Numerical Modeling of a Sustainable Solid-State Recycling of Aluminum Scraps by Means of Friction Stir Extrusion Process.

One of the most important purposes of the modern industry is a sustainable production, considering the minimization of the energy and of the raw materials used, together with the reduction of polluting emissions. In this context, Friction Stir Extrusion stands out, since it allows to obtain extrusions starting from metal scraps deriving from traditional mechanical machining processes (e.g., chips deriving from cutting operations), heated only by the friction generated between the scraps and the tool, so avoiding the material melting phase. Given the complexity of this new kind of process, the objective of this research is the study of the bonding conditions considering both the heat and the stresses generated during the process under different working parameters, namely tool rotational and descent speeds. As a result, the combined approach involving the Finite Element Analysis and the Piwnik and Plata criterion proves to be a valid tool for forecasting if bonding phenomenon occurs and how it is influenced by the process parameters. The results have also demonstrated that it is possible to achieve completely massive pieces between 500 rpm and 1200 rpm, but at different tool descent speeds. Specifically, up to 1.2 mm/s for 500 rpm and just over 2 mm/s for 1200 rpm.

Discrete-event simulation study of a COVID-19 mass vaccination centre.

The global spread of COVID-19 and the declaration of the pandemic status made by the World Health Organization (WHO) led to the establishment of mass vaccination campaigns. The challenges posed by the request to immunise the entire population necessitated the set-up of new vaccination sites, named Mass Vaccination Centres (MVCs), capable of handling large numbers of patients rapidly and safely. The present study focused on the evolution of MVC performances, in terms of the maximum number of vaccinated patients and primary resource utilisation ratio, while involving statistics belonging to the patient dimension. The research involved the creation of a digital model of the MVC, using the Discrete-Event Simulation (DES) software (FlexSim Healthcare), and consequent what-if analyses. The results were derived from the study of an existing facility, located within a sports centre in the province of Bergamo (Italy) and operating with an advanced MVC organisational model, in compliance with the national anti-SARS-CoV-2 legislation. The research provided additional evidence on innovative MVC organisational models, identifying an optimal MVC configuration. Besides, the obtained results remain relevant for countries where a significant portion of the population has not yet addressed the emergency, either for upcoming vaccination treatments. Furthermore, the methodology adopted in the present article proved to be a valuable resource in the analysis of the healthcare processes.

Special Issue of Materials focusing on "Finite Element Analysis and Models of Sustainable Manufacturing Processes".

We believe that the chosen topic is nowadays extremely current and of great interest [...].

A Comparison between Finite Element Model (FEM) Simulation and an Integrated Artificial Neural Network (ANN)-Particle Swarm Optimization (PSO) Approach to Forecast Performances of Micro Electro Discharge Machining (Micro-EDM) Drilling.

Artificial Neural Network (ANN), together with a Particle Swarm Optimization (PSO) and Finite Element Model (FEM), was used to forecast the process performances for the Micro Electrical Discharge Machining (micro-EDM) drilling process. The integrated ANN-PSO methodology has a double direction functionality, responding to different industrial needs. It allows to optimize the process parameters as a function of the required performances and, at the same time, it allows to forecast the process performances fixing the process parameters. The functionality is strictly related to the input and/or output fixed in the model. The FEM model was based on the capacity of modeling the removal process through the mesh element deletion, simulating electrical discharges through a proper heat-flux. This paper compares these prevision models, relating the expected results with the experimental data. In general, the results show that the integrated ANN-PSO methodology is more accurate in the performance previsions. Furthermore, the ANN-PSO model is faster and easier to apply, but it requires a large amount of historical data for the ANN training. On the contrary, the FEM is more complex to set up, since many physical and thermal characteristics of the materials are necessary, and a great deal of time is required for a single simulation.

Effect of Load on the Corrosion Behavior of Friction Stir Welded AA 7075-T6 Aluminum Alloy.

