Consenso e dissenso in tempo di emergenza

Abstract: First of all, this essay intends to thematize the relationship between dissent, pluralism and democracy, at the time of the primacy of technicians (now more conservative, now liberal ones) and of the government of emergencies (whether real or emphasized). Further on, we are going to ponder on the role played by the new media in shaping the public opinion and the political participation, then on the challenges and contradictions that cross contemporary postindustrial societies characterized by the IT and technological revolution. In closing, we will bear a theoretical and political stance of ours: a return to “a new humanism”, whose outline will be explained in the last paragraph of this work.RiassuntoQuesto saggio intende, innanzitutto, tematizzare il rapporto tra dissenso, pluralismo e democrazia, al tempo del primato dei tecnici (ora più conservatore, ora liberal) e del governo delle emergenze (reali o enfatizzate che siano). Si proseguirà riflettendo prima sull’incidenza della macchina multimediale nei processi di formazione dell’opinione pubblica e di partecipazione politica, poi sulle sfide e le contraddizioni che attraversano le società postindustriali contrassegnate dalla rivoluzione informatica e tecnologica. In chiusura, una personale presa di posizione teorica e politica: quel ritorno a “un nuovo umanesimo”, di cui si spiegheranno i contorni nell’ultimo paragrafo del lavoro

LEOPARDI POLITICO TRA AMOR PATRIO E FRATELLANZA UNIVERSALE

Mai come durante le settimane di dolore e preoccupazione legateall'emergenza Coronavirus si sono manifestati così tanti atteggiamentidi fierezza nazionale: un sussulto di orgoglio generato da un concorsodrammatico di circostanze che è diventato quasi un moto spontaneo eliberatorio utile ad esorcizzare le paure e le tensioni accumulate.Il senso di comunità inevitabilmente si rafforza soprattutto neimomenti di smarrimento collettivo, quando si cerca un 'noi' che ciprotegga e rassicuri. Va compresa dunque questa forma di patriottismoche nasce dall'angoscia e dal desiderio di non sentirsi soli in frangentitanto difficili.Certo, tutt

An improved substructuring approach for dynamic modelling – The example of the ITER vacuum vessel

Abstract This study deals with the substructuring method that is adopted for treating complex structures, such as the ITER Tokamak, as an assembly of different components or substructures. This method uses basic mass and stiffness matrices combined with conditions representative of the geometrical compatibility along the substructure boundaries. This approach makes it possible to simulate the dynamic behaviour of the (complex) ITER Vacuum Vessel (VV), subjected to dynamic loading (e.g. seismic), by means of a simplified model (finite element discretization) with little loss of accuracy. In this framework, a simplified model of the ITER VV for use in global seismic analyses has been developed and implemented. In order to minimize the wavefront (and hence computational time), the simplified model is made of multiple superelements, each representing a part of the VV. Moreover, in order to reduce the number of Degrees of Freedom (DoFs) needed along the boundaries of the different substructures, a new approach has also been developed for the breakdown of the benchmark model

Optimal social distancing in epidemic control: cost prioritization, adherence and insights into preparedness principles

The COVID-19 pandemic experience has highlighted the importance of developing general control principles to inform future pandemic preparedness based on the tension between the different control options, ranging from elimination to mitigation, and related costs. Similarly, during the COVID-19 pandemic, social distancing has been confirmed to be the critical response tool until vaccines become available. Open-loop optimal control of a transmission model for COVID-19 in one of its most aggressive outbreaks is used to identify the best social distancing policies aimed at balancing the direct epidemiological costs of a threatening epidemic with its indirect (i.e., societal level) costs arising from enduring control measures. In particular, we analyse how optimal social distancing varies according to three key policy factors, namely, the degree of prioritization of indirect costs, the adherence to control measures, and the timeliness of intervention. As the prioritization of indirect costs increases, (i) the corresponding optimal distancing policy suddenly switches from elimination to suppression and, finally, to mitigation; (ii) the "effective" mitigation region-where hospitals' overwhelming is prevented-is dramatically narrow and shows multiple control waves; and (iii) a delicate balance emerges, whereby low adherence and lack of timeliness inevitably force ineffective mitigation as the only accessible policy option. The present results show the importance of open-loop optimal control, which is traditionally absent in public health preparedness, for studying the suppression-mitigation trade-off and supplying robust preparedness guidelines

Field clinical study evaluating the efficacy and safety of an oral formulation containing milbemycin oxime/praziquantel (Milbemax®, Novartis Animal Health) in the chemoprevention of the zoonotic canine infection by Dirofilaria repens

