BURDEN OF PROOF, STANDARD OF PROOF, AND EVIDENCE ISSUES UNDER THE CISG

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Two-step growth mechanism of supported Co3O4-based sea-urchin like hierarchical nanostructures

The formation mechanism of Co3O4-based sea-urchin like nanostructures from Co-O-B layers is unveiled. In this process, promoted by oxidizing annealing, B plays a major role, inducing first a chemical reduction of Co and the formation of a metallic particle core. The growth of nano-needles from the particle surface occurs through outdiffusion and oxidation of Co from the metallic reservoir

Molecular and cellular correlates of the CIITA-mediated inhibition of HTLV-2 Tax-2 transactivator function resulting in loss of viral replication

<p>Abstract</p> <p>Background</p> <p>MHC class II transactivator CIITA inhibits the function of HTLV-2 Tax-2 viral transactivator and, consequently, the replication of the virus in infected cells. Moreover overexpression of the nuclear factor NF-YB, that cooperates with CIITA for the expression of MHC class II genes, results also in inhibition of Tax-2 transactivation. The purpose of this investigation was to assess the cellular and molecular basis of the CIITA-mediated inhibition on Tax-2, and the relative role of NF-YB in this phenomenon.</p> <p>Methods</p> <p>By co-immunoprecipitation of lysates from 293T cells cotransfected with CIITA or fragments of it, and Tax-2 it was assessed whether the two factors interact <it>in vivo</it>. A similar approach was used to assess Tax-2-NF-YB interaction. In parallel, deletion fragments of CIITA were tested for the inhibition of Tax-2-dependent HTLV-2 LTR-luciferase transactivation. Subcellular localization of CIITA and Tax-2 was investigated by immunofluorescence and confocal microscopy.</p> <p>Results</p> <p>CIITA and Tax-2 interact <it>in vivo </it>through at least two independent regions, at the 1-252 N-term and at the 410-1130 C-term, respectively. Interestingly only the 1-252 N-term region mediates Tax-2 functional inhibition. CIITA and Tax-2 are localized both in the cytoplasm and in the nucleus, when separately expressed. Instead, when coexpressed, most of Tax-2 colocalize with CIITA in cytoplasm and around the nuclear membrane. The Tax-2 minor remaining nuclear portion also co-localizes with CIITA. Interestingly, when CIITA nucleus-cytoplasm shuttling is blocked by leptomycin B treatment, most of the Tax-2 molecules are also blocked and co-localize with CIITA in the nucleus, suggesting that CIITA-Tax-2 binding does not preclude Tax-2 entry into the nucleus.</p> <p>Finally, the nuclear factor NF-YB, also strongly binds to Tax-2. Notably, although endogenous NF-YB does not inhibit Tax-2-dependent HTLV-2 LTR transactivation, it still binds to Tax-2, and in presence of CIITA, this binding seems to increase.</p> <p>Conclusions</p> <p>These results strongly suggest that CIITA inhibit Tax-2 by binding the viral transactivator both directly or through a tripartite interaction with NF-YB in. CIITA is therefore a viral restriction factor for HTLV-2 and this open the possibility to control HTLV-2 viral replication and spreading by the controlled induction of CIITA in infected cells</p

Impact of deep convection in the tropical tropopause layer in West Africa: in-situ observations and mesoscale modelling

We present the analysis of the impact of convection on the composition of the tropical tropopause layer region (TTL) in West-Africa during the AMMA-SCOUT campaign. Geophysica M55 aircraft observations of water vapor, ozone, aerosol and CO2 show perturbed values at altitudes ranging from 14 km to 17 km (above the main convective outflow) and satellite data indicates that air detrainment is likely originated from convective cloud east of the flight. Simulations of the BOLAM mesoscale model, nudged with infrared radiance temperatures, are used to estimate the convective impact in the upper troposphere and to assess the fraction of air processed by convection. The analysis shows that BOLAM correctly reproduces the location and the vertical structure of convective outflow. Model-aided analysis indicates that in the outflow of a large convective system, deep convection can largely modify chemical composition and aerosol distribution up to the tropical tropopause. Model analysis also shows that, on average, deep convection occurring in the entire Sahelian transect (up to 2000 km E of the measurement area) has a non negligible role in determining TTL composition

Towards the Development of a Z-Scheme FeOx/g-C3N4 Thin Film and Perspectives for Ciprofloxacin Visible Light-Driven Photocatalytic Degradation

Thermally synthesized graphitic carbon nitride (g-C3N4) over pulsed laser deposition (PLD) produced urchin-like iron oxide (FeOx) thin films were fabricated via in situ and ex situ processes. Materials characterisation revealed the formation of the graphitic allotrope of C3N4 and a bandgap Eg for the combined FeOx/g-C3N4 of 1.87 and 1.95 eV for each of the different fabrication strategies. The in situ method permitted to develop a novel petal-like morphology, whereas for the ex situ method, a morphological mixture between FeOx bulk and g-C3N4 was observed. Given the improved optical and morphological properties of the in situ film, it was employed as a proof of concept for the direct photocatalysis and photo-Fenton removal of ciprofloxacin antibiotic (CIP) under visible light irradiation. Improved photocatalytic activity (rate constant k = 8.28 × 10−4 min−1) was observed, with further enhancement under photo-Fenton conditions (k = 2.6 × 10−3 min−1), in comparison with FeOx + H2O2 (k = 1.6 × 10−3 min−1) and H2O2 only (k = 1.3 × 10−4 min−1). These effects demonstrate the in situ methodology as a viable route to obtain working heterojunctions for solar photocatalysis in thin-film materials, rather than the more common powder materials