The paper focuses on the corrosion behavior of aluminum joints made by friction stir welding as a function of loading conditions. A four-points bend-beam test, constant loading test, and slow strain-rate test were carried out on AA 7075-T6 alloy in aerated NaCl 35g/L solution at room temperature monitoring the free corrosion potential. The penetration depth of the intergranular attack was deeper after the four-point bent-beam tests compared to all the other testing techniques. Preferential dissolution along the grain boundaries was found in the heat-affected zone and the attack follows the elongated grains structure along the rolling direction. However, no stress-corrosion cracking phenomena were detected. No relevant stress corrosion cracking (SCC) crack embryos propagation was noticed under uniaxial tensile tests-both constant loading and slow strain-rate tests-manly due to the high dissolution rate occurring at the crack tip which promoted premature shear ruptures.

Stress Corrosion Cracking of Friction Stir-Welded AA-2024 T3 Alloy.

The paper is devoted to the study of stress corrosion cracking phenomena in friction stir welding AA-2024 T3 joints. Constant load (CL) cell and slow strain rate (SSR) tests were carried out in aerated NaCl 35 g/L solution. During the tests, open circuit potential (OCP) and electrochemical impedance spectroscopy (EIS) were measured in the different zones of the welding. The results evidenced initial practical nobilty of the nugget lower compared to both heat-affected zone and the base metal. This effect can be mainly ascribed to the aluminum matrix depletion in copper, which precipitates in form of copper-rich second phases. In this zones, no stress corrosion cracking was noticed, but well-evident stress-enhanced intergranular corrosion occurred. This is due to the uneven distribution of platic deformation during the slow strain rate tests. Higher strain values are localized at the heat affected zone, where softening occurs. On the contrary, stress values at the nugget are not sufficient to favor both the initiation and propagation of stress corrosion cracks. In the range of processing parameter studied in this experimental work, the stress corrosion cracking susceptibility of the friction stir welding (FSW)-ed alloy is then similar to that of the base metal.

Cost Index Model for the Process Performance Optimization of Micro-EDM Drilling on Tungsten Carbide.

The present work deals with the execution of through micro-holes on tungsten carbide plates using a micro-electrical discharge machining (micro-EDM) machine. The experiments were carried out by varying peak current, voltage and frequency in order to achieve suitable technology windows. Tubular electrodes, made of two different materials (tungsten carbide and brass), were used. The investigation focuses on the influence of variable process parameters on the process performances and their optimization. The performance indicators taken into account were Material Removal Rate (MRR) and Tool Wear Ratio (TWR). A general model based on a cost index was defined for the process performances optimization and the optimal conditions were identified through the minimization of the objective function.

Thermo-Mechanical Characterization of Friction Stir Spot Welded AA7050 Sheets by Means of Experimental and FEM Analyses.

The present study was carried out to evaluate how the friction stir spot welding (FSSW) process parameters affect the temperature distribution in the welding region, the welding forces and the mechanical properties of the joints. The experimental study was performed by means of a CNC machine tool obtaining FSSW lap joints on AA7050 aluminum alloy plates. Three thermocouples were inserted into the samples to measure the temperatures at different distance from the joint axis during the whole FSSW process. Experiments was repeated varying the process parameters, namely rotational speed, axial feed rate and plunging depth. Axial welding forces were measured during the tests using a piezoelectric load cell, while the mechanical properties of the joints were evaluated by executing shear tests on the specimens. The correlation found between process parameters and joints properties, allowed to identify the best technological window. The data collected during the experiments were used to validate a simulation model of the FSSW process, too. The model was set up using a 2D approach for the simulation of a 3D problem, in order to guarantee a very simple and practical solution for achieving results in a very short time. A specific external routine for the calculation of the thermal energy due to friction acting between pin and sheet was developed. An index for the prediction of the joint mechanical properties using the FEM simulations was finally presented and validated.

Reproducibility of liver iron concentration measured on a biopsy sample: a validation study in vivo.

