GEN-O-MA project: an Italian network studying clinical course and pathogenic pathways of moyamoya disease—study protocol and preliminary results

Background: GENetics of mOyaMoyA (GEN-O-MA) project is a multicenter observational study implemented in Italy aimed at creating a network of centers involved in moyamoya angiopathy (MA) care and research and at collecting a large series and bio-repository of MA patients, finally aimed at describing the disease phenotype and clinical course as well as at identifying biological or cellular markers for disease progression. The present paper resumes the most important study methodological issues and preliminary results. Methods: Nineteen centers are participating to the study. Patients with both bilateral and unilateral radiologically defined MA are included in the study. For each patient, detailed demographic and clinical as well as neuroimaging data are being collected. When available, biological samples (blood, DNA, CSF, middle cerebral artery samples) are being also collected for biological and cellular studies. Results: Ninety-eight patients (age of onset mean ± SD 35.5 ± 19.6 years; 68.4% females) have been collected so far. 65.3% of patients presented ischemic (50%) and haemorrhagic (15.3%) stroke. A higher female predominance concomitantly with a similar age of onset and clinical features to what was reported in previous studies on Western patients has been confirmed. Conclusion: An accurate and detailed clinical and neuroimaging classification represents the best strategy to provide the characterization of the disease phenotype and clinical course. The collection of a large number of biological samples will permit the identification of biological markers and genetic factors associated with the disease susceptibility in Italy

Quasistatic delamination of sandwich-like Kirchhoff-Love plates

A quasistatic rate-independent adhesive delamination problem of laminated plates with a finite thickness is considered. By letting the thickness of the plates go to zero, a rate-independent delamination model for a laminated Kirchhoff-Love plate is obtained as limit of these quasistatic processes. The same dimension reduction procedure is eventually applied to processes which are sensitive to delamination modes, namely opening vs. shearing is distinguishe

Shoe manufacturing wastes: Characterisation of properties and recovery options

Using the renowned shoe manufacturing sector in Marche Region (Italy) as a case-study, this paper deals with the characterisation of (1) the chemical and physical properties of representative types of shoe manufacturing wastes, (2) the quality profile of a particular material recovery finalised to a soil destination, and (3) the flue gas emissions from burning tests in view of the potential for energy recovery. The property characterisation has primarily revealed the following aspects: a general condition of resulting higher ash contents in shoe waste materials having a mineral or synthetic processing origin; and relatively high energy contents, ranging on the whole expressed as LHV (lower heating value) from 15,710 kJ kg-1 (for vegetable-tanned leather dust) to 42,439 kJ kg-1 (for natural rubber). The characterisation of a fertiliser that can be generated from the particular waste type of vegetable-tanned leather dust has determined an interesting quality profile classifiable as organic-nitrogen fertiliser with acceptable values of the humification parameters and heavy metal contents significantly below the assumed quality limits. Finally, simplified pilot-scale burning tests have provided the following findings: higher NOx emissions produced from leather-based materials as compared with the cellulose-based material, which are likely attributable to the substantial “fuel nitrogen” content of the original animal skins; higher HCl emissions produced from the leather-based materials in comparison with the cellulose-based material; and a more even combustion process occurred for the leather dust than for the other shoe materials

Characterization of Silicon Photomultipliers after proton irradiation up to 101410^{14} neq/cm2n_{eq}/cm^{2}

