Per una rilettura di «Le Roman expérimental» di Émile Zola

A lungo ritenuto architrave di teoria letteraria per i Rougon-Macquart, Le Roman expérimental è il saggio più noto di Émile Zola, che in esso definisce la propria posizione nei riguardi della concezione del romanzo e degli aspetti morali e sociali del ruolo dello scrittore. Benché di norma sia considerato indispensabile per parlare di Zola, il testo in Italia sembra a tutt’oggi molto più citato che letto, spesso non senza qualche forzatura o fraintendimento, in particolar modo quando studiosi..

Level 2 processor and auxiliary data for ESA Version 8 final full mission analysis of MIPAS measurements on ENVISAT

High quality long-term data sets of altitude-resolved measurements of the atmospheric composition are important because they can be used both to study the evolution of the atmosphere and as a benchmark for future missions. For the final ESA reprocessing of MIPAS (Michelson Interferometer for Passive Atmospheric Sounding) on ENVISAT (ENViromental SATellite) data, numerous improvements were implemented in the Level 2 (L2) processor Optimised Retrieval Model (ORM) version 8.22 (V8) and its auxiliary data. The implemented changes involve all aspects of the processing chain, from the modelling of the measurements with the handling of the horizontal inhomogeneities along the line of sight to the use of the optimal estimation technique to retrieve the minor species, from a more sensitive approach to detecting the spectra affected by clouds to a refined method for identifying low quality products. Improvements in the modelling of the measurements were also obtained with an update of the used spectroscopic data and of the databases providing the a priori knowledge of the atmosphere. The HITRAN_mipas_pf4.45 spectroscopic database was finalised with new spectroscopic data verified with MIPAS measurements themselves, while recently measured cross-sections were used for the heavy molecules. The Level 2 Initial Guess (IG2) data set, containing the climatology used by the MIPAS L2 processor to generate the initial guess and interfering species profiles when the retrieved profiles from previous scans are not available, was improved taking into account the diurnal variation of the profiles defined using climatologies from both measurements and models. Horizontal gradients were generated using the ECMWF ERA-Interim data closest in time and space to the MIPAS data. Further improvements in the L2 V8 products derived from the use of the L1b V8 products, which were upgraded to reduce the instrumental temporal drift and to handle the abrupt changes in the calibration gain. The improvements introduced into the ORM V8 L2 processor and its upgraded auxiliary data, together with the use of the L1b V8 products, lead to the generation of the MIPAS L2 V8 products, which are characterised by an increased accuracy, better temporal stability and a greater number of retrieved species

Level 2 processor and auxiliary data for ESA Version 8 final full mission analysis of MIPAS measurements on ENVISAT

High quality long-term data sets of altitude-resolved measurements of the atmospheric composition are important because they can be used both to study the evolution of the atmosphere and as a benchmark for future missions. For the final ESA reprocessing of MIPAS (Michelson Interferometer for Passive Atmospheric Sounding) on ENVISAT (ENViromental SATellite) data, numerous improvements were implemented in the Level 2 (L2) processor Optimised Retrieval Model (ORM) version 8.22 (V8) and its auxiliary data. The implemented changes involve all aspects of the processing chain, from the modelling of the measurements with the handling of the horizontal inhomogeneities along the line of sight to the use of the optimal estimation technique to retrieve the minor species, from a more sensitive approach to detecting the spectra affected by clouds to a refined method for identifying low quality products. Improvements in the modelling of the measurements were also obtained with an update of the used spectroscopic data and of the databases providing the a priori knowledge of the atmosphere. The HITRAN_mipas_pf4.45 spectroscopic database was finalised with new spectroscopic data verified with MIPAS measurements themselves, while recently measured cross-sections were used for the heavy molecules. The Level 2 Initial Guess (IG2) data set, containing the climatology used by the MIPAS L2 processor to generate the initial guess and interfering species profiles when the retrieved profiles from previous scans are not available, was improved taking into account the diurnal variation of the profiles defined using climatologies from both measurements and models. Horizontal gradients were generated using the ECMWF ERA-Interim data closest in time and space to the MIPAS data. Further improvements in the L2 V8 products derived from the use of the L1b V8 products, which were upgraded to reduce the instrumental temporal drift and to handle the abrupt changes in the calibration gain. The improvements introduced into the ORM V8 L2 processor and its upgraded auxiliary data, together with the use of the L1b V8 products, lead to the generation of the MIPAS L2 V8 products, which are characterised by an increased accuracy, better temporal stability and a greater number of retrieved species

