52 research outputs found

    Analisi di settore: il corporate banking

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    Indice: Definizione del business - Analisi del macroambiente - Analisi della domanda - Analisi dell'offerta - Quadro competitiv

    Establishing temperate crustose early Holocene coralline algae as archives for palaeoenvironmental reconstructions of the shallow water habitats of the Mediterranean Sea

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    Over the past decades, coralline algae have increasingly been used as archives of palaeoclimate information due to their seasonal growth bands and their vast distribution from high latitudes to the tropics. Traditionally, these reconstructions have been performed mainly on high latitude species, limiting the geographical area of their potential use. Here we assess the use of temperate crustose fossil coralline algae from shallow water habitats for palaeoenvironmental reconstruction to generate records of past climate change. We determine the potential of three different species of coralline algae, Lithothamnion minervae, Lithophyllum stictaeforme and Mesophyllum philippii, with different growth patterns, as archives for pH (ÎŽ11B) and temperature (Mg/Ca) reconstruction in the Mediterranean Sea. Mg concentration is driven by temperature but modulated by growth rate, which is controlled by species‐specific and intraspecific growth patterns. L. minervae is a good temperature recorder, showing a moderate warming trend in specimens from 11.37 cal ka BP (from 14.2 ± 0.4°C to 14.9 ± 0.15°C) to today. In contrast to Mg, all genera showed consistent values of boron isotopes (ÎŽ11B) suggesting a common control on boron incorporation. The recorded ÎŽ11B in modern and fossil coralline specimens is in agreement with literature data about early Holocene pH, opening new perspectives of coralline‐based, high‐resolution pH reconstructions in deep time

    Radial access for percutaneous coronary procedure: relationship between operator expertise and complications

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    Objective The aim of this study was to investigate (1) whether the learning curve of new catheterization laboratory operators increases the incidence of complications of transradial access during percutaneous coronary interventions and (2) whether manual compression with a two-step approach is safe and efficient for radial access hemostasis. Methods We performed a prospective study with all consecutive patients who underwent a coronary diagnostic or intervention procedure with radial access. The primary end point was a composite of pulseless radial artery of the wrist and hematoma evaluated after 24 hours. The secondary end point of efficacy was defined as the presence of bleeding or hematoma after 30 seconds. Results From March 2016 to June 2016, 150 consecutive patients, of whom 147 underwent coronary angiography and/or percutaneous coronary intervention through radial access, were included in the present study. The primary end point was present in 33%, but pulseless radial artery of the wrist was present only in 5.3%. We found that the incidence of primary end point was statistically different according to the number of puncture attempts, with a cutoff of two punctures with blood. The secondary end point of safety was present only in 4.7% of the cases. Conclusion Radial access is feasible and safe even if performed by training physicians. Manual compression with early evaluation after 30 seconds is a safe technique for managing the radial access after sheath removal

    Transthyretin Protects against A-Beta Peptide Toxicity by Proteolytic Cleavage of the Peptide: A Mechanism Sensitive to the Kunitz Protease Inhibitor

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    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of amyloid ÎČ-peptide (A-Beta) in the brain. Transthyretin (TTR) is a tetrameric protein of about 55 kDa mainly produced in the liver and choroid plexus of the brain. The known physiological functions of TTR are the transport of thyroid hormone T4 and retinol, through binding to the retinol binding protein. TTR has also been established as a cryptic protease able to cleave ApoA-I in vitro. It has been described that TTR is involved in preventing A-Beta fibrilization, both by inhibiting and disrupting A-Beta fibrils, with consequent abrogation of toxicity. We further characterized the nature of the TTR/A-Beta interaction and found that TTR, both recombinant or isolated from human sera, was able to proteolytically process A-Beta, cleaving the peptide after aminoacid residues 1, 2, 3, 10, 13, 14,16, 19 and 27, as determined by mass spectrometry, and reversed phase chromatography followed by N-terminal sequencing. A-Beta peptides (1–14) and (15–42) showed lower amyloidogenic potential than the full length counterpart, as assessed by thioflavin binding assay and ultrastructural analysis by transmission electron microscopy. A-Beta cleavage by TTR was inhibited in the presence of an αAPP peptide containing the Kunitz Protease Inhibitor (KPI) domain but not in the presence of the secreted αAPP derived from the APP isoform 695 without the KPI domain. TTR was also able to degrade aggregated forms of A-Beta peptide. Our results confirmed TTR as a protective molecule in AD, and prompted A-Beta proteolysis by TTR as a protective mechanism in this disease. TTR may prove to be a useful therapeutic agent for preventing or retarding the cerebral amyloid plaque formation implicated in AD pathology

