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Noncompressible truncal hemorrhage (NCTH) remains a leading cause of preventable death on the battlefield. Definitively managing severe NCTH requires surgery within the first hour after injury, which is difficult when evacuating casualties from remote and austere environments. During delays to surgery, hemostatic interventions that are performed prehospital can prevent coagulopathy and hemorrhagic shock and increase the likelihood that casualties survive to receive definitive care. We previously reported that a self-propelling thrombin-containing powder (SPTP) can be delivered percutaneously into the abdomen as a minimally invasive intervention and can self-disperse through pooled blood to deliver the hemostatic agents thrombin and tranexamic acid locally to noncompressible intracavitary wounds. We hypothesized that, in swine with massive NCTH, dilutional coagulopathy, and hypothermia, delivering SPTP could extend survival times.Ten swine (n = 5 per group) underwent NCTH from a Grade V liver injury following a midline laparotomy. The laparotomy was closed with sutures afterwards, creating a hemoperitoneum, and animals were managed with crystalloid fluid resuscitation, or crystalloid resuscitation and SPTP. Self-propelling thrombin-containing powder was delivered into the closed abdomen using a CO 2 -powered spray device and a catheter placed into the hemoperitoneum, entering through the upper right quadrant using the Seldinger technique. Survival to 1 and 3 hours was recorded. In an additional animal, hemorrhage was created laparoscopically, and SPTP was imaged in situ within the abdomen to visually track dispersion of the particles.Self-propelling thrombin-containing powder dispersed as far as 35 ± 5.0 cm within the abdomen. It increased survival to 1 and 3 hours (Kaplan-Meier p = 0.007 for both). The median survival time was 61 minutes with SPTP and 31 minutes without ( p = 0.016).Self-propelling thrombin-containing powder effectively disperses medications throughout a hemoperitoneum and increases survival in a model of NCTH. It is a promising strategy for nonsurgical management of NCTH, warranting further testing of its safety and efficacy.

Non-compressible intra-abdominal hemorrhage (NCIAH) is a major cause of preventable death on the battlefield and in civilian trauma. Currently, it can only be definitively managed with surgery, as there are limited strategies for controlling ongoing NCIAH in the prehospital environment. We hypothesized that a self-propelling thrombin-containing powder (SPTP) could increase survival in a swine model of NCIAH when delivered percutaneously into the closed abdomen using an engineered spray system.Nineteen swine underwent surgical laparotomy followed by a Grade V liver injury that created massive hemorrhage, before closing the abdomen with sutures. Animals either received treatment with standard of care fluid resuscitation (n=9) or the SPTP spray system (n=10), which consisted of a spray device and a 14 Fr catheter. Using the spray system, SPTP was delivered into a hemoperitoneum identified using a focused assessment with sonography in trauma (FAST) exam. Lactated Ringer's solution was administered to all animals to maintain a mean arterial pressure (MAP) of50 mmHg. The primary outcome was percentage of animals surviving at three hours following injury.In the swine model of NCIAH, a greater percentage of animals receiving SPTP survived to three hours, although differences were not significant. The SPTP spray system increased the median survival of animals from 1.6 hr in the fluid resuscitation group to 4.3 hr. The SPTP spray system delivered a total mass of 18.5 ± 1.0 g of SPTP. The mean change in intra-abdominal pressure following SPTP delivery was 5.2 ± 1.8 mmHg (mean ± SEM). The intervention time was 6.7 ± 1.7 min. No adverse effects related to the SPTP formulation or the spray system were observed. SPTP was especially beneficial in animals that had either severely elevated lactate concentrations or low mean arterial pressure of35 mmHg shortly after injury.This demonstrates proof-of-concept for use of a new minimally invasive procedure for managing NCIAH, which could extend survival time to enable patients to reach definitive surgical care.

