conflits.

In occasione dei 240 anni dalla fondazione, il volume avvia studi di ricerca storica sul primo club di svago e divertimento sorto a Milano nella seconda metà del XVIII secolo, approfondendo in particolare gli elementi legati alla composizione e all'estrazione sociale della compagine dei soci, all'organizzazione societaria, alla definizione del modello di sociabilità, ai primi regolamenti.

Most individuals yearn to experience interpersonal closeness and connection to others at work. Would those experiences be related to lower work-family conflict (WFC), which in turn would be related to enhanced wellbeing? In the current study we build on job demands-resources (J-DR) and self-determination (SDT) theories to investigate differences across the life course in the effect of communion job resources (employee involvement and supportive leadership) and job hindrance demands (surface acting) on important dimensions of employee wellbeing (namely mental health, sleep quality and work-engagement). Moreover, we study the proportion of the total effect of job demands and resources on individual outcomes that is mediated by the subjective assessment of WFC. Structural equation modelling (SEM) analysis, which draws on the 6th European Working Conditions Survey (N = 35,377 employees in 35 countries), reveals that communion job resources are associated with lower WFC, which in turn is associated with enhanced wellbeing. Conversely, communion job hindrance demands and structural demands (long working hours) are related to heightened WFC, which is translated into diminished wellbeing. The model is significant for both men and women from all age groups, but parameter estimates magnitude are stronger for women aged 50 +. Implications of the findings are discussed.

PURPOSE: Synthetic data are artificial data generated without including any real patient information by an algorithm trained to learn the characteristics of a real source data set and became widely used to accelerate research in life sciences. We aimed to (1) apply generative artificial intelligence to build synthetic data in different hematologic neoplasms; (2) develop a synthetic validation framework to assess data fidelity and privacy preservability; and (3) test the capability of synthetic data to accelerate clinical/translational research in hematology. METHODS: A conditional generative adversarial network architecture was implemented to generate synthetic data. Use cases were myelodysplastic syndromes (MDS) and AML: 7,133 patients were included. A fully explainable validation framework was created to assess fidelity and privacy preservability of synthetic data. RESULTS: We generated MDS/AML synthetic cohorts (including information on clinical features, genomics, treatment, and outcomes) with high fidelity and privacy performances. This technology allowed resolution of lack/incomplete information and data augmentation. We then assessed the potential value of synthetic data on accelerating research in hematology. Starting from 944 patients with MDS available since 2014, we generated a 300% augmented synthetic cohort and anticipated the development of molecular classification and molecular scoring system obtained many years later from 2,043 to 2,957 real patients, respectively. Moreover, starting from 187 MDS treated with luspatercept into a clinical trial, we generated a synthetic cohort that recapitulated all the clinical end points of the study. Finally, we developed a website to enable clinicians generating high-quality synthetic data from an existing biobank of real patients. CONCLUSION: Synthetic data mimic real clinical-genomic features and outcomes, and anonymize patient information. The implementation of this technology allows to increase the scientific

Purpose: The service configuration with distinct child and adolescent mental health services (CAMHS) and adult mental health services (AMHS) may be a barrier to continuity of care. Because of a lack of transition policy, CAMHS clinicians have to decide whether and when a young person should transition to AMHS. This study describes which characteristics are associated with the clinicians’ advice to continue treatment at AMHS. Methods: Demographic, family, clinical, treatment, and service-use characteristics of the MILESTONE cohort of 763 young people from 39 CAMHS in Europe were assessed using multi-informant and standardized assessment tools. Logistic mixed models were fitted to assess the relationship between these characteristics and clinicians’ transition recommendations. Results: Young people with higher clinician-rated severity of psychopathology scores, with self- and parent-reported need for ongoing treatment, with lower everyday functional skills and without self-reported psychotic experiences were more likely to be recommended to continue treatment. Among those who had been recommended to continue treatment, young people who used psychotropic medication, who had been in CAMHS for more than a year, and for whom appropriate AMHS were available were more likely to be recommended to continue treatment at AMHS. Young people whose parents indicated a need for ongoing treatment were more likely to be recommended to stay in CAMHS. Conclusion: Although the decision regarding continuity of treatment was mostly determined by a small set of clinical characteristics, the recommendation to continue treatment at AMHS was mostly affected by service-use related characteristics, such as the availability of appropriate services.

This paper uses data from four waves of the Survey of Health, Ageing and Retirement in Europe (SHARE) and investigates the effect of job quality on CASP-12, which is a measure of quality of life and wellbeing, on a large and longitudinal sample (30,473 observations nested within 21,278 individuals) of workers aged 50-64 years in 14 European countries. Building on the different theoretical models of work-related stress and wellbeing and using Self-Organizing Map, sampled workers were grouped into different job quality clusters. Then, multilevel and growth curve modelling was used to examine: i) the effect of cluster membership on CASP-12; ii) whether protracted membership in different job quality clusters could produce cumulative effects on CASP-12; and iii) the moderating effect of the national unemployment rate. Findings indicate that a wellbeing gradient exists in which higher CASP-12 scores result from membership in the better job quality cluster; however, there is no evidence of cumulative effects of job quality on CASP-12. Finally, analyses confirm country-specific relationships between job quality and quality of life and wellbeing; namely, they indicate that the wellbeing gradient associated with better job quality is steeper in countries with higher unemployment rates.