Determination of liver iron concentration is essential to predict iron related tissue damage and to guide chelation therapy. To assess the reliability of a single biopsy iron concentration determination in representing the whole liver iron concentration, we conducted a prospective study performing two immediately successive liver biopsies from 61 noncirrhotic, iron overloaded thalassemia patients, directing the needle to different direction from the same skin cut. The correlation among sample biopsies was determined by both regression analysis and the Bland-Altman method. The results showed that overall correlation between the two samples was high (Pearson's coefficient of correlation r = 0.970, P < 0.0001; 95% CI 0.951-0.981; R(2) = 0.941). To evaluate if sample dimension had an impact on the analysis we analyzed separately biopsy couples were both sample gross weight were ≥1 mg dry weight (n = 16) from the others [one or both had a specimen gross weight <1 mg dry weight (n = 45)]. In the first case, correlation coefficient r was equal to 0.998 (P < 0.0001; 95% CI: 0.995-0.999; R(2) = 0.996) while in the latter was 0.960 (P < 0.0001; 95% CI: 0.928-0.977; R(2) = 0.921). In no instance second specimen prediction interval was outside the interval implying different prognostic and therapeutic decision if both liver samples gross weight were ≥1 mg dry weight. The Bland-Altman plot analysis showed the same trend observed using Pearson's correlation coefficient in the analyzed sample categories. Hepatic iron concentration determined in "good quality" biopsy specimen (i.e. sample gross weight ≥1 mg dry weight) is a reliable indicator of whole liver iron concentration.

Hematopoietic stem cell transplantation in thalassemia major and sickle cell disease: indications and management recommendations from an international expert panel.

Thalassemia major and sickle cell disease are the two most widely disseminated hereditary hemoglobinopathies in the world. The outlook for affected individuals has improved in recent years due to advances in medical management in the prevention and treatment of complications. However, hematopoietic stem cell transplantation is still the only available curative option. The use of hematopoietic stem cell transplantation has been increasing, and outcomes today have substantially improved compared with the past three decades. Current experience world-wide is that more than 90% of patients now survive hematopoietic stem cell transplantation and disease-free survival is around 80%. However, only a few controlled trials have been reported, and decisions on patient selection for hematopoietic stem cell transplantation and transplant management remain principally dependent on data from retrospective analyses and on the clinical experience of the transplant centers. This consensus document from the European Blood and Marrow Transplantation Inborn Error Working Party and the Paediatric Diseases Working Party aims to report new data and provide consensus-based recommendations on indications for hematopoietic stem cell transplantation and transplant management.

Third party cord blood transplant boosts autologous hematopoiesis in a case of persistent bone marrow aplasia after double transplant failure for B-thalassemia major.

A 9-year-old female received an allogeneic stem cell transplant (SCT) from an ABO-incompatible HLA-matched sibling for ß-thalassemia major, without achieving a complete donor chimerism. Subsequently, the patient received five donor lymphocyte infusions, without increasing donor chimerism, and autologous SCT. Due to the persistent bone marrow aplasia, the patient received a second allogeneic SCT from the same donor without obtaining any engrafment. After the double transplant failure, we performed an unrelated transplant from a full-matched umbilical cord blood (UCBT) without administering any neither conditioning regimen nor GVHD prophylaxis. Forty days after UCBT, trilinear engraftment was documented. Surprisingly, the hematopoietic reconstitution was related to the re-expansion of the autologous (beta-thalassemic) hematopoietic stem cell, as documented by chimerism studies. At present, 30 months after UCBT, there is stable hematopoietic autologous reconstitution. This is the first description of the restoration of autologous hematopoiesis obtained with UCBT in a thalassemia-major patient after a double transplant failure.

Influence of Material Microstructures in Micromilling of Ti6Al4V Alloy.