The notochord acts as a patterning structure, playing a key role in the formation of the vertebral column, both indirectly by inducing sclerotome cell differentiation and directly by forming the nucleus pulposus of intervertebral discs. The abnormal development of the notochord results in an easy equation with a variety of birth defects. Therefore, we focused our attention on the analysis of the early stages of human notochord development by highlighting the role of progenitor stem cells involved in the origin of intervertebral discs (IVDs).Eight human fetuses, ranging from 8 up to 21 weeks of gestational age, were obtained from spontaneous abortion or voluntary interruption of gestation. Samples were 10% formalin-fixed, routinely processed, and paraffin-embedded. Five micron-tick paraffin sections were obtained from each sample. Sections were stained with hematoxylin-eosin and PAS stain for a morphological examination. Tissue samples were immunostained with a commercial anti-human CD44 rabbit monoclonal antibody at 1:100 dilution.Immunoreactivity for CD44 was detected in six out of eight notochords examined in this study. Reactivity for CD44 was restricted to progenitor cells giving rise to the nucleus pulposus (NP) of the developing IVDs. Positive cells showed a membranous and/or cytoplasmic immunostaining, no reactivity was observed in the nuclear compartment. CD44 expression was always restricted to IVD precursor cells, whereas cartilage precursors were devoid of labelling.Our study shows, for the first time, that the stem cell marker CD44 selectively marks intervertebral disc progenitor cells, paralleling their differentiation toward a discogenic phenotype. Therefore, our results suggest that CD44 plays a key role in IVD development, allowing its differentiation from surrounding undifferentiated notochordal cells toward a IVD phenotype. Given the role of CD44 in IVD development, we may hypothesize that low CD44 levels might be associated with changes in IVD development and with susceptibility to develop back pain later in life.

L1 cell adhesion molecule (L1CAM) is a glycoprotein characterized by three components: an extracellular region, a transmembrane segment, and a cytoplasmic tail. L1CAM is expressed in multiple human cells, including neurons. The neural cell adhesion molecule L1 has been implicated in a variety of neurologic processes, including neuritogenesis and cerebellar cell migration. The presence of L1CAM on the surface of nerve cells allows the adhesion of neurons among them. Furthermore, when it is bound to itself or to other proteins, L1-CAM induces signals inside the cell. The aim of this work was to study L1CAM expression in the human spinal cord during development, at different gestational ages, through immunohistochemistry.Immunohistochemical analysis for L1CAM was performed in five human spinal cord samples, including three embryos and two fetuses of different gestational ages, ranging from 8 to 12 weeks.L1CAM expression was detected in all 5 spinal cords examined in this study. The adhesion molecule was found in the vast majority of cells. The highest levels of immunoreactivity for L1CAM were detected at the periphery of the developing organs, in the spinal cord zones occupied by sensory and motor fibers. In the alar and basal columns, immunoreactivity for L1CAM was characterized by a reticular pattern, being mainly expressed in axons. Strong reactivity of L1CAM was also found in extracellular vesicles. This extracellular localization might indicate the ability of L1CAM to mediate the transduction of extracellular signals that support axon outgrowth.The high reactivity of L1cam in the axons of developing neurons in the fetal spinal cord confirms previous studies on the ability of L1CAM to promote axon sprouting and branching in the developing nervous system. In this work, a new actor is reported to have a role in the complex field of human spinal cord development: L1CAM, whose expression is highly found in the developing neuronal and glial precursors.

L1 cell adhesion molecule (L1CAM) is a member of the immunoglobulin superfamily of cell adhesion molecules. The present study investigated the expression of L1CAM during the development in the fetal human kidney at different gestational ages, to reach a better knowledge on the role of L1CAM in renal morphogenesis.The immunohistochemical analysis for L1CAM was performed in 24 fetal kidneys of different gestational ages, ranging from 10 to 38 weeks. L1CAM expression was observed in all 24 kidneys examined.Immunoreactivity for L1CAM was restricted to the collecting tubules, of the developing fetal kidneys. Moreover, L1CAM was detected in the ureteric bud tips, near the subcapsular metanephric mesenchymal stem/progenitor cells. L1CAM was also expressed in the collecting tubules undergoing fusion with the distal tubules of the developing nephrons. L1CAM was mainly expressed along the cell membrane. In fetal kidneys in which the renal pelvis was observed, epithelial cells of the renal pelvis showed strong membranous reactivity for L1CAM.Our study shows that L1CAM is expressed in all stages of human kidney nephrogenesis, being restricted to the renal structures derived from the ureteric bud. The expression of L1CAM in the cells of the ureteric bud tips suggests a major role for this adhesion molecule in the induction of metanephric mesenchymal cells to undergo mesenchymal-to-epithelial transition and differentiation into new nephrons. The interindividual variability in L1CAM expression observed in this study might be related to different levels of nephrogenesis, suggesting L1CAM involvement in the fetal programming of adult kidney diseases.

