FATTORI PREDITTIVI DI RISPOSTA VIROLOGICA SOSTENUTA IN PAZIENTI CON COINFEZIONE HIV-HCV TRATTATI CON PEG-INTERFERONE E RIBAVIRINA

Hepatitis C is a blood-borne infection caused by the hepatitis C virus (HCV). A chronic infection, which develops in most infected subjects, may lead to liver cirrhosis with ensuing liver dysfunction and liver cancer. About 30% of HIV-positive patients are coifected with HCV. The standard of care in HIV-HCV-coinfected subjects was a combination of pegylated interferon (peg-IFN)-alpha and ribavirin for 48 weeks until few months ago. The eradication of HCV was obtained in 20-55% of cases albeit with significant side effects. Further understanding of host factors that determine the effectiveness of treatment may provide diagnostic tools to distinguish patients who will be cured from those in whom treatment is likely to be futile. The aim of this thesis was to identify biomarkers and some conditions to predict outcome of combination therapy in HIV-HCV-infected patients. The parameters studied included microbial translocation markers as sCD14 and LPS, immune activation profile as CD8+CD38+, CD4+/CD8+ ratio, and in added a HAART intensification with CCR5 inhibitors, maraviroc. We showed that in HIV-HCV patients sCD14 correlates with the severity of liver disease and predicts early response to peg-IFN-apha/ribavirin. Moreover, during anti-HCV therapy there is a higher immune activation by CD8+CD38+ increasing. This data could be a major factor for outcome above all in the first phases of therapy. In conclusion, we evaluated that HAART intensification with maraviroc Per concludere si \ue8 valutato come l\u2019intensificazione della terapia HAART con maraviroc could increase T CD4+ recovery and translate in higher probability of sustained virological response in immunological non responder subjects

Optimisation of ITER Nb3Sn CICCs for coupling loss, transverse electromagnetic load and axial thermal contraction

The ITER cable-in-conduit conductors (CICCs) are built up from sub-cable bundles, wound in different stages, which are twisted to counter coupling loss caused by time-changing external magnet fields. The selection of the twist pitch lengths has major implications for the performance of the cable in the case of strain sensitive superconductors, i.e. Nb3Sn, as the electromagnetic and thermal contraction loads are large but also for the heat load from the AC coupling loss. Reduction of the transverse load and warm-up cool-down degradation can be reached by applying longer twist pitches in a particular sequence for the sub-stages, offering a large cable transverse stiffness, adequate axial flexibility and maximum allowed lateral strand support. Analysis of short sample (TF conductor) data reveals that increasing the twist pitch can lead to a gain of the effective axial compressive strain of more than 0.3 % with practically no degradation from bending. For reduction of the coupling loss, specific choices of the cabling twist sequence are needed with the aim to minimize the area of linked strands and bundles that are coupled and form loops with the applied changing magnetic field, instead of simply avoiding longer pitches. In addition we recommend increasing the wrap coverage of the CS conductor from 50 % to at least 70 %. The models predict significant improvement against strain sensitivity and substantial decrease of the AC coupling loss in Nb3Sn CICCs, but also for NbTi CICCs minimization of the coupling loss can be achieved. Although the success of long pitches to transverse load degradation was already demonstrated, the prediction of the combination with low coupling loss needs to be validated by a short sample test.Comment: to be published in Supercond Sci Techno

Proven intra and interobserver reliability in the echographic assessments of body fat changes related to HIV associated Adipose Redistribution Syndrome (HARS)