In the most recent decades the introduction of unconventional machining processes allowed the development of micromachining techniques. In this work, the influence of material microstructures on the micromilling process was investigated. Ti6Al4V alloy was selected as workpiece material since it is a very common material for micro applications and because its duplex microstructure can be easily changed by proper thermal treatments. Four different microstructures (namely bimodal, fully equiaxed, fully lamellar and mill annealed) were obtained through recrystallization annealing treatments carried out at different times and temperatures. The mechanical properties of the samples were assessed by microhardness measurements. Nano-indentations were also performed on single grains to understand how the different hardness of phases and structures present in the Ti6Al4V alloy can affect the micromilling process. Microchannels using two flute flat end mills with a diameter equal to 200 µm were realized on the treated samples. Two different feed-per-tooth values were used during the tests. Cutting force, channel shape and burr dimension were investigated. Morphological and energy dispersive spectroscopy (EDS) analyses were performed on tools by means of a scanning electron microscope (SEM): in this way the phenomena mainly influencing the tool status were also identified. Lower cutting forces and reduced tool wear were observed when working fully lamellar microstructures compared to the other ones.

Evaluation of Superficial and Dimensional Quality Features in Metallic Micro-Channels Manufactured by Micro-End-Milling.

Miniaturization encourages the development of new manufacturing processes capable of fabricating features, like micro-channels, in order to use them for different applications, such as in fuel cells, heat exchangers, microfluidic devices and micro-electromechanical systems (MEMS). Many studies have been conducted on heat and fluid transfer in micro-channels, and they appeared significantly deviated from conventional theory, due to measurement errors and fabrication methods. The present research, in order to deal with this opportunity, is focused on a set of experiments in the micro-milling of channels made of aluminum, titanium alloys and stainless steel, varying parameters, such as spindle speed, depth of cut per pass (ap), channel depth (d), feed per tooth (fz) and coolant application. The experimental results were analyzed in terms of dimensional error, channel profile shape deviation from rectangular and surface quality (burr and roughness). The micro-milling process was capable of offering quality features required on the micro-channeled devices. Critical phenomena, like run-out, ploughing, minimum chip thickness and tool wear, were encountered as an explanation for the deviations in shape and for the surface quality of the micro-channels. The application of coolant and a low depth of cut per pass were significant to obtain better superficial quality features and a smaller dimensional error. In conclusion, the integration of superficial and geometrical features on the study of the quality of micro-channeled devices made of different metallic materials contributes to the understanding of the impact of calibrated cutting conditions in MEMS applications.

Recipient CTLA-4*CT60-AA genotype is a prognostic factor for acute graft-versus-host disease in hematopoietic stem cell transplantation for thalassemia.

Polymorphisms of the cytotoxic T-lymphocyte antigen-4 gene (CTLA-4) have been associated with autoimmune diseases and it has recently been reported that donor genotypes correlate with the outcome of allogeneic hematopoietic stem cell transplantation in leukemia patients. With the aim of confirming this finding in thalassemia patients, we investigated the influence of genotype distribution of 3 CTLA-4 gene polymorphisms in 72 thalassemia patients and their unrelated donors. A significant association was observed for recipient CT60-AA genotype and onset of grade II-IV (63.2% vs 24.5%; p = 0.001) and grade III-IV (36.4% vs 7.6%; p = 0.005) acute graft-versus-host disease (aGVHD). The same association was observed for the 88-base-pair allele of the CTLA-4 (AT)n polymorphism, which was determined to be in complete linkage disequilibrium with the CT60 A allele. Multinomial Cox regression demonstrated that this association was independent of CT60 donor genotypes or other risk factors (p = 0.016; hazard ratio = 2.8). Our data confirm that the genetic variability in CTLA-4 is an important prognostic factor for aGVHD and suggest that some of the risk factors for this complication are generated by recipient cells that persist after the myeloablative conditioning regimen.

Interactions between killer immunoglobulin-like receptors and their human leucocyte antigen Class I ligands influence the outcome of unrelated haematopoietic stem cell transplantation for thalassaemia: a novel predictive algorithm.