The growing incidence of cancers is pushing oncologists to find out new explanations other than the somatic mutation theory, based on the accumulation of DNA mutations. In particular, the embryo-fetal exposure to an increasing number of environmental factors during gestation might represent a trigger able to influence the susceptibility of the newborn to develop cancer later in life. This idea agrees with the fetal programming theory, also known as the Barker hypothesis. Here the role of insulin-like growth factors, thymosin beta-4, and epigenome are discussed as mediators of cancer in prenatal human development. The role of epigenetic factors that during gestation increase the predisposition to develop cancer and the similarities in the gene expression (like MMP9, OPN, TP53 and CDKN2A) between embryonic development and cancer are key factors. Likewise, maternal obesity might be able to re-program embryo-fetal development with long-term changes, including an increased risk to develop neuroblastoma and acute leukemia. Birth weight alone and birth weight corrected for gestational age are proposed as important variables capable of predicting the vulnerability to develop cancers. According to the findings here reported, we hypothesize that cancer prevention should start during gestation by improving the quality of maternal diet. In conclusion, the Barker hypothesis should be applied to cancer as well. Therefore, the identification of the epigenetic factors of cancer appears mandatory, so that the cancer prevention might start in the womb before birth.

Acyl-CoA-binding protein (ACBP), also known as diazepam binding inhibitor (DBI), is a small phylogenetically conserved protein. This ancestral peptide is multifunctional, performing intracellular activities as ACBP protein or extracellular roles as DBI. Several studies showed its endless facets, including a relevant activity as appetite stimulator and as anabolic factor. High levels of ACBP have been described in erythrocytes, liver, kidney, and gut cells. The aim of this study was to analyze, at immunohistochemical level, the expression of ACBP in fetal human tissues during development, focusing on the developing kidney.Immunohistochemistry for ACBP was performed on 30 human fetal kidneys, from 15 fetuses of gestational age ranging from 13 to 19 weeks. At autopsy, all kidney samples were 10% formalin-fixed, routinely processed and paraffin-embedded. Five micron-thick paraffin sections were stained with Hematoxylin and Eosin and PAS stain for a morphological examination.ACBP was detected in all 30 kidneys analyzed in this study. No significant changes in ACBP expression were observed at different gestational ages. Immunostaining for ACBP was restricted to the epithelium covering the renal pelvis, the papillae, the collecting tubules, and the proximal and distal tubules. On the other hand, medullary regions and in the metanephric mesenchymal stem/progenitor cells did not show any reactivity for ACBP.According to our findings, ACBP should be considered as a new player in the complex field of human nephrogenesis, given that it was detected in all fetal kidneys immunostained. Its preferential localization in the renal structures derived from the Wolf duct, such as pelvis epithelium and collecting ducts, suggests a major role for ACBP in the induction of the metanephric mesenchymal cells toward the differentiation into glomerular structures. ACBP expression in proximal and distal tubules, two structures originating from the metanephric mesenchyme, indicates a further role of this protein in nephron development. In conclusion, ACBP should be added to the multiple molecules involved in human nephrogenesis.

Previous studies have confirmed the key mechanism by which SARS-CoV-2 enters human cells. It is well established that ACE2 is the receptor that can mark the beginning of the infection. In light of this, the organs that express higher levels of ACE2 are generally considered at higher risk, while those with lower levels should be somehow more protected. This - if related to the scarcity of ace2-expressing cells in the brain - seems to contrast with the presence of a variety of neurological symptoms that follow infection with ace2. The aim of this work was to analyze ACE2 expression in the human brain, focusing on the choroid plexuses.Twenty brain samples were obtained at autopsy from ten human fetuses and from ten adult subjects. All samples were selected to contain the choroid plexus. Specimens were fixed in 10% formalin, routinely processed and paraffin embedded. 5-micron sections were stained with Hematoxylin and Eosin (HE) and immunostained with a commercial anti-human ACE2 rabbit monoclonal antibody at 1:100 dilution.We analyzed 20 samples by immunohistochemistry, and we noted that, as far as fetal samples are concerned, a strong reactivity for ACE2 was detected in the myxoid stroma of the choroid plexuses and in the endothelial cells in fetuses. The complete absence of the ACE2 marker was detected in epithelial cells, neurons and glial cells of the cerebral cortex, both in fetuses and in adults. Whereas a strong but selective reactivity for ACE2 was also detected in adult choroid plexuses, mainly localized in the endothelial cells of the choroid capillaries.Our study shows a strong expression of ACE in the fetal and adult brain choroid plexuses. This new histopathological finding may clarify the susceptibility of the human brain to SARS-COV-2 infection. Our data indicate the choroid plexus as the entry gate of virus for in the human brain; therefore, the entrance of SARS-CoV-2 into the cerebrospinal fluid through the choroid plexuses might represent the mechanism utilized by this coronavirus to cause direct injury to brain cells.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare new syndrome occurring after the ChAdOx1 nCoV-19 vaccine immunization. Patients with VITT are characterized by a variable clinical presentation, likewise also the outcome of these patients is very variable. Here we report the lung ultrastructural findings in the course of VITT of a 58-year-old male patient. Alveoli were mainly dilated, irregular in shape, and occupied by a reticular network of fibrin, while interalveolar septa appeared thickened. The proliferation of small capillaries gave rise to plexiform structures and pulmonary capillary hemangiomatosis-like features. Near the alveoli occupied by a dense fibrin network, the medium-sized arteries showed a modified wall and an intraluminal thrombus. This scenario looks quite similar to that found during COVID-19, where the lungs suffer from the attack of the antigen-antibodies complexes and the virus respectively. In both diseases, the final outcome is a severe inflammation, activation of the haemostatic system and fibrinolysis.