Monitoraggio della Sicurezza Energetica Italiana ed Europea

Rassegna trimestrale di monitoraggio su Sicurezza Energetica per l'Osservatorio di Politica Internazionale di Ministero degli Affari Esteri, Senato della Repubblica e Camera dei Deputati

In Stent Restenosis Predictors after Carotid Artery Stenting

Purpose. The long-term efficacy of carotid artery stenting is debated. Predictors of stent restenosis are not fully investigated. Our aim was to assess the incidence of long term restenosis after CAS and to identify some predictors of restenosis. Methods. We retrospectively selected 189 treated patients and we obtained the survival Kaplan-Meier curves for overall survival, for freedom from stroke or death and from restenosis. To correlate clinical, radiological, and procedural variables to stent restenosis, an univariate analysis was performed while to determine independent predictors of restenosis, a multivariate analysis was applied. Results. At 1, 3, and 5 years, the cumulative overall survival rate was 98%, 94%, and 92% with a cumulative primary patency rate of 87%, 82.5%, and 82.5%. The percentage residual stenosis after CAS and multiple stents deployment were independent predictors of restenosis, while diabetes and tumors are suggestive but not significant predictors of restenosis. Conclusions. In our CAS experience, encouraging long-term results seem to derive from both neurological event free rate and restenosis incidence. Adequate recanalization of the treated vessel is important to limit the development of stent restenosis. Multiple stents deployment, and with less evidence, diabetes, or neoplasms has to be considered to facilitate restenosis

The Differential Diagnosis of Discrepant Thyroid Function Tests: Insistent Pitfalls and Updated Flow-Chart Based on a Long-Standing Experience.

Background: Discrepant thyroid function tests (TFTs) are typical of inappropriate secretion of TSH (IST), a rare entity encompassing TSH-secreting adenomas (TSHoma) and Resistance to Thyroid Hormone (RTHβ) due to THRB mutations. The differential diagnosis remains a clinical challenge in most of the cases. The objective of this study was to share our experience with patients presenting with discrepant TFTs outlining the main pitfalls in the differential diagnosis. Methods: medical records of 100 subjects with discrepant TFTs referred to Thyroid Endocrine Centers at the University of Milan were analyzed, retrospectively. Patients were studied by dynamic testing (TRH test, T3-suppression test, or a short course of long-acting somatostatin analog, when appropriate), THRB sequencing, and pituitary imaging. Results: 88 patients were correctly diagnosed as RTHβ with (n = 59; 16 men, 43 women) or without THRB variants (n = 6; 2 men, 4 female) or TSHoma (n = 23; 9 men, 14 women). We identified 14 representative subjects with an atypical presentation or who were misdiagnosed. Seven patients, with spurious hyperthyroxinemia due to assays interference were erroneously classified as RTHβ (n = 4) or TSHoma (n = 3). Three patients with genuine TSHomas were classified as laboratory artifact (n = 2) or RTHβ (n = 1). Two TSHomas presented atypically due to coexistent primary thyroid diseases. In one RTHβ a drug-induced thyroid dysfunction was primarily assumed. These patients experienced a mean diagnostic delay of 26 ± 14 months. Analysis of the investigations which can differentiate between TSHoma and RTHβ showed highest accuracy for the T3-suppression test (100% specificity with a cut-off of TSH <0.11 μUI/ml). Pituitary MRI was negative in 6/26 TSHomas, while 11/45 RTHβ patients had small pituitary lesions, leading to unnecessary surgery in one case. Conclusions: Diagnostic delay and inappropriate treatments still occur in too many cases with discrepant TFTs suggestive of central hyperthyroidism. The insistent pitfalls lead to a significant waste of resources. We propose a revised flow-chart for the differential diagnosis

Current models of care for the management of HIV patients with comorbidities in England: a survey

Introduction: The number of people aged ]50 living with HIV in the UK is rapidly increasing. Effective treatment means HIV is usually well controlled; however, there has been an increase in individuals experiencing comorbid conditions associated with ‘‘normal’’ ageing. This aim of this study was to find out what models of care are currently in place for the management of patients with comorbidities. Materials and methods: A link to an online questionnaire was sent via the British HIV Association (BHIVA) Audit Committee to one HIV clinician in each HIV unit in England. Results: Forty-four units responded. Only 11 units (25%) provided specialized clinics for the management of comorbidities. These included: 1) Specialist clinics for the management of a non-infectious comorbidity (any age) e.g. a liver or renal clinic (n10). These clinics utilized in-person appointments (n3), or a combination of virtual and in-person appointments (n7). They were managed by an HIV clinician and non-HIV clinician together (n8), HIV clinician with an interest in the specialist area (n4) or specialist with an interest in HIV (n4). 2) Services for HIV patients with multiple comorbidities (any age) (n2). 3) Dedicated clinics for older people (n5) with eligibility determined by age (]50 years) or the presence of a comorbidity. Additionally, two HIV units employed a GP on site and two had set up a locally enhanced service providing enhanced primary care for HIV-positive patients. Six HIV units ran nurse-led clinics for patients with comorbid conditions. Co-ordination of care for patients with comorbid conditions was conducted by an HIV specialist doctor (n27), the patient’s GP (n18), HIV specialist nurse (n11) or the patient themselves (n9). Eleven clinics reported using case management for patients with multiple comorbid conditions. Self-management support (e.g. nurse-led or as part of an expert patient programme) for patients with comorbid conditions was provided at 18 HIV units. Conclusions: Only a quarter of the clinics surveyed had set up clinics for the management of comorbidities in people living with HIV. While a variety of different approaches were used, services were usually focused on the management of one comorbidity, and few provided services for multiple comorbidities. This is an increasing priority in the context of an ageing population. P162 Th