Sull’utilizzo dell’energia cinetica per produzione additiva: primi risultati di prove di fatica e confronto con lavorazioni SLM

Il cold spray (CS) è una tecnica di rivestimento a freddo in cui la deposizione delle polveri avviene grazie all’impatto ad alta velocità delle particelle contro un substrato e alla conseguente elevata deformazione plastica, con l’instaurarsi delle condizioni di instabilità adiabatica di taglio. Nel presente lavoro sono stati considerati provini in In718 prodotti con CS e con SLM, sottoposti a diversi trattamenti termici, a valle della lavorazione dei provini. La caratterizzazione dei provini ha compreso l’analisi microstrutturale, la misura degli sforzi residui e della la porosità, mentre le prove meccaniche hanno previsto prove di trazione statiche e di fatica assiale. I risultati mostrano caratteristiche e resistenza comparabili a quelle dei provini SLM, suggerendo che il CS, grazie alla minore temperatura del processo e al ridotto impegno energetico, possa divenire una tecnologia additiva alternativa o complementare rispetto alle più consolidate tecnologie laser

High prevalence and two dominant host-specific genotypes of Coxiella burnetii in U.S. milk

BackgroundCoxiella burnetii causes Q fever in humans and Coxiellosis in animals; symptoms range from general malaise to fever, pneumonia, endocarditis and death. Livestock are a significant source of human infection as they shed C. burnetii cells in birth tissues, milk, urine and feces. Although prevalence of C. burnetii is high, few Q fever cases are reported in the U.S. and we have a limited understanding of their connectedness due to difficulties in genotyping. Here, we develop canonical SNP genotyping assays to evaluate spatial and temporal relationships among C. burnetii environmental samples and compare them across studies. Given the genotypic diversity of historical collections, we hypothesized that the current enzootic of Coxiellosis is caused by multiple circulating genotypes. We collected A) 23 milk samples from a single bovine herd, B) 134 commercial bovine and caprine milk samples from across the U.S., and C) 400 bovine and caprine samples from six milk processing plants over three years.ResultsWe detected C. burnetii DNA in 96% of samples with no variance over time. We genotyped 88.5% of positive samples; bovine milk contained only a single genotype (ST20) and caprine milk was dominated by a second type (mostly ST8).ConclusionsThe high prevalence and lack of genotypic diversity is consistent with a model of rapid spread and persistence. The segregation of genotypes between host species is indicative of species-specific adaptations or dissemination barriers and may offer insights into the relative lack of human cases and characterizing genotypes

The application of adjuvant autologous antravesical macrophage cell therapy vs. BCG in non-muscle invasive bladder cancer: a multicenter, randomized trial

<p>Abstract</p> <p>Introduction</p> <p>While adjuvant immunotherapy with Bacille Calmette Guérin (BCG) is effective in non-muscle-invasive bladder cancer (BC), adverse events (AEs) are considerable. Monocyte-derived activated killer cells (MAK) are discussed as essential in antitumoural immunoresponse, but their application may imply risks. The present trial compared autologous intravesical macrophage cell therapy (BEXIDEM^®) to BCG in patients after transurethral resection (TURB) of BC.</p> <p>Materials and methods</p> <p>This open-label trial included 137 eligible patients with TaG1-3, T1G1-2 plurifocal or unifocal tumours and ≥ 2 occurrences within 24 months and was conducted from June 2004 to March 2007. Median follow-up for patients without recurrence was 12 months. Patients were randomized to BCG or mononuclear cells collected by apheresis after ex vivo cell processing and activation (BEXIDEM). Either arm treatment consisted of 6 weekly instillations and 2 cycles of 3 weekly instillations at months 3 and 6. Toxicity profile (primary endpoint) and prophylactic effects (secondary endpoint) were assessed.</p> <p>Results</p> <p>Patient characteristics were evenly distributed. Of 73 treated with BCG and 64 with BEXIDEM, 85% vs. 45% experienced AEs and 26% vs. 14% serious AEs (SAE), respectively (p < 0.001). Recurrence occurred significantly less frequent with BCG than with BEXIDEM (12% vs. 38%; p < 0.001).</p> <p>Discussion</p> <p>This initial report of autologous intravesical macrophage cell therapy in BC demonstrates BEXIDEM treatment to be safe. Recurrence rates were significantly lower with BCG however. As the efficacy of BEXIDEM remains uncertain, further data, e.g. marker lesions studies, are warranted.</p> <p>Trial registration</p> <p>The trial has been registered in the ISRCTN registry <url>http://isrctn.org</url> under the registration number ISRCTN35881130.</p

Intravesical Treatments of Bladder Cancer: Review

For bladder cancer, intravesical chemo/immunotherapy is widely used as adjuvant therapies after surgical transurethal resection, while systemic therapy is typically reserved for higher stage, muscle-invading, or metastatic diseases. The goal of intravesical therapy is to eradicate existing or residual tumors through direct cytoablation or immunostimulation. The unique properties of the urinary bladder render it a fertile ground for evaluating additional novel experimental approaches to regional therapy, including iontophoresis/electrophoresis, local hyperthermia, co-administration of permeation enhancers, bioadhesive carriers, magnetic-targeted particles and gene therapy. Furthermore, due to its unique anatomical properties, the drug concentration-time profiles in various layers of bladder tissues during and after intravesical therapy can be described by mathematical models comprised of drug disposition and transport kinetic parameters. The drug delivery data, in turn, can be combined with the effective drug exposure to infer treatment efficacy and thereby assists the selection of optimal regimens. To our knowledge, intravesical therapy of bladder cancer represents the first example where computational pharmacological approach was used to design, and successfully predicted the outcome of, a randomized phase III trial (using mitomycin C). This review summarizes the pharmacological principles and the current status of intravesical therapy, and the application of computation to optimize the drug delivery to target sites and the treatment efficacy