The ongoing Coronavirus pandemic (COVID-19) showed similar characteristics with the severe acute respiratory syndrome (SARS). In the most compromised cases, COVID-19 infection leads to death due to severe respiratory complications. COVID-19-related acute respiratory distress syndrome (ARDS) is the primary cause of death in these patients. In the present study, we show an ultrastructural analysis on the lungs of a patient affected by COVID-19.Lung specimens obtained at autopsy from a 63-years old patient affected by COVID-19 were fixed in 1% paraformaldehyde. Slices of 300 µm thickness were dehydrated and dried by Critical Point Drying in CO2. Slices were covered with a conductive gold film approximately 30 nm thick and observed at a Zeiss Sigma 300 SEM FEG in the secondary electron (SE) and backscattered electron (BSE) modes. As case control a lung biopsy from a 60-year-old man was considered.At low power in all COVID-19 lung specimens severe changes in the pulmonary architecture were found, due to the collapse of air spaces. Moreover, alveolar cavities were covered by large membranes. At high power, alveolar membranes showed a fibrillar structure, suggestive of a loose network of fibrin. It has been also found that intra-alveolar red blood cells were frequently present in the alveolar spaces, surrounded by a reticular fibrin network, suggestive for fibrin-hemorrhagic alveolitis. Alveolar changes were constantly associated with pathological features related to the pulmonary vessels. Vascular changes were prominent, including endothelial damage and thrombosis of large pulmonary vessels. Fibrinous microthrombi were frequently detected in the inter-alveolar septal capillaries. In addition, it has been frequently detected capillary proliferation in the alveolar septa with finding suggestive for intussusceptive neo-angiogenesis.In conclusion, our electron microscopy analysis showed that COVID-19-related lung disease is characterized by a substantial architectural distortion, with the interactions between alveolar and vascular changes. Intra-alveolar hyaline membranes are associated with macro- and micro-thrombotic angiopathy, ending with capillary proliferation. The new blood vessel formation originates from the septa and extends into the surrounding parenchyma. Our findings confirm previous reports on the specificity of the multiple and complex morphological pattern typical, and apparently specific, of COVID-19-related lung disease.

The risk stratification of young adults between subjects who will develop a mild form of atherosclerosis and subjects who will undergo a severe disease remains inaccurate. In the eighties of the previous century, David JP Barker has demonstrated the relationship between fetal conditions and occurrence of pathologies in adulthood. In this paper, the multiple evidence that might explain the increased susceptibility to severe forms of atherosclerosis, including stroke and cardiac infarct, in subjects who underwent intrauterine growth restriction (IUGR) will be analyzed. Specifically, we will review those inter-connected data indicating an association between a low weight at birth and an adult phenotype which might favor a severe outcome of atherosclerosis. Young and adult subjects born too small (IUGR) or too early (pre-terms) might represent a subgroup of "at risk subjects", more susceptible toward severe forms of atherosclerosis. Given that low birth weight (LBW) may be considered a surrogate of IUGR, this phenotypic feature could be considered among those indispensable clinical data collected in every patient presenting with atherosclerosis, irrespectively of age. According to the hypothesis that structural arterial changes might represent the link between LBW and susceptibility to atherosclerosis later in life, we suggest that the prevention of atherosclerosis should begin at birth. Regenerative and physiological substances such as thymosin Beta-4 could be challenged for a new "arterial regenerative medicine" in the perinatal period. The goal of this new approach should be the reinforcement of the structure of the arterial wall, allowing LBW newborns to avoid the most severe complications of atherosclerosis later in life: a dream that our research could contribute to bringing to life.