This volume aims to provide an overview of all aspects of the design and implementation of the first wave of the Italian Lives survey. Specifically, the volume is divided into eight chapters. The first chapter briefly describes the survey, its purposes, and its potential. The second chapter illustrates the procedures inspired by the principles of the survey methodology that have been applied to carry out the first wave of data collection. The third chapter analyses the structure and content of the questionnaires. The fourth chapter provides a description of the pre-field, pre-testing, and piloting activities. The fifth chapter explains the data collection procedures. The sixth chapter describes the data management and data cleaning processes. The seventh chapter illustrates the processes of data management and missing imputation. Finally, the eighth chapter sets out the ethical requirements.

In recent years, a great deal of effort has been undertaken with regards to treatment of pathologies at the level of the central nervous system (CNS). Here, the presence of the blood-brain barrier acts as an obstacle to the delivery of potentially effective drugs and makes accessibility to, and treatment of, the CNS one of the most significant challenges in medicine. In this Roadmap article, we present the status of the timeliest developments in the field, and identify the outstanding challenges and opportunities that exist. The format of the Roadmap, whereby experts in each discipline share their viewpoint and present their vision, reflects the dynamic and multidisciplinary nature of this research area, and is intended to generate dialogue and collaboration across traditional subject areas. It is stressed here that this article is not intended to act as a comprehensive review article, but rather an up-to-date and forward-looking summary of research methodologies pertaining to the treatment of pathologies at the level of the CNS.

Purpose: The present study connects the literature on sustainable HRM with that on employability to investigate the relationship between sustainability-oriented human resource actions and organizational outcomes. More specifically, this study explores how training for employability affects the employer–employee relationship and employee retention. Furthermore, this study considers competitive intensity as a potential moderator in these relationships. Design/methodology/approach: The analyses draw on the fourth European Company Survey (ECS 2019) with a sample of 21?869 firms with more than ten employees. Two separate logistic regression models were used to test the hypothesis. Findings: The results show that training for employability contributes to improving the employer–employee relationship and that competitive intensity positively shapes this relationship. Contextually, training for employability reduces the overall employee retention of the firm. Originality/value: Although this study supports the potential win–win nature of employability support, especially for companies that operate in competitive markets and an uncertain environment, it also highlights the existence of paradoxical sustainability tensions that should be managed by employers.

Purpose: Myelodysplastic syndromes (MDS) are heterogeneous myeloid neoplasms in which a risk-adapted treatment strategy is needed. Recently, a new clinical-molecular prognostic model, the Molecular International Prognostic Scoring System (IPSS-M) was proposed to improve the prediction of clinical outcome of the currently available tool (Revised International Prognostic Scoring System [IPSS-R]). We aimed to provide an extensive validation of IPSS-M. Methods: A total of 2,876 patients with primary MDS from the GenoMed4All consortium were retrospectively analyzed. Results: IPSS-M improved prognostic discrimination across all clinical end points with respect to IPSS-R (concordance was 0.81 v 0.74 for overall survival and 0.89 v 0.76 for leukemia-free survival, respectively). This was true even in those patients without detectable gene mutations. Compared with the IPSS-R based stratification, the IPSS-M risk group changed in 46% of patients (23.6% and 22.4% of subjects were upstaged and downstaged, respectively).In patients treated with hematopoietic stem cell transplantation (HSCT), IPSS-M significantly improved the prediction of the risk of disease relapse and the probability of post-transplantation survival versus IPSS-R (concordance was 0.76 v 0.60 for overall survival and 0.89 v 0.70 for probability of relapse, respectively). In high-risk patients treated with hypomethylating agents (HMA), IPSS-M failed to stratify individual probability of response; response duration and probability of survival were inversely related to IPSS-M risk.Finally, we tested the accuracy in predicting IPSS-M when molecular information was missed and we defined a minimum set of 15 relevant genes associated with high performance of the score. Conclusion: IPSS-M improves MDS prognostication and might result in a more effective selection of candidates to HSCT. Additional factors other than gene mutations can be involved in determining HMA sensitivity. The definition of a minimum set of relevan