Dirofilaria repens is the causative agent of subcutaneous dirofilariosis of dogs, other animals and humans. This nematode is transmitted by mosquitoes of Aedes, Anopheles and Culex genera. In dogs, the parasite may cause subclinical infection or cutaneous signs. Recently, D. repens has emerged and spread in different geographical areas, with an increase of cases in dogs and humans. Chemoprevention in dogs in endemic areas is the most reliable approach for controlling this infection. This paper describes a randomized, blocked and multicentric clinical field study investigating the efficacy of an oral, chewable formulation containing milbemycin oxime/praziquantel (Milbemax®, Novartis Animal Health) in the chemoprevention of subcutaneous dirofilariosis in dogs. METHODS: This study was conducted in endemic areas of Italy. A total of 249 dogs, at two sites, negative for D. repens, were allocated into two groups (i.e. Treated -T1 vs Untreated-T2) with a ratio of 1:1, and subjected to clinical visits and blood sampling once monthly until the end of the study. All blood samples were microscopically and genetically examined. Animals belonging to T1 group received a minimum target dose of 0.5 mg/kg bodyweight of milbemycin oxime and 5 mg/kg of praziquantel in commercial tablets (Milbemax®) according body weight once every 4 weeks. Animals of group T2 were not treated with Milbemax® but received, when necessary, specific parasiticide treatments. The study duration was 336 ± 2 days for each dog. RESULTS: A total of 219 dogs completed the study (i.e. 111 in T1 and 108 in T2), while 30 dogs (i.e. 13 in T1, 17 in T2) were withdrawn for a variety of reasons unrelated to administration of Milbemax®. The percentages of animals not showing microfilariae of D. repens were 100% (111 animals) in T1 and 94.7% (108 animals out of 114) in group T2. Milbemax® was shown to be safe in treated dogs. CONCLUSIONS: The results of this study confirm that the monthly use of Milbemax® in dogs is effective and safe for the prevention of subcutaneous dirofilariosis in endemic areas

NUP85 as a Neurodevelopmental Gene: From Podocyte to Neuron

Pathogenic gene variants encoding nuclear pore complex (NPC) proteins were previously implicated in the pathogenesis of steroid-resistant nephrotic syndrome (SRNS). The NUP85 gene, encoding nucleoporin, is related to a very rare form of SRNS with limited genotype-phenotype information. We identified an Italian boy affected with an SRNS associated with severe neurodevelopmental impairment characterized by microcephaly, axial hypotonia, lack of achievement of motor milestones, and refractory seizures with an associated hypsarrhythmic pattern on electroencephalography. Brain magnetic resonance imaging (MRI) showed hypoplasia of the corpus callosum and a simplified gyration of the cerebral cortex. Since the age of 3 years, the boy was followed up at our Pediatric Nephrology Department for an SRNS, with a focal segmental glomerulosclerosis at renal biopsy. The boy died 32 months after SRNS onset, and a Whole-Exome Sequencing analysis revealed a novel compound heterozygous variant in NUP85 (NM_024844.5): 611T>A (p.Val204Glu), c.1904T>G (p.Leu635Arg), inherited from the father and mother, respectively. We delineated the clinical phenotypes of NUP85-related disorders, reviewed the affected individuals so far reported in the literature, and overall expanded both the phenotypic and the molecular spectrum associated with this ultra-rare genetic condition. Our study suggests a potential occurrence of severe neurological phenotypes as part of the NUP85-related clinical spectrum and highlights an important involvement of nucleoporin in brain developmental processes and neurological function

Diagnosis, treatment, and follow-up of a case of Wolman disease with hemophagocytic lymphohistiocytosis

: Wolman Disease (WD) is a severe multi-system metabolic disease due to lysosomal acid lipase (LAL) deficiency. We report on a WD infant who developed an unusual hemophagocytic lymphohistiocytosis (HLH) phenotype related to WD treated with sebelipase alfa. A male baby came to our attention at six months of life for respiratory insufficiency and sepsis, abdominal distension, severe hepatosplenomegaly, diarrhea, and severe growth retardation. HLH was diagnosed and treated with intravenous immunoglobulin, steroids, cyclosporine, broad-spectrum antimicrobial therapy, and finally with the anti-IL-6 drug tocilizumab. WD was suspected for the presence of adrenal calcifications and it was confirmed by LAL enzyme activity and by molecular analysis of LIPA. Plasma oxysterols cholestan-3β,5α,6β-triol (C-triol), and 7-ketocholesterol (7-KC) were markedly increased. Sebelipase alfa was started with progressive amelioration of biochemical and clinical features. The child died from sepsis, 2 months after sebelipase discontinuation requested by parents. Our case shows the importance of an early diagnosis of WD and confirms the difficulty to reach a diagnosis in the HLH phenotype. Sebelipase alpha is an effective treatment for LAL deficiency, also in children affected by WD. Further data are necessary to confirm the utility of measuring plasma c-triol as a biochemical marker of the disease