Liver injury has been reported in patients with COVID-19. This condition is characterized by severe outcome and could be related with the ability of SARS-CoV-2 to activate cytotoxic T cells. The purpose of this study is to show the histological and scanning electron microscopy features of liver involvement in COVID-19 to characterize the liver changes caused by the activation of multiple molecular pathways following this infection.Liver biopsies from 4 patients (3 post-mortems and 1 in vivo) with COVID-19 were analyzed with histology and by scanning electron microscopy.The liver changes showed significant heterogeneity. The first case showed ground glass hepatocytes and scattered fibrin aggregates in the sinusoidal lumen. The second evidenced intra-sinusoidal thrombi. The third was characterized by sinusoidal dilatation, atrophy of hepatocytes, Disse's spaces dilatation and intra-sinusoidal aggregates of fibrin and red blood cells. The fourth case exhibited diffuse fibrin aggregates in the dilated Disse spaces and microthrombi in the sinusoidal lumen.In COVID-19-related liver injury, a large spectrum of pathological changes was observed. The most peculiar features were very mild inflammation, intra-sinusoidal changes, including sinusoidal dilatation, thrombotic sinusoiditis and diffuse intra-sinusoidal fibrin deposition. These findings suggested that a thrombotic sinusoiditis followed by a local diffuse intra-vascular (intra-sinusoidal) coagulation could be the typical features of the SARS-CoV-2-related liver injury.

The risk stratification of young adults between subjects who will develop a mild form COVID-19 and subjects who will undergo a severe disease remains inaccurate. In this review, we propose that the Barker hypothesis might explain the increased susceptibility to severe forms of COVID-19 in subjects who underwent intrauterine growth restriction (IUGR). In this paper evidence indicating an association between a low birth weight and an adult phenotype which might favor a severe outcome of SARS-CoV-2 infection are presented: lower lung functional capacity; increased respiratory morbidity; changes in fibrinogen and Factor VII serum levels and dysregulation of the hemostasis and thrombosis system; acquisition of a pro-thrombotic phenotype; low nephron number, with decreased ability to sustain renal function and increased renal morbidity; heart remodeling, with a less efficient cardiac function; endothelial dysfunction, a risk factor for the insurgence of the multiple organ failure; remodeling of arteries, with changes in the elastic properties of the arterial wall, predisposing to the insurgence and progression of atherosclerosis; dysfunction of the innate immune system, a risk factor for immune diseases in adulthood. These data suggest that young and adult subjects born too small (IUGR) or too early (pre-terms) might represent a subgroup of "at risk subjects", more susceptible toward severe forms of COVID-19. Given that LBW may be considered a surrogate of IUGR, this phenotypic marker should be included among the indispensable clinical data collected in every patient presenting with SARS-COV-2 infection, irrespectively of his/her age.

Vaccine-induced immune thrombocytopenia (VITT) is a new syndrome occurring primarily in healthy young adults, with a female predominance, after receiving the first dose of ChAdOx1 nCoV-19 vaccine. We describe VITT syndrome characterized by severe thrombosis and thrombocytopenia found in our patient, with fatal outcome.A 58-year-old man, after 13 days from the first administration of ChAdOx1 nCoV-19 vaccine (AstraZeneca), presented with abdominal pain, diarrhea and vomitus. Laboratory tests revealed a severe thrombocytopenia, low fibrinogen serum levels and marked increase of D-dimer serum levels. The patient quickly developed a multiple organ failure, till death, three days after the hospital admission.At histology, in the lungs, interalveolar septa appeared thickened with microthrombi in the capillaries and veins. Interalveolar septa appeared thickened and showed vascular proliferation. Thrombi were detected in the capillaries of glomerular tufts. In the hearth, thrombi were observed in veins and capillaries. In the liver, voluminous fibrin thrombi were diffusely observed in the branches of the portal vein. Microthrombi were also found in the vasa vasorum of the wall of abdominal aorta. In the brain, microthrombi were observed in the capillaries of the choroid plexuses. Diffuse hemorrhagic necrosis was observed in the intestinal wall with marked congestion of the venous vessels.In our patient, the majority of data necessary for a VITT final diagnosis were present: thrombocytopenia and thrombosis in pulmonary, portal, hepatic, renal and mesenteric veins, associated with a marked increase of D-dimer serum levels. The finding of cerebral thrombosis in choroid plexuses, is a new finding in VITT. These features are suggestive for a very aggressive form of VITT.

