CHRONOLOGY OF THE MESSINIAN EVENTS IN THE NORTHERNMOST PART OF THE MEDITERRANEAN: THE GOVONE SECTION (PIEDMONT BASIN, NW ITALY)

In marginal Mediterranean sub-basins the first phase of the Messinian salinity crisis (MSC) is recorded by primary sulfate evaporites (Primary Lower Gypsum unit); in deeper settings, the gypsum makes lateral transition into shales and marls usually barren of calcareous fossils that can hamper the identification of the MSC onset. The Govone section (Piedmont Basin, NW Italy) represents an opportunity to examine in detail the pre-MSC interval and the transition to the first stage of the MSC in a relatively deep marginal basin in the northernmost sector of the Mediterranean. We provide herein an age model for the Govone section, based on an integrated stratigraphic study, including cycloctratigraphy, magnetostratigraphy and micropaleontology (foraminifera and calcareous nannofossils) of the pre-MSC interval and the transition to the MSC. Chron C3An.1n has not been recognized in the study succession, most likely due to early diagenetic processes. Thus, the last occurrence of Turborotalita multiloba occurring two lithological cycles above the second influx of G. scitula, is the event that best approximate the MSC onset and is consistently recorded across the Piedmont Basin, with higher abundance respect to coeval Mediterranean successions. The calibration of the lithological cyclicity by means of these two bioevents allowed to recognize that, unlike other Mediterranean sections, the disappearance of calcareous microfossils occurs before the MSC onset, probably, in response of diagenetic processes favouring the dissolution of calcareous shells

<i>Structores amphitheatri</i>: a proposito dell’anfiteatro di <i>Forum Traiani</i> (<i>Sardinia</i>)

Gli structores, talora richiamati nella documentazione epigrafica, coordinano le maestranze e le forniture di materiali e di servizi necessari alla realizzazione del progetto edilizio di un architectus, in particolare per quelle strutture monumentali destinate all’ornatus civitatis, ma anche ad una precisa funzionalità nell’ambito delle direttrici urbanologiche della città romana. Si vuole proporre in questa sede un’analisi ricostruttiva dei cantieri edilizi, con il relativo personale tecnico, attivati rispettivamente in funzione della costruzione e dell’ampliamento del secondo edificio per gli spettacoli della Sardinia, per le sue dimensioni, l’anfiteatro di Forum Traiani, fatto oggetto di scavo archeologico fra i mesi di febbraio e settembre 2008, a cura della Soprintendenza archeologica della Sardegna in collaborazione con l’Università degli Studi di Sassari, il Comune di Fordongianus e la Casa Circondariale di Oristano

Decreasing hospital burden of COVID-19 during the first wave in Regione Lombardia: an emergency measures context

Abstract: Background: The aim of this study is to quantify the hospital burden of COVID-19 during the first wave and how it changed over calendar time; to interpret the results in light of the emergency measures introduced to manage the strain on secondary healthcare. Methods: This is a cohort study of hospitalised confirmed cases of COVID-19 admitted from February–June 2020 and followed up till 17th July 2020, analysed using a mixture multi-state model. All hospital patients with confirmed COVID-19 disease in Regione Lombardia were involved, admitted from February–June 2020, with non-missing hospital of admission and non-missing admission date. Results: The cohort consists of 40,550 patients hospitalised during the first wave. These patients had a median age of 69 (interquartile range 56–80) and were more likely to be men (60%) than women (40%). The hospital-fatality risk, averaged over all pathways through hospital, was 27.5% (95% CI 27.1–28.0%); and steadily decreased from 34.6% (32.5–36.6%) in February to 7.6% (6.3–10.6%) in June. Among surviving patients, median length of stay in hospital was 11.8 (11.6–12.3) days, compared to 8.1 (7.8–8.5) days in non-survivors. Averaged over final outcomes, median length of stay in hospital decreased from 21.4 (20.5–22.8) days in February to 5.2 (4.7–5.8) days in June. Conclusions: The hospital burden, in terms of both risks of poor outcomes and lengths of stay in hospital, has been demonstrated to have decreased over the months of the first wave, perhaps reflecting improved treatment and management of COVID-19 cases, as well as reduced burden as the first wave waned. The quantified burden allows for planning of hospital beds needed for current and future waves of SARS-CoV-2 i

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

Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p &lt; .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p &lt; .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come