In a study conducted on 114 patients undergoing unrelated donor haematopoietic stem cell transplantation (HSCT) for thalassaemia, we observed that the lack of activating killer immunoglobulin-like receptors (KIRs) on donor natural killer (NK) cells significantly increased the risk of graft-versus-host disease (GvHD) [hazard risk (HR) 4.2, 95% confidence interval (CI) 1.7-10.1, P = 0.002] and transplantation-related mortality (HR 4.7, 95% CI 1.6-14.2, P = 0.01). The risk of GvHD furthermore increased when recipients heterozygous for HLA-C KIR ligand groups (C1/C2) were transplanted from donors completely lacking activating KIRs (HR 6.1, 95% CI 1.9-19.2, P = 0.002). We also found that the risk of rejection was highest when the recipient was homozygous for the C2 HLA-KIR ligand group and the donor carried two or more activating KIRs (HR 6.8, 95% CI 1.9-24.4, P = 0.005). By interpolating the number of donor activating KIRs with recipient HLA-C KIR ligands, we created an algorithm capable of stratifying patients according to the immunogenetic risk of complications following unrelated HSCT. In clinical practice, this predictive tool could serve as an important supplement to clinical judgement and decision-making.

BeEAM (bendamustine, etoposide, cytarabine, melphalan) before autologous stem cell transplantation is safe and effective for resistant/relapsed lymphoma patients.

We designed a phase 1-2 study to evaluate the safety and the efficacy of increasing doses of bendamustine (160 mg/m², 180 mg/m², and 200 mg/m² given on days -7 and -6) coupled with fixed doses of etoposide, cytarabine, and melphalan (BeEAM regimen) as the conditioning regimen to autologous stem cell transplantation for resistant/relapsed lymphoma patients. Forty-three patients (median age, 47 years) with non-Hodgkin (n = 28) or Hodgkin (n = 15) lymphoma were consecutively treated. Nine patients entered the phase 1 study; no patients experienced a dose-limiting toxicity. Thirty-four additional patients were then treated in the phase 2. A median number of 6 × 106 CD34(+) cells/kg (range, 2.4-15.5) were reinfused. All patients engrafted, with a median time to absolute neutrophil count > 0.5 × 109/L of 10 days. The 100-day transplantation-related mortality was 0%. After a median follow-up of 18 months, 35 of 43 patients (81%) are in complete remission, whereas 6 of 43 relapsed and 2 of 43 did not respond. Disease type (non-Hodgkin lymphomas vs Hodgkin disease) and disease status at transplantation (chemosensitive vs chemoresistant) significantly influenced DFS (P = .01; P = .007). Remarkably, 4 of 43 (9%) patients achieved the first complete remission after receiving the high-dose therapy with autologous stem cell transplantation. In conclusion, the new BeEAM regimen is safe and effective for heavily pretreated lymphoma patients. The study was registered at European Medicines Agency (EudraCT number 2008-002736-15).

Status of donor-recipient HLA class I ligands and not the KIR genotype is predictive for the outcome of unrelated hematopoietic stem cell transplantation in beta-thalassemia patients.

Several studies have investigated the role played by killer immunoglobulin-like receptors (KIRs) and their ligands on the outcome of hematopoietic stem cell transplantation (HSCT) in patients affected by oncohematologic diseases. However, the interpretation of the results of these studies is considerably hampered by the heterogeneity of the diseases, disease status at transplantation, and the different protocols employed for both conditioning and graft-versus-host disease (GVHD) prophylaxis. To better define the role of KIRs in HSCT, we studied KIR genotypes and HLA class I ligands in a homogeneous group of 45 thalassemia patients transplanted with bone marrow cells from an HLA-identical, unrelated donor. Patients that were heterozygotes for HLA-Cw groups 1 (HLA-Cw(Asn80)) and 2 (HLA-Cw(Lys80)) had a higher risk of developing acute GVHD than C1/C1 or C2/C2 homozygotes (relative risk [RR] = 8.75; 95% confidence interval [CI]: 1.63-46.76; P = .007). Vice versa, all patients who experienced primary/secondary graft failure were C1/C1 or C2/C2 homozygotes (RR = 20.45; 95% CI = 1.08-384.24; P = .009). Moreover, the presence of the HLA-A11 antigen conferred protection against GVHD (0% versus 35%, P = .02). Our results suggest that C1/C2 heterozygosity, may favor the development of donor alloreactivity and thereby increase the risk of GVHD. Conversely, C1/C1 and C2/C2 homozygosity seems to reduce the risk of GVHD but may increase the incidence of graft rejection. These data may be helpful in tailoring the intensity of GVHD prophylaxis and conditioning regimens in thalassemia patients receiving HSCT from an HLA-identical volunteer donor.