Acute respiratory distress syndrome (ARDS) is characterized by quantitative and qualitative changes in surfactant composition, leading to surfactant dysregulation with alveolar collapse and acute respiratory hypoxic failure. Recently, surfactant has been hypothesized to play a relevant role in COVID-19, representing a strong defender against SARS-CoV-2 infection. The aim of our work was the study of immunohistochemical surfactant expression in the lungs of patients died following SARS-CoV-2 ARDS, in order to shed light on a possible therapeutic surfactant administration.We investigated four patients who died due to ARDS following SARS-COV-2 infection and four patients submitted to lung biopsy, in the absence of SARS-CoV-2 infection. In all 8 cases, lung specimens were immunostained with anti-surfactant protein A (SP-A) and B (SP-B).In control subjects, reactivity for SP-B was restricted to type II alveolar cells. Immunostaining for SP-A was observed on the surface of alveolar spaces. In the COVID-19 positive lungs, immunoreactivity for SP-B was similar to that observed in control lungs; SP-A was strongly expressed along the alveolar wall. Moreover, dense aggregates of SP-A positive material were observed in the alveolar spaces.Our immunohistochemical data show the dysregulation of surfactant production in COVID-19 patients, particularly regarding SP-A expression. The increased presence of SP-A in condensed masses inside alveolar spaces could invalidate the therapeutic efficacy of the treatment with exogenous surfactant.

Multiple epidemiological studies have suggested that industrialization and progressive urbanization should be considered one of the main factors responsible for the rising of atherosclerosis in the developing world. In this scenario, the role of trace metals in the insurgence and progression of atherosclerosis has not been clarified yet. In this paper, the specific role of selected trace elements (magnesium, zinc, selenium, iron, copper, phosphorus, and calcium) is described by focusing on the atherosclerotic prevention and pathogenesis plaque. For each element, the following data are reported: daily intake, serum levels, intra/extracellular distribution, major roles in physiology, main effects of high and low levels, specific roles in atherosclerosis, possible interactions with other trace elements, and possible influences on plaque development. For each trace element, the correlations between its levels and clinical severity and outcome of COVID-19 are discussed. Moreover, the role of matrix metalloproteinases, a family of zinc-dependent endopeptidases, as a new medical therapeutical approach to atherosclerosis is discussed. Data suggest that trace element status may influence both atherosclerosis insurgence and plaque evolution toward a stable or an unstable status. However, significant variability in the action of these traces is evident: some - including magnesium, zinc, and selenium - may have a protective role, whereas others, including iron and copper, probably have a multi-faceted and more complex role in the pathogenesis of the atherosclerotic plaque. Finally, calcium and phosphorus are implicated in the calcification of atherosclerotic plaques and in the progression of the plaque toward rupture and severe clinical complications. In particular, the role of calcium is debated. Focusing on the COVID-19 pandemia, optimized magnesium and zinc levels are indicated as important protective tools against a severe clinical course of the disease, often related to the ability of SARS-CoV-2 to cause a systemic inflammatory response, able to transform a stable plaque into an unstable one, with severe clinical complications.

Continuous Wave gyrotrons are the key elements for Electron Cyclotron Resonance Heating and Current Drive (ECRH&CD) in present fusion experiments and future fusion reactors. In the frame of the EUROfusion activities, a 170 GHz, 2 MW short-pulse (∼ 1 ms), water-cooled coaxial gyrotron, already tested at Karlsruhe Institute of Technology (KIT), is being upgraded for operation at longer pulses (∼ 100–1000 ms). Here we use the MUlti-physiCs tool for the integrated simulation of the CAvity (MUCCA), recently developed in collaboration between Politecnico di Torino and KIT, to analyze the evolution of the operating condition of the coaxial gyrotron cavity, self-consistently coupling thermal-hydraulic, thermo-mechanical and electro-dynamic models. The main results are presented in terms of evolution of temperature, heat load and deformation of the heated surface of the resonator and of the coaxial insert during the first few seconds of operation. We show that the system evolves towards stable operating conditions (no beam loss), with a peak temperature strongly dependent on the cooling configuration, where a large room for the improvement of the current cavity cooling design is found.