OBJECTIVE: To prove intra- and inter-observer's reliability of ultrasound (US) in the assessment of lipoatrophic findings related to the HIV associated Adipose Redistribution Syndrome (HARS). PATIENTS AND METHODS: In two separated sessions, 2 consecutive measurements of subcutaneous fat thickness (SFT) were performed by each observer at the deepest point of Bichat pad, the dorsal face of arm and the mid thigh for the assessment of facial, brachial and crural lipoatrophy, respectively. We enrolled 20 HIV patients, rotating an experienced and untrained sonologist. The assessments were performed avoiding any stand off pads in the skin and excluding artefacts due to the too abundant quantity of gel to obtaining, with minimal transducer pressure, the best resolution of the reference points. RESULTS: Means of facial, brachial and crural SFT showed no significant differences between the workers. Coefficients of variability (SD/mean x100) were similar for facial (ranges: 4.7-5.2% vs 4.9-5.6%, respectively), brachial (ranges: 5.8-8.4% vs 9.7-11.2%) and crural SFTs (ranges: 5.9-6% vs 6.2-8.7%). There was greater consistency in the measurements performed by the experienced vs the untrained worker. Inter-observer agreement, assessed through kappa statistic (k) analysis, confirmed increased measurement's agreement in the facial (k ranged from 0.40 to 0.60), brachial (k: 0.23-0.63) and crural SFT assessments (k: 0.58-0.70) from the 1(st) to 2(nd) session. CONCLUSIONS: US shows low intra observer variability and good inter observer reliability in the assessment of body fat changes related to the HARS. The different degree of consistency by the workers and the improvement of interobserver agreement, suggest to stating a well defined period of training to obtain better US reliabilit

Online coupling of pure O2 thermo-optical methods – 14C AMS for source apportionment of carbonaceous aerosols

This paper reports on novel separation methods developed for the direct determination of 14C in organic carbon (OC) and elemental carbon (EC), two sub-fractions of total carbon (TC) of atmospheric air particulate matter. Until recently, separation of OC and EC has been performed off-line by manual and time-consuming techniques that relied on the collection of massive CO2 fractions. We present here two on-line hyphenated techniques between a Sunset OC/EC analyzer and a MICADAS (MIni radioCArbon DAting System) accelerator mass spectrometer (AMS) equipped with a gas ion source. The first implementation facilitates the direct measurement in the low sample size range (<10 lg C) with high throughput on a routine basis, while the second explores the potential for a continuous-flow real-time CO2 gas feed into the ion source. The performance achieved with reference materials and real atmospheric samples will be discussed to draw conclusions on the improvement offered in the field of 14C aerosol source apportionment

TCV divertor upgrade for alternative magnetic configurations

The Swiss Plasma Center (SPC) is planning a divertor upgrade for the TCV tokamak. The upgrade aims at extending the research of conventional and alternative divertor configurations to operational scenarios and divertor regimes of greater relevance for a fusion reactor. The main elements of the upgrade are the installation of an in-vessel structure to form a divertor chamber of variable closure and enhanced diagnostic capabilities, an increase of the pumping capability of the divertor chamber and the addition of new divertor poloidal field coils. The project follows a staged approach and is carried out in parallel with an upgrade of the TCV heating system. First calculations using the EMC3-Eirene code indicate that realistic baffles together with the planned heating upgrade will allow for a significantly higher compression of neutral particles in the divertor, which is a prerequisite to test the power dissipation potential of various divertor configurations

The DEMO magnet system – Status and future challenges

We present the pre-concept design of the European DEMO Magnet System, which has successfully passed the DEMO plant-level gate review in 2020. The main design input parameters originate from the so-called DEMO 2018 baseline, which was produced using the PROCESS systems code. It defines a major and minor radius of 9.1 m and 2.9 m, respectively, an on-axis magnetic field of 5.3 T resulting in a peak field on the toroidal field (TF) conductor of 12.0 T. Four variants, all based on low-temperature superconductors (LTS), have been designed for the 16 TF coils. Two of these concepts were selected to be further pursued during the Concept Design Phase (CDP): the first having many similarities to the ITER TF coil concept and the second being the most innovative one, based on react-and-wind (RW) Nb3Sn technology and winding the coils in layers. Two variants for the five Central Solenoid (CS) modules have been investigated: an LTS-only concept resembling to the ITER CS and a hybrid configuration, in which the innermost layers are made of high-temperature superconductors (HTS), which allows either to increase the magnetic flux or to reduce the outer radius of the CS coil. Issues related to fatigue lifetime which emerged in mechanical analyses will be addressed further in the CDP. Both variants proposed for the six poloidal field coils present a lower level of risk for future development. All magnet and conductor design studies included thermal-hydraulic and mechanical analyses, and were accompanied by experimental tests on both LTS and HTS prototype samples (i.e. DC and AC measurements, stability tests, quench evolution etc.). In addition, magnet structures and auxiliary systems, e.g. cryogenics and feeders, were designed at pre-concept level. Important lessons learnt during this first phase of the project were fed into the planning of the CDP. Key aspects to be addressed concern the demonstration and validation of critical technologies (e.g. industrial manufacturing of RW Nb3Sn and HTS long conductors, insulation of penetrations and joints), as well as the detailed design of the overall Magnet System and mechanical structures

