Free-form deformation, mesh morphing and reduced-order methods: enablers for efficient aerodynamic shape optimisation

The work provides an integrated pipeline for the model order reduction of turbulent flows around parametrised geometries in aerodynamics. In particular, Free-Form Deformation is applied for geometry parametrisation, whereas two different reduced-order models based on Proper Orthogonal Decomposition (POD) are employed in order to speed-up the full-order simulations: the first method exploits POD with interpolation, while the second one is based on domain decomposition. For the sampling of the parameter space, we adopt a Greedy strategy coupled with Constrained Centroidal Voronoi Tessellations, in order to guarantee a good compromise between space exploration and exploitation. The proposed framework is tested on an industrially relevant application, i.e. the front-bumper morphing of the DrivAer car model, using the finite-volume method for the full-order resolution of the Reynolds-Averaged Navier-Stokes equations

Driver mutations (JAK2V617F, MPLW515L/K or CALR), pentraxin-3 and C-reactive protein in essential thrombocythemia and polycythemia vera

BACKGROUND: The driver mutations JAK2V617F, MPLW515L/K and CALR influence disease phenotype of myeloproliferative neoplasms (MPNs) and might sustain a condition of chronic inflammation. Pentraxin 3 (PTX3) and high-sensitivity C-reactive protein (hs-CRP) are inflammatory biomarkers potentially useful for refining prognostic classification of MPNs. METHODS: We evaluated 305 with essential thrombocythemia (ET) and 172 polycythemia vera (PV) patients diagnosed according to the 2016 WHO criteria and with full molecular characterization for driver mutations. RESULTS: PTX3 levels were significantly increased in carriers of homozygous JAK2V617F mutation compared to all the other genotypes and triple negative ET patients, while hs-CRP levels were independent of the mutational profile. The risk of haematological evolution and death from any cause was about 2- and 1.5-fold increased in individuals with high PTX-3 levels, while the thrombosis rate tended to be lower. High hs-CRP levels were associated with risk of haematological evolution, death and also major thrombosis. After sequential adjustment for potential confounders (age, gender, diagnosis and treatments) and the presence of JAK2V617F homozygous status, high hs-CRP levels remained significant for all outcomes, while JAK2V617F homozygous status as well as treatments were the factors independently accounting for adverse outcomes among patients with high PTX3 levels. CONCLUSIONS: These results provide evidence that JAK2V617F mutation influences MPN-associated inflammation with a strong correlation between allele burden and PTX3 levels. Plasma levels of hs-CRP and PTX3 might be of prognostic value for patients with ET and PV, but their validation in future prospective studies is needed

Pilot scale validation campaign of gel dosimetry for pre-treatment quality assurance in stereotactic radiotherapy

Purpose: Complex stereotactic radiotherapy treatment plans require prior verification. A gel dosimetry system was developed and tested to serve as a high-resolution 3D dosimeter for Quality Assurance (QA) purposes.Materials and Methods: A modified version of a polyacrylamide polymer gel dosimeter based on chemical response inhibition was employed. Different sample geometries (cuvettes and phantoms) were manufactured for calibration and QA acquisitions. Irradiations were performed with a Varian Trilogy linac, and analyses of irradiated gel dosimeters were performed via MRI with a 1.5 T Philips Achieva at 1 mm3 or 2 mm3 isotropic spatial resolution. To assess reliability of polymer gel data, 54 stereotactic clinical treatment plans were delivered both on dosimetric gel phantoms and on the Delta4 dosimeter. Results from the two devices were evaluated through a global gamma index over a range of acceptance criteria and compared with each other.Results: A quantitative and tunable control of dosimetric gel response sensitivity was achieved through chemical inhibition. An optimized MRI analysis protocol allowed to acquire high resolution phantom dose data in time -frames of approximate to 1 h. Conversion of gel dosimeter data into absorbed dose was achieved through internal calibration. Polymer gel dosimeters (2 mm3 resolution) and Delta4 presented an agreement within 4.8 % and 2.7 % at the 3 %/1 mm and 2 %/2 mm gamma criteria, respectively.Conclusions: Gel dosimeters appear as promising tools for high resolution 3D QA. Added complexity of the gel dosimetry protocol may be justifiable in case of small target volumes and steep dose gradients

Driver mutations (JAK2V617F, MPLW515L/K or CALR), pentraxin-3 and C-reactive protein in essential thrombocythemia and polycythemia vera