Fracture Toughness of Cold Sprayed Pure Metals

The study of fracture toughness of pure Al, Cu, Ni and Ti deposited by cold spray was performed in order to obtain a fundamental understanding of the damage process and quantify the material performance. Rectangular specimens cut from self-standing deposits with fatigue pre-cracks were tested in three-point bending. The KIC values were obtained from J-R curves following the ASTM E1820 standard. The stress–strain behavior of the tested material was obtained from supplementary four-point bending. The cold spray deposits exhibited significantly lower fracture toughness than the corresponding wrought materials. The reduction was more pronounced for coatings with limited ductility (Ti and Cu), where the fracture toughness reached less than 12% of the wrought counterpart only. The higher ductility coatings of Al and Ni possessed fracture toughness of 18–25% of the wrought reference materials. The performed fractographic analysis revealed inter-particular decohesion as the major failure mode

3D modelling of the deposit profile in cold spray additive manufacturing

New fields of application are coming along at an outstanding pace for cold spray deposition. More recently cold spray is being introduced as an additive manufacturing method that supersonically accelerates microparticles to induce bonding via severe plastic deformation. However, the thriving of cold spray as a widespread additive manufacturing technology with high production rates is still limited by inadequate geometrical control of the deposit shape. Thus, to establish cold spray in the additive manufacturing sector, substantial development is still required regarding digitalization and automatization of the process. To take a further step towards gaining control on the deposit geometry, present study reports the development of a 3D model able to simulate the cold spray deposit profile. The physical basis of the model is represented by a partial differential equation, which describes the deposit profile evolution as the number of passes grows. The model offers total freedom regarding the choice of the nozzle trajectory and the substrate geometry. The effects of the various process parameters, namely the number of scanning passes, spray angle, scanning speed and stand-off distance are implemented and realistically reflected in the model. More complex conditions like superimposed tracks with different spray angles, curved substrates, shadow effect and non-Gaussian profiles have been effectively simulated. The developed model has been validated with a wide range of experiments, demonstrating high accuracy and notable potential to promote the digitalization of cold spray additive manufacturing

Tailoring cold spray additive manufacturing of steel 316 L for static and cyclic load-bearing applications

Thanks to the low working temperature, less product size limitations and one order of magnitude higher deposition rates compared to the established additive manufacturing techniques, more attention has been brought to the potential of cold spraying for additive manufacturing. As a process dealing with deformation of solid particles possibly leaving non-bonded interfaces and causing work hardening, any optimization should (i) adjust spray parameters to obtain high performance as-sprayed parts and (ii) tune ductility and internal stresses by post-treatments. The present study first deals with strategies to optimize spray parameters for fabrication of high performance steel 316 L deposits. Next, the performances of deposits are further adjusted by various heat treatments. The structural strength of the freestanding samples before and after the heat treatments is evaluated under static and cyclic axial loading and supported by fatigue crack growth rate analysis. The results highlight the feasibility of obtaining high quality steel 316 L deposits using N2 as process gas, rather than the costly He that is commonly suggested. This study demonstrates the potential of cold spraying to be used for deposition of freeform structural components with a static strength comparable to that of bulk and laser-based additive manufactured materials and a fatigue strength similar to that of bulk cast material

A numerical Approach to design and develop freestanding porous structures through cold spray multi-material deposition

Cold spray is a solid-state particle deposition technique with a wide range of applications for coating, repair and additive manufacturing. Cold spray parameters are normally tuned to obtain deposits with minimal porosity and thus highest strength. However, there are specific applications such as biomedical prostheses, heat sinks and energy absorbing products, where a higher exposed surface area can lead to enhanced performance, rendering porosity a desirable feature. Few recent studies have experimentally evaluated the potential of cold spray technology for obtaining porous deposits. To enhance the efficiency of these approaches, here we developed a detailed numerical framework that can determine the topological and mechanical features of cold spray porous deposits. A series of combined Eulerian-Lagrangian finite element models were developed considering a multi-material feedstock, one constituent of which served as a porogen. Different powder blends of pure Ti mixed with either Al or Cu, as the sacrificial powder, with varying volumetric fractions were analysed. A novel post-processing approach was developed to remove the sacrificial powder and extract distinct characteristic indicators from the simulations' output; these indices include porosity and structural connectivity of the remaining Ti structure. Equivalent plastic strain was considered as an index to assess the strength of the resultant deposit. The obtained data regarding particle deformation were in agreement with preliminary experimental tests. The numerical results revealed that Ti-Cu combinations can yield deposits with higher Ti particle deformation compared to the Ti-Al blend and hence, lead to a better inter-particle bonding. This study presents a robust numerical approach for selection of cold spray process parameters towards obtaining coatings and freestanding porous metal parts with modulated porosity, connectivity and strength