Graft rejection after unrelated donor hematopoietic stem cell transplantation for thalassemia is associated with nonpermissive HLA-DPB1 disparity in host-versus-graft direction.

The success of allogeneic hematopoietic stem cell transplantation (HSCT) from matched unrelated donors (UDs) for beta-thalassemia may be hampered by the occurrence of graft rejection. Here, we show that the rate of this complication can be reduced by selecting 5-loci HLA-matched donors without nonpermissive mismatches at HLA-DPB1, defined according to an algorithm previously described and based on principles of central T-cell tolerance. Seventy-two consecutive patients and their UDs, prospectively selected for matching at the allelic level for HLA-A, -B, -C, -DRB, and -DQB1 loci, were enrolled in the analysis. These pairs were either DPB1 matched/permissively mismatched (n = 45, control group) or had at least one nonpermissive DPB1 mismatch in the host-versus-graft (HvG; n = 17) or in the graft-versus-host (GvH; n = 10) direction. In multivariate analysis, the risk of rejection was significantly increased in the group with HvG disparity (RR = 7.42; 95% CI = 1.29-42.68; P = .02) as compared to the control group. A lower, statistically significant, probability of thalassemia-free survival was found in patients belonging to the HvG group as compared to controls (RR = 5.15; 95% CI = 1.58-16.82; P = .01). These data suggest that in patients with thalassemia, the incidence of graft failure after HSCT may be reduced by appropriate selection of UDs, with such selection taking into account the functional rules of immunogenetics.

Unrelated bone marrow transplantation for beta-thalassemia patients: The experience of the Italian Bone Marrow Transplant Group.

Bone marrow transplantation (BMT) remains the only potentially curative treatment for patients with thalassemia major. However, most candidates for BMT do not have a suitable family donor. In order to evaluate whether BMT from an HLA-matched unrelated volunteer donor can offer a probability of cure comparable to that obtained when the donor is a compatible sibling, we carried out a study involving 68 thalassemia patients transplanted in six Italian BMT Centers. Thirty-three males and 35 females (age range, 2-37 years; median age, 15) were transplanted from unrelated volunteer donors, all selected using high-resolution molecular typing of both HLA class I and II loci. Fourteen patients were classified in risk class 1; 16 in risk class 2; and 38 in risk class III of the Pesaro classification system. Nine patients (13%) had either primary or secondary graft failure. Fourteen patients (20%) died from transplant-related causes. Grade II-IV acute graft-versus-host disease (GVHD) developed in 24 cases (40%), and chronic GVHD in 10 cases (18%). Overall survival (OS) in the cohort of 68 patients was 79.3% (CI 67-88%), whereas the Kaplan-Meier estimates of disease-free survival (DFS) with transfusion independence was 65.8% (CI 54-77%). In the group of 30 thalassemic patients in risk classes 1 and 2, the probability of OS and DFS were 96.7% (CI 90-100%) and 80.0% (CI 65-94%), respectively, whereas in the 38 patients in class 3 OS was 65.2% (CI 49-80%) and DFS was 54.5% (CI 38-70%). These data show that when donor selection is based on stringent compatibility criteria, the results of unrelated transplantation in thalassemia patients are comparable to those obtained when the donor is a compatible sibling.