Background: The driver mutations JAK2V617F, MPLW515L/K and CALR influence disease phenotype of myeloproliferative neoplasms (MPNs) and might sustain a condition of chronic inflammation. Pentraxin 3 (PTX3) and high-sensitivity C-reactive protein (hs-CRP) are inflammatory biomarkers potentially useful for refining prognostic classification of MPNs. Methods: We evaluated 305 with essential thrombocythemia (ET) and 172 polycythemia vera (PV) patients diagnosed according to the 2016 WHO criteria and with full molecular characterization for driver mutations. Results: PTX3 levels were significantly increased in carriers of homozygous JAK2V617F mutation compared to all the other genotypes and triple negative ET patients, while hs-CRP levels were independent of the mutational profile. The risk of haematological evolution and death from any cause was about 2- and 1.5-fold increased in individuals with high PTX-3 levels, while the thrombosis rate tended to be lower. High hs-CRP levels were associated with risk of haematological evolution, death and also major thrombosis. After sequential adjustment for potential confounders (age, gender, diagnosis and treatments) and the presence of JAK2V617F homozygous status, high hs-CRP levels remained significant for all outcomes, while JAK2V617F homozygous status as well as treatments were the factors independently accounting for adverse outcomes among patients with high PTX3 levels. Conclusions: These results provide evidence that JAK2V617F mutation influences MPN-associated inflammation with a strong correlation between allele burden and PTX3 levels. Plasma levels of hs-CRP and PTX3 might be of prognostic value for patients with ET and PV, but their validation in future prospective studies is needed

Involvement of MAF/SPP1 axis in the development of bone marrow fibrosis in PMF patients

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by hyperplastic megakaryopoiesis and myelofibrosis. We recently described the upregulation of MAF (v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog) in PMF CD34+ hematopoietic progenitor cells (HPCs) compared to healthy donor. Here we demonstrated that MAF is also upregulated in PMF compared with the essential thrombocytemia (ET) and polycytemia vera (PV) HPCs. MAF overexpression and knockdown experiments shed some light into the role of MAF in PMF pathogenesis, by demonstrating that MAF favors the megakaryocyte and monocyte/macrophage commitment of HPCs and leads to the increased expression of proinflammatory and profibrotic mediators. Among them, we focused our further studies on SPP1 and LGALS3. We assessed SPP1 and LGALS3 protein levels in 115 PMF, 47 ET and 24 PV patients plasma samples and we found that SPP1 plasma levels are significantly higher in PMF compared with ET and PV patients. Furthermore, in vitro assays demonstrated that SPP1 promotes fibroblasts and mesenchymal stromal cells proliferation and collagen production. Strikingly, clinical correlation analyses uncovered that higher SPP1 plasma levels in PMF patients correlate with a more severe fibrosis degree and a shorter overall survival. Collectively our data unveil that MAF overexpression contributes to PMF pathogenesis by driving the deranged production of the profibrotic mediator SPP1

Chronic neuropsychiatric sequelae of SARS‐CoV‐2: Protocol and methods from the Alzheimer's Association Global Consortium

Introduction Coronavirus disease 2019 (COVID-19) has caused >3.5 million deaths worldwide and affected >160 million people. At least twice as many have been infected but remained asymptomatic or minimally symptomatic. COVID-19 includes central nervous system manifestations mediated by inflammation and cerebrovascular, anoxic, and/or viral neurotoxicity mechanisms. More than one third of patients with COVID-19 develop neurologic problems during the acute phase of the illness, including loss of sense of smell or taste, seizures, and stroke. Damage or functional changes to the brain may result in chronic sequelae. The risk of incident cognitive and neuropsychiatric complications appears independent from the severity of the original pulmonary illness. It behooves the scientific and medical community to attempt to understand the molecular and/or systemic factors linking COVID-19 to neurologic illness, both short and long term. Methods This article describes what is known so far in terms of links among COVID-19, the brain, neurological symptoms, and Alzheimer's disease (AD) and related dementias. We focus on risk factors and possible molecular, inflammatory, and viral mechanisms underlying neurological injury. We also provide a comprehensive description of the Alzheimer's Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 infection (CNS SC2) harmonized methodology to address these questions using a worldwide network of researchers and institutions. Results Successful harmonization of designs and methods was achieved through a consensus process initially fragmented by specific interest groups (epidemiology, clinical assessments, cognitive evaluation, biomarkers, and neuroimaging). Conclusions from subcommittees were presented to the whole group and discussed extensively. Presently data collection is ongoing at 19 sites in 12 countries representing Asia, Africa, the Americas, and Europe. Discussion The Alzheimer's Association Global Consortium harmonized methodology is proposed as a model to study long-term neurocognitive sequelae of SARS-CoV-2 infection