BACKGROUND: Sex is a major source of diversity among patients and a sex-informed approach is becoming a new paradigm in precision medicine. We aimed to describe sex diversity in myelodysplastic syndromes in terms of disease genotype, phenotype, and clinical outcome. Moreover, we sought to incorporate sex information into the clinical decision-making process as a fundamental component of patient individuality. METHODS: In this multicentre, observational cohort study, we retrospectively analysed 13 284 patients aged 18 years or older with a diagnosis of myelodysplastic syndrome according to 2016 WHO criteria included in the EuroMDS network (n=2025), International Working Group for Prognosis in MDS (IWG-PM; n=2387), the Spanish Group of Myelodysplastic Syndromes registry (GESMD; n=7687), or the Düsseldorf MDS registry (n=1185). Recruitment periods for these cohorts were between 1990 and 2016. The correlation between sex and genomic features was analysed in the EuroMDS cohort and validated in the IWG-PM cohort. The effect of sex on clinical outcome, with overall survival as the main endpoint, was analysed in the EuroMDS population and validated in the other three cohorts. Finally, novel prognostic models incorporating sex and genomic information were built and validated, and compared to the widely used revised International Prognostic Scoring System (IPSS-R). This study is registered with ClinicalTrials.gov, NCT04889729. FINDINGS: The study included 7792 (58·7%) men and 5492 (41·3%) women. 10 906 (82·1%) patients were White, and race was not reported for 2378 (17·9%) patients. Sex biases were observed at the single-gene level with mutations in seven genes enriched in men (ASXL1, SRSF2, and ZRSR2 p<0·0001 in both cohorts; DDX41 not available in the EuroMDS cohort vs p=0·0062 in the IWG-PM cohort; IDH2 p<0·0001 in EuroMDS vs p=0·042 in IWG-PM; TET2 p=0·031 vs p=0·035; U2AF1 p=0·033 vs p<0·0001) and mutations in two genes were enriched in women (DNMT3A p<0·000

PURPOSEMyelodysplastic syndromes (MDS) are heterogeneous myeloid neoplasms in which a risk-adapted treatment strategy is needed. Recently, a new clinical-molecular prognostic model, the Molecular International Prognostic Scoring System (IPSS-M) was proposed to improve the prediction of clinical outcome of the currently available tool (Revised International Prognostic Scoring System [IPSS-R]). We aimed to provide an extensive validation of IPSS-M.METHODSA total of 2,876 patients with primary MDS from the GenoMed4All consortium were retrospectively analyzed.RESULTSIPSS-M improved prognostic discrimination across all clinical end points with respect to IPSS-R (concordance was 0.81 v 0.74 for overall survival and 0.89 v 0.76 for leukemia-free survival, respectively). This was true even in those patients without detectable gene mutations. Compared with the IPSS-R based stratification, the IPSS-M risk group changed in 46% of patients (23.6% and 22.4% of subjects were upstaged and downstaged, respectively).In patients treated with hematopoietic stem cell transplantation (HSCT), IPSS-M significantly improved the prediction of the risk of disease relapse and the probability of post-transplantation survival versus IPSS-R (concordance was 0.76 v 0.60 for overall survival and 0.89 v 0.70 for probability of relapse, respectively). In high-risk patients treated with hypomethylating agents (HMA), IPSS-M failed to stratify individual probability of response; response duration and probability of survival were inversely related to IPSS-M risk.Finally, we tested the accuracy in predicting IPSS-M when molecular information was missed and we defined a minimum set of 15 relevant genes associated with high performance of the score.CONCLUSIONIPSS-M improves MDS prognostication and might result in a more effective selection of candidates to HSCT. Additional factors other than gene mutations can be involved in determining HMA sensitivity. The definition of a minimum set of relevant genes may

Myelodysplastic syndromes (MDS) are a clonal disease arising from hematopoietic stem cells, that are characterized by ineffective hematopoiesis (leading to peripheral blood cytopenia) and by an increased risk of evolution into acute myeloid leukemia. MDS are driven by a complex combination of genetic mutations that results in heterogeneous clinical phenotype and outcome. Genetic studies have enabled the identification of a set of recurrently mutated genes which are central to the pathogenesis of MDS and can be organized into a limited number of cellular pathways, including RNA splicing (SF3B1, SRSF2, ZRSR2, U2AF1 genes), DNA methylation (TET2, DNMT3A, IDH1/2), transcription regulation (RUNX1), signal transduction (CBL, RAS), DNA repair (TP53), chromatin modification (ASXL1, EZH2), and cohesin complex (STAG2). Few genes are consistently mutated in >10% of patients, whereas a long tail of 40–50 genes are mutated in <5% of cases. At diagnosis, the majority of MDS patients have 2–4 driver mutations and hundreds of background mutations. Reliable genotype/phenotype relationships were described in MDS: SF3B1 mutations are associated with the presence of ring sideroblasts and more recent studies indicate that other splicing mutations (SRSF2, U2AF1) may identify distinct disease categories with specific hematological features. Moreover, gene mutations have been shown to influence the probability of survival and risk of disease progression and mutational status may add significant information to currently available prognostic tools. For instance, SF3B1 mutations are predictors of favourable prognosis, while driver mutations of other genes (such as ASXL1, SRSF2, RUNX1, TP53) are associated with a reduced probability of survival and increased risk of disease progression. In this article, we review the most recent advances in our understanding of the genetic basis of myelodysplastic syndromes and discuss its clinical relevance.