The present work exposes the 3D steady state thermal hydraulic (TH) analysis of the Irregular Sector number 3 (IrS#3) of the ITER Vacuum Vessel (VV), including the Irregular Field Joints (IrFJ) by means of a commercial CFD (Computational Fluid Dynamics) code. The geometry of the IrS#3 has been simplified and healed in order to be suitable for CFD analysis. The simplified geometry has been meshed and converted to a polyhedral cell based mesh so as to enhance accuracy and calculation stability. Nuclear heat deposition ( H ) from the latest C Lite model [1] has been implemented through several User Defined Functions (UDF). Water coolant and stainless steel shell are solved together as a steady state conjugate heat transfer problem in order to assess the impact of the nuclear heat deposition on the IrS#3 cooling scheme. Hence, the IrS#3 is simulated as a whole, without splitting the domain. Results show the total IrS#3 pressure drop as well as the flow and temperature distribution all over the IrS#3. Moreover, the heat transfer coefficient ( h ) has been calculated at the fluid-solid interface. Velocity magnitude in the water coolant has an average value of 0.10 m/s and mass flow rate distribution is 11% and 89% respectively for Inboard and Outboard. The pressure drop, mainly concentrated at inlet and outlet ducts, is of 77.4 kPa. The average h is of 5 690 W/(m 2 K), way above the design limit of 500 W/(m 2 K). The fluid temperature stays at an average value of 101.7 °C. The results obtained have a significant importance regarding design and safety and give a valuable insight on the current cooling scheme and system behavior for the IrS#3 of the ITER VV. This follows a previous work presenting the methodology and the results of a 3D TH analysis of the Irregular Sector number 2 (IrS#2) of the ITER Vacuum Vessel (VV) by means of CFD [2].

In the frame of the TCV Tokamak upgrade, two 84/126 GHz/2 s dual frequency Gyrotrons designed by SPC and KIT and manufactured by THALES MSI will be added to the existing EC-System. The first unit has been delivered to EPFL-SPC and tested. In the commissionning configuration, a matching optics unit (MOU) is connected to the gyrotron window. The RF is then coupled to the HE11 mode of a 63.5mm corrugated waveguide and dissipated in a load procured by CNR after 4m of waveguides and 2 miter bends. Owing to the flexible triode gun design giving the possibility to adjust the pitch angle parameter, the specifications were met at both frequencies. At 84 GHz (TE17,5 mode), a power of 0.930MW was measured in the calorimeter, with a pulse duration of 1.1s. At the high frequency (126 GHz, TE26,7 mode), a power of 1.04 MW was reached for a pulse length of 0.5 s. Accounting for the load reflection and the ohmic losses in the various subcomponents of the transmission line and the tube, it is estimated that the output power at the gyrotron window is in excess of 1MW at both frequencies, with an electronic efficiency of 32% and 34% at 84 GHz and 126 GHz respectively. The gyrotron behaviour is remarkably robust and reproducible, suggesting that the ongoing implementation in the gyrotron control and protection system of an already tested novel collector sweeping modulation scheme will permit the straightforward extension of the pulse length to 2s.

An iterative procedure is described, which models the influence of the thermal expansion of the gyrotron cavity on the expected gyrotron performance. It is a multi-physics simulation method, which involves electrodynamic, thermohydraulic, and thermo-mechanical simulations. The method is applied to the first European 170 GHz, 1 MW CW prototype gyrotron for ITER. According to calculations, a performance reduction of ∼15% is expected at nominal operating parameters because of the simulated thermal expansion of the cavity. An alternative operating point to mitigate this effect is proposed.

Fusion for Energy (F4E) is involved in a relevant number of activities in the area of electromagnetic analysis in support of ITER general design and EU in-kind procurement. In particular several ITER components (vacuum vessel, blanket shield modules and first wall panels, test blanket modules, ICRH antenna) are being analyzed from the electromagnetic point of view. In this paper we give an updated description of our main activities, highlighting the main assumptions, objectives, results and conclusions. The plasma instabilities we consider, typically disruptions and VDEs, can be both toroidally symmetric and asymmetric. This implies that, depending on the specific component and loading conditions, FE models we use span from a sector of 10 up to 360° of the ITER machine. The techniques for simulating the electromagnetic phenomena involved in a disruption and the postprocessing of the results to obtain the loads acting on the structures are described. Finally we summarize the typical loads applied to different components and give a critical view of the results.

The EU gyrotron for the ITER Electron Cyclotron heating system has been developed in coordinated efforts from several EU institutions and under the supervision of ITER Organization Central Team. This paper presents the main experimental results from the main prototyping and qualification activities aiming to demonstrate compliance with the ITER specifications and reduce the technical risks during the series production phase.