Silicon photomultipliers (SiPMs) are highly-sensitive photodetectors emerging as the technology of choice for many applications, including large high-energy physics experiments where they often are exposed to high radiation fluences. In recent years, there has been an increasing interest in assessing the performance deterioration of such detectors after the irradiation with proton or neutron, with different fluence levels. In this work, samples of different FBK SiPM technologies, made with different manufacturing technologies, were irradiated at the INFN-LNS facility (Italy) with protons reaching fluences up to about 10^14 neq/cm^2 (1 MeV neutron equivalent) and their performances were characterized in detail after about 30-days room temperature annealing. The results show a significant worsening of the primary noise (dark count rate) of the detectors, which increases with the irradiation fluence, whereas the other performance parameters like the micro-cell gain, the correlated noise probability and the photon detection efficiency do not show significant variations up to 10^11 neq/cm^2 at least. The breakdown voltage estimation after irradiation is another important aspect for a SiPM. In this contribution, we show several methods for its estimation and compare the results. We also introduced new methodologies to characterize the performance of the SiPMs when they present a very high level of noise, such as the estimation of the dark count rate based on the measured reverse current, the estimation of variations in the photon detection efficiency through the measurement of the responsivity, and the measurement of the correlated noise and the gain through the average charge in response to a pulsed light signal. Lastly, we also analyzed the spatial localization of the proton-induced defects inside the device, i.e. the defects that mostly contribute to the increase of the DCR of the device, through the emission microscopy (EMMI) technique. In particular, we analyzed the SiPMs at the single cell level, trying to identify and spatially localize the defects

Towards the Personalized Treatment of Glioblastoma: Integrating Patient-Specific Clinical Data in a Continuous Mechanical Model.

Glioblastoma multiforme (GBM) is the most aggressive and malignant among brain tumors. In addition to uncontrolled proliferation and genetic instability, GBM is characterized by a diffuse infiltration, developing long protrusions that penetrate deeply along the fibers of the white matter. These features, combined with the underestimation of the invading GBM area by available imaging techniques, make a definitive treatment of GBM particularly difficult. A multidisciplinary approach combining mathematical, clinical and radiological data has the potential to foster our understanding of GBM evolution in every single patient throughout his/her oncological history, in order to target therapeutic weapons in a patient-specific manner. In this work, we propose a continuous mechanical model and we perform numerical simulations of GBM invasion combining the main mechano-biological characteristics of GBM with the micro-structural information extracted from radiological images, i.e. by elaborating patient-specific Diffusion Tensor Imaging (DTI) data. The numerical simulations highlight the influence of the different biological parameters on tumor progression and they demonstrate the fundamental importance of including anisotropic and heterogeneous patient-specific DTI data in order to obtain a more accurate prediction of GBM evolution. The results of the proposed mathematical model have the potential to provide a relevant benefit for clinicians involved in the treatment of this particularly aggressive disease and, more importantly, they might drive progress towards improving tumor control and patient's prognosis

Sensitivity analysis of the parameters S_n and δ_n.

<p>The influence of the parameters <i>S</i>_<i>n</i> and <i>δ</i>_<i>n</i> on the cell volume fraction and on the dimensionless nutrient concentration is reported at time <i>t</i> = 9 days.</p

Influence of brain fibers’ alignment on tumor growth.

<p>(A) Tumor concentration plotted over the <i>T</i>_<i>xx</i> component (in transparency), at times <i>t</i> = 5 day, <i>t</i> = 15 day, <i>t</i> = 25 day: the cellular fraction shows an anisotropic distribution that follows the preferential direction determined by the <i>T</i>_<i>xx</i> component. (B) Tumor volume at <i>t</i> = 25 day overlapped to the maps of <i>T</i>_<i>xx</i> over the brain mesh cut along <i>xy</i> and <i>xz</i> planes and to the map of <i>T</i>_<i>zz</i> over the brain mesh cut along <i>xz</i>-plane: the glioblastoma assumes an elongated shape along the <i>x</i> direction, whereas it has a flat top in the <i>z</i>-direction, as <i>T</i>_<i>zz</i> is almost null there.</p

Sensitivity analysis of the parameters k_n and M.

<p>The influence of the parameters <i>k</i>_<i>n</i> and <i>M</i> on the cells volume fraction distribution at time <i>t</i> = 6 days is studied. The resulting tumor are characterized in terms of: the ratio between the maximum volume fraction at the final time, <i>ϕ</i>^<i>M</i>, and maximum initial volume fraction, </p><p></p><p></p><p></p><p><mi>ϕ</mi><mn>0</mn><mi>M</mi></p><p></p><p></p><p></p>; the ratio between the final and the initial volume; the ratio between the major semi-axis, Δ<i>x</i>, and the two minor semi-axes, Δ<i>y</i> and Δ<i>z</i>, defined as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0132887#pone.0132887.g004" target="_blank">Fig 4</a>.<p></p