Effect of Lactoferrin on Clinical Outcomes of Hospitalized Patients with COVID-19: The LAC Randomized Clinical Trial

: As lactoferrin is a nutritional supplement with proven antiviral and immunomodulatory abilities, it may be used to improve the clinical course of COVID-19. The clinical efficacy and safety of bovine lactoferrin were evaluated in the LAC randomized double-blind placebo-controlled trial. A total of 218 hospitalized adult patients with moderate-to-severe COVID-19 were randomized to receive 800 mg/die oral bovine lactoferrin (n = 113) or placebo (n = 105), both given in combination with standard COVID-19 therapy. No differences in lactoferrin vs. placebo were observed in the primary outcomes: the proportion of death or intensive care unit admission (risk ratio of 1.06 (95% CI 0.63-1.79)) or proportion of discharge or National Early Warning Score 2 (NEWS2) ≤ 2 within 14 days from enrollment (RR of 0.85 (95% CI 0.70-1.04)). Lactoferrin showed an excellent safety and tolerability profile. Even though bovine lactoferrin is safe and tolerable, our results do not support its use in hospitalized patients with moderate-to-severe COVID-19

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

Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes

Carriers of single pathogenic variants of the CFTR (cystic fibrosis transmembrane conductance regulator) gene have a higher risk of severe COVID-19 and 14-day death. The machine learning post-Mendelian model pinpointed CFTR as a bidirectional modulator of COVID-19 outcomes. Here, we demonstrate that the rare complex allele [G576V;R668C] is associated with a milder disease via a gain-of-function mechanism. Conversely, CFTR ultra-rare alleles with reduced function are associated with disease severity either alone (dominant disorder) or with another hypomorphic allele in the second chromosome (recessive disorder) with a global residual CFTR activity between 50 to 91%. Furthermore, we characterized novel CFTR complex alleles, including [A238V;F508del], [R74W;D1270N;V201M], [I1027T;F508del], [I506V;D1168G], and simple alleles, including R347C, F1052V, Y625N, I328V, K68E, A309D, A252T, G542*, V562I, R1066H, I506V, I807M, which lead to a reduced CFTR function and thus, to more severe COVID-19. In conclusion, CFTR genetic analysis is an important tool in identifying patients at risk of severe COVID-19

Defining Kawasaki disease and pediatric inflammatory multisystem syndrome-temporally associated to SARS-CoV-2 infection during SARS-CoV-2 epidemic in Italy: results from a national, multicenter survey

Background: There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome-temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities. Methods: The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group - KDG) or KD-like (Kawacovid Group - KCG) disease between February 1st 2020, and May 31st 2020. Demographic, clinical, laboratory data, treatment information, and patients' outcome were collected in an online anonymized database (RedCAP®). Relationship between clinical presentation and SARS-CoV-2 infection was also taken into account. Moreover, clinical characteristics of KDG during SARS-CoV-2 epidemic (KDG-CoV2) were compared to Kawasaki Disease patients (KDG-Historical) seen in three different Italian tertiary pediatric hospitals (Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste; AOU Meyer, Florence; IRCCS Istituto Giannina Gaslini, Genoa) from January 1st 2000 to December 31st 2019. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groups. Results: One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis. 37,8% of patients among KCG presented hypotension/non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated ferritin and troponin-T characterized KCG. KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p = 0.04 and 71,9% vs 43,4%; p = 0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p < 0.0001). SARS-CoV-2 assay more often resulted positive in KCG than in KDG (75,5% vs 20%; p < 0.0001). Short-term follow data showed minor complications. Comparing KDG with a KD-Historical Italian cohort (598 patients), no statistical difference was found in terms of clinical manifestations and laboratory data. Conclusion: Our study suggests that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD and PIMS-TS. Older age at onset and clinical peculiarities like the occurrence of myocarditis characterize this multi-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

Probing effective field theory operators in the associated production of top quarks with a Z boson in multilepton final states at root s=13 TeV

Peer reviewe