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

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    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

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    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

    COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

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    Background and objectives: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. Methods: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score > 3 or at least 1 comorbidity, lower risk: EDSS score ≀ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). Results: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p < 0.001), RR = 2.19 for ICU admission (p < 0.001), and RR = 2.43 for death (p < 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). Discussion: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon

    SARS-CoV-2 serology after COVID-19 in multiple sclerosis: An international cohort study

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    DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

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    We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

    “[
] Is it right to force Swedish children to go to school with the ghetto children? [
]” - written by a Flashback member : A qualitative study on how school segregation and school selection can be constructed on Flashback forum

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    Syftet med studien Ă€r att undersöka hur nĂ„gra röster pĂ„ Flashback forum problematiserar mĂ„ngkulturalitet i segregerade skolor i förhĂ„llande till skolval. Tidigare forskning visar att förĂ€ldrar med svensk bakgrund undviker mĂ„ngkulturella och stigmatiserade bostadsomrĂ„den, nĂ€r det kommer till val av skola för deras barn. Detta till följd av den negativa uppfattning förĂ€ldrarna har om invandrarbarn. Studien genomfördes utifrĂ„n en kvalitativ forskningsstrategi med hjĂ€lp av mĂ„lstyrt urval. Forskningsdeltagarna bestod av Flashbackmedlemmar som uttryckte sig kritiskt mot mĂ„ngkulturella skolor och invandrarbarn. Studiens empiriska material hĂ€mtades frĂ„n olika trĂ„dar pĂ„ det digitala diskussionsforumet Flashback forum. För att tolka studiens resultat anvĂ€ndes teorier om stigma och figurationen etablerade-outsiders. Resultatet presenteras genom kvalitativ innehĂ„llsanalys som tillvĂ€gagĂ„ngssĂ€tt, dĂ€r Flashback inlĂ€ggen har analyserats utifrĂ„n ett manifest och latent förhĂ„llningssĂ€tt. Slutsatser som antagits Ă€r att Flashbackmedlemmar uttrycker en oro över att ha deras barn i en etnisk blandad skola med för mĂ„nga invandrarbarn. Detta med anledningen att de anser att invandrarbarn utgör ett hot mot de svenska barnens psykiska samt fysiska hĂ€lsa och skolgĂ„ng, dĂ€r frĂ€mst barn frĂ„n ett icke-europeiskt ursprung pekas ut som de farliga eller kriminella.The purpose of the study was to investigate how some voices on Flashback forum problematise multiculturalism in segregated schools in relation to school selection. Previous research indicates that parents from Swedish background avoid multicultural and stigmatized residential areas, when it comes to school selection for their children. This being a result of the negative perception parents have of immigrant children. The study was conducted based on a qualitative research strategy with the help of a goal-oriented selection. The research participants consisted of Flashback members who were selected for being critical of multicultural schools and immigrant children. This study’s empirical material was taken from various thread on the digital discussion forum, Flashback forum.This study’s results were interpreted through the theories of stigma and the figuration of established-outsiders. The results are presented through qualitive content analysis, where the Flashback members posts have been analysed through a manifest and latent approach. The conclusions drawn were that the Flashback members have expressed concern about having their children in an ethnically mixed school with too many immigrant children. This is because they believe that immigrant children pose a threat to Swedish children's mental and physical health as well as their education. Where children of non-European origin are primarily singled out as dangerous or criminal
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