Neural stem cell transplantation in patients with progressive multiple sclerosis: an open-label, phase 1 study

Innovative pro-regenerative treatment strategies for progressive multiple sclerosis (PMS), combining neuroprotection and immunomodulation, represent an unmet need. Neural precursor cells (NPCs) transplanted in animal models of multiple sclerosis have shown preclinical efficacy by promoting neuroprotection and remyelination by releasing molecules sustaining trophic support and neural plasticity. Here we present the results of STEMS, a prospective, therapeutic exploratory, non-randomized, open-label, single-dose-finding phase 1 clinical trial (NCT03269071, EudraCT 2016-002020-86), performed at San Raffaele Hospital in Milan, Italy, evaluating the feasibility, safety and tolerability of intrathecally transplanted human fetal NPCs (hfNPCs) in 12 patients with PMS (with evidence of disease progression, Expanded Disability Status Scale &gt;= 6.5, age 18-55 years, disease duration 2-20 years, without any alternative approved therapy). The safety primary outcome was reached, with no severe adverse reactions related to hfNPCs at 2-year follow-up, clearly demonstrating that hfNPC therapy in PMS is feasible, safe and tolerable. Exploratory secondary analyses showed a lower rate of brain atrophy in patients receiving the highest dosage of hfNPCs and increased cerebrospinal fluid levels of anti-inflammatory and neuroprotective molecules. Although preliminary, these results support the rationale and value of future clinical studies with the highest dose of hfNPCs in a larger cohort of patients

Aerosols in the Pre-industrial Atmosphere

Purpose of Review: We assess the current understanding of the state and behaviour of aerosols under pre-industrial conditions and the importance for climate. Recent Findings: Studies show that the magnitude of anthropogenic aerosol radiative forcing over the industrial period calculated by climate models is strongly affected by the abundance and properties of aerosols in the pre-industrial atmosphere. The low concentration of aerosol particles under relatively pristine conditions means that global mean cloud albedo may have been twice as sensitive to changes in natural aerosol emissions under pre-industrial conditions compared to present-day conditions. Consequently, the discovery of new aerosol formation processes and revisions to aerosol emissions have large effects on simulated historical aerosol radiative forcing. Summary: We review what is known about the microphysical, chemical, and radiative properties of aerosols in the pre-industrial atmosphere and the processes that control them. Aerosol properties were controlled by a combination of natural emissions, modification of the natural emissions by human activities such as land-use change, and anthropogenic emissions from biofuel combustion and early industrial processes. Although aerosol concentrations were lower in the pre-industrial atmosphere than today, model simulations show that relatively high aerosol concentrations could have been maintained over continental regions due to biogenically controlled new particle formation and wildfires. Despite the importance of pre-industrial aerosols for historical climate change, the relevant processes and emissions are given relatively little consideration in climate models, and there have been very few attempts to evaluate them. Consequently, we have very low confidence in the ability of models to simulate the aerosol conditions that form the baseline for historical climate simulations. Nevertheless, it is clear that the 1850s should be regarded as an early industrial reference period, and the aerosol forcing calculated from this period is smaller than the forcing since 1750. Improvements in historical reconstructions of natural and early anthropogenic emissions, exploitation of new Earth system models, and a deeper understanding and evaluation of the controlling processes are key aspects to reducing uncertainties in future