Insights into the Sesquiterpenoid Pathway by Metabolic Profiling and De novo Transcriptome Assembly of Stem-Chicory (Cichorium intybus Cultigroup "Catalogna")

Stem-chicory of the "Catalogna" group is a vegetable consumed for bitter-flavored stems. Type and levels of bitter sesquiterpene lactones (STLs) participate in conferring bitterness in vegetables. The content of lactucin-and lactucopocrin-like STLs was higher in "Molfettese" than "Galatina" landrace stalks, regardless of the cultivation sites, consistently with bitterness scores and gustative differences. The "Galatina" transcriptome assembly resulted in 58,872 unigenes, 77% of which were annotated, paving the way to molecular investigation of the STL pathway. Comparative transcriptome analysis allowed the identification of 69,352 SNPs and of 1640 differentially expressed genes that maintained the pattern independently of the site. Enrichment analyses revealed that 4 out of 29 unigenes were up-regulated in "Molfettese" vs "Galatina" within the sesquiterpenoid pathway. The expression of two germacrene A -synthase (GAS) and one -oxidase (GAO) genes of the costunolide branch correlated positively with the contents of lactucin-like molecules, supporting that STL biosynthesis regulation occurs at the transcriptional level. Finally, 46 genes encoding transcription factors (TFs) maintained a differential expression pattern between the two varieties regardless of the growth site; correlation analyses among TFs, GAS, GAO gene expressions and STLs contents suggest that one MYB and one bHLH may act in the pathway

Postmastectomy radiotherapy for locally advanced breast cancer receiving neoadjuvant chemotherapy.

Neoadjuvant chemotherapy (NAC) is widely used in locally advanced breast cancer (BC) treatment. The role of postmastectomy radiotherapy (PMRT) after NAC is strongly debated. The aim of our analysis was to identify major prognostic factors in a single-center series, with emphasis on PMRT. From 1997 to 2011, 170 patients were treated with NAC and mastectomy at our center; 98 cases (57.6%) underwent PMRT and 72 cases (42.4%) did not receive radiation. At a median follow-up period of 7.7 years (range 2–16) for the whole cohort, median time to locoregional recurrence (LRR) was 3.3 years (range 0.7–12.4). The 5-year and 10-year actuarial LRR rate were 14.5% and 15.9%, respectively. At the multivariate analysis the factors that significantly correlated with survival outcome were ≥4 positive nodes (HR 5.0, 1.51–16.52; P=0.035), extracapsular extension (HR 2.18, 1.37–3.46; P=0.009), and estrogen receptor positive disease (HR 0.57, 0.36–0.90; P=0.003). Concerning LRR according to use of radiation, PMRT reduced LRR for patient with clinical T3 staged disease (P=0.015). Our experience confirmed the impact of pathological nodal involvement on survival outcome. PMRT was found to improve local control in patients presenting with clinical T3 tumors, regardless of the response to chemotherapy

Metabolomics application for the design of an optimal diet

Precision nutrition is an emerging branch of nutrition science that aims to use modern omics technologies (genomics, proteomics, and metabolomics) to assess an individual’s response to specific foods or dietary patterns and thereby determine the most effective diet or lifestyle interventions to prevent or treat specific diseases. Metabolomics is vital to nearly every aspect of precision nutrition. It can be targeted or untargeted, and it has many applications. Indeed, it can be used to comprehensively characterize the thousands of chemicals in foods, identify food by-products in human biofluids or tissues, characterize nutrient deficiencies or excesses, monitor biochemical responses to dietary interventions, track long- or short-term dietary habits, and guide the development of nutritional therapies. Indeed, metabolomics can be coupled with genomics and proteomics to study and advance the field of precision nutrition. Integrating omics with epidemiological and clinical data will begin to define the beneficial effects of human food metabolites. In this review, we present the metabolome and its relationship to precision nutrition. Moreover, we describe the different techniques used in metabolomics and present how metabolomics has been applied to advance the field of precision nutrition by providing notable examples and cases