High Frequency of Endothelial Colony Forming Cells Marks a Non-Active Myeloproliferative Neoplasm with High Risk of Splanchnic Vein Thrombosis

Increased mobilization of circulating endothelial progenitor cells may represent a new biological hallmark of myeloproliferative neoplasms. We measured circulating endothelial colony forming cells (ECFCs) in 106 patients with primary myelofibrosis, fibrotic stage, 49 with prefibrotic myelofibrosis, 59 with essential thrombocythemia or polycythemia vera, and 43 normal controls. Levels of ECFC frequency for patient's characteristics were estimated by using logistic regression in univariate and multivariate setting. The sensitivity, specificity, likelihood ratios, and positive predictive value of increased ECFC frequency were calculated for the significantly associated characteristics. Increased frequency of ECFCs resulted independently associated with history of splanchnic vein thrombosis (adjusted odds ratio = 6.61, 95% CI = 2.54–17.16), and a summary measure of non-active disease, i.e. hemoglobin of 13.8 g/dL or lower, white blood cells count of 7.8×109/L or lower, and platelet count of 400×109/L or lower (adjusted odds ratio = 4.43, 95% CI = 1.45–13.49) Thirteen patients with splanchnic vein thrombosis non associated with myeloproliferative neoplasms were recruited as controls. We excluded a causal role of splanchnic vein thrombosis in ECFCs increase, since no control had elevated ECFCs. We concluded that increased frequency of ECFCs represents the biological hallmark of a non-active myeloproliferative neoplasm with high risk of splanchnic vein thrombosis. The recognition of this disease category copes with the phenotypic mimicry of myeloproliferative neoplasms. Due to inherent performance limitations of ECFCs assay, there is an urgent need to arrive to an acceptable standardization of ECFC assessment

Scuola media con biblioteca civica e palestra a Lumezzane, località Pieve

Pubblicata in: red., Scuola media dell’obbligo a Lumezzane di Brescia, in “Ottagono”, n. 31, dicembre 1973; L. S. d’Angiolini, Paese e fabbrica fanno scuola. Scuola media di Pieve a Lumezzane, Brescia, in “L’architettura-cronache e storia”, n. 294, aprile 1980; H. Hansen, Progetto come ricerca destinata, in “Hinterland”, n. 17, marzo 1981; E. Bordogna e G.P. Semino, Poetic responsibility and iconographic overabundance. Architecture of the last two decades, in Aa. Vv., Post-war Italian architecture, a cura di A. Christofellis, in “Architektonica themata - Architecture in Greece”, 1981; red., Architettura in Lombardia: Selezione IN/Arch, in “Abitare”, n. 222, marzo 1984; G. Canella, Gusto della falsificazione e gusto della realtà, in “Controspazio”, n. 1-2, gennaio-giugno 1985; M. Tafuri, Storia dell’architettura italiana 1944-1985, Einaudi, Torino 1986; Aa. Vv., Architettura dei luoghi urbani: nodi e margini, a cura di R. Spagnolo e G. Bertelli, Guerini e Associati, Milano 1991. Aa. Vv., Italia 60/70. Una stagione dell’architettura, Il Poligrafo, Padova 2010. Esposto in occasione della Mostra sulla città, Facoltà di Architettura di Milano, 1974 e Rassegna critica delle opere di architettura in Lombardia, Mostra dei progetti selezionati, Regione Lombardia-IN/Arch Sezione lombarda, Milano 1984. Selezionata nell’ambito della “Rassegna critica delle opere di architettura in Lombardia”, IN/Arch 1983

Scuola elementare a Cesano Boscone, località Monaca, Milano

Pubblicato in: red., Una scuola come polo di coagulo urbano. Scuola elementare a Cesano Boscone, Milano, in “L’architettura-cronache e storia”, n. 331, maggio 1983; red., Un progetto che fa scuola, in “Costruire per abitare”, n. 18, aprile 1984; red., Scuola elementare a Cesano Boscone (Milano), in “L’industria italiana del cemento”, n. 587, marzo 1985; G. Canella, Gusto della falsificazione e gusto della realtà, in “Controspazio”, n. 1-2, gennaio-giugno 1985; M. Tafuri, Storia dell’architettura italiana 1944-1985, Einaudi, Torino 1986