Several different types of windings can be adopted to generate the magnetic field required for the EDIPO (Efda DIPOle) test facility. Apart from the so-calledcos thetas winding configuration, which is most compacted but hardly applicable for large, rectangular apertures, other configurations have been studied within the framework of the EDIPO conceptual design. These configurations, bulkier than the cos thetas winding, offer advantages in the manufacturing as well as in the peak stresses and insulation reliability. The aim of this paper is to review the results of these studies considering alternatives to the cos thetas winding that generate the desired dipole magnetic field by means of planar (1) or tilted head (2) racetrack coils sets. The comparison among the different winding configurations is carried out on the basis of different cost indexes (such as the winding volume, peak field, magnetic energy etc.) as well as for different winding engineering current densities.

A 12.5 T superconducting dipole magnet (European DIPOle, EDIPO) has been designed by EFDA and it is now being procured within the framework of the European Fusion Programme in order to be installed in CRPP-PSI. This saddle-shaped magnet is designed to reach 12.5 T in a 100 times 150 mm rectangular bore over a length of about 1.5 m in order to test full size conductor samples that shall be produced during the ITER magnets procurement. The magnet uses Cable In Conduit Conductor (CICC) technology and the cables are made of high Jc (about 2300 A/mm2 at 4.2 K, 12 T) superconducting strands. In this paper the main magnet parameters are given together with the key supporting electromagnetic, mechanical and thermal analyses. An update on the general status of the procurement of the strand, conductors, dipole magnet and facility is also given together with the key results of the on-going supporting R&D.

In large, cabled superconductors, a non-negligible level of current unbalance among the strands is unavoidable in dc operation due to non-homogeneous contact resistance distribution at the electrical connections. When the overloaded strands saturate their current carrying capability and start to develop current sharing voltage at the high field section, the excess current must be transferred to less loaded strands. The inter-strand current re-distribution takes likely place at the electrical connections, where the inter-strand resistance is lower. Two samples of electrical termination, made of large cable-in-conduit conductors, were formerly prepared and tested for contact resistance distribution at CRPP. One of these samples is now re-arranged to measure the inter-strand resistance in different combination. A discussion of the results allows ruling out speculations about the impact of current re-distribution effects on the voltage-current and voltage-temperature characteristics in short length conductor test.

The first detailed Computational Fluid Dynamics (CFD) analysis of the FW06 panel of the ITER shielding blanket is presented in two companion papers. In this Part I we introduce the problem, define the model together with its input and discuss the results with particular reference to the hydraulics of the water coolant. The pressure drop across the panel is computed, together with the distribution of the flow among the different channels. Different design options are studied, with particular reference to the minimization of stagnation/recirculation regions.

The computational fluid dynamics (CFD) analysis of the FW06 panel of the ITER shielding blanket is presented in two companion papers. In this Part II we concentrate on the thermal-hydraulics of the water coolant, driven by the nuclear volumetric and plasma surface heat loads discussed in Part I. Both the detailed steady state analysis of a single cooling channel and the coarse transient analysis of the whole panel are considered. The compatibility of the hot spots with the maximum recommended temperatures for the different materials is confirmed. The heat transfer coefficient between coolant and walls is obtained post-processing the results of the simulation and compared with the results of available correlations, which may be used for simpler analyses: in the fully developed flow regions of the cooling pipes, it turns out to be well approximated by the Sieder–Tate correlation. The operation margin with respect to the critical heat flux is also computed and turns out to be sufficiently large compared with the design limit.

Several prototype Cable‐In‐Conduit‐Conductors (CICC) for the superconducting EDIPO (Efda DIPOle) revealed a degradation of their critical current (Ic) increasing with each loading cycle. The strong Lorentz‐forces during operation in combination with the limited support of the single strands against these forces are thought to be the cause of the permanent degradation of the brittle Nb3Sn superconductor from which the multi‐stranded CICC are made. In summer 2006 EFDA started to explore the possibility to remedy the Ic degradation by solder‐filling the conductor in order to mechanically stabilize the twisted‐strand cable inside the conduit. This solution was not considered as the main one, but as an emergency solution to be applied to the completed magnet, should every other option fail. The solder‐filling approach was previously applied with success in some cases. Some issues, however, needed to be clarified before this solution could be proposed for the EDIPO project. The most important among them are the choice of solder material, details of the solder filling process, and the thermo‐mechanical implications of a solder‐filled, high‐field, high‐current cable. This work, being reported here, made use not only of simulation but also of experiments, such as the mechanical testing of solder filled cables at cryogenic temperatures.

The EFDA dipole (EDIPO) is a superconducting magnet made of a pair saddle-shaped winding packs enclosed in a circular iron yoke which, in turn, is contained inside an austenitic steel cylinder. In this paper the key electromechanical features of the dipole are presented. As far as the static analysis is concerned, the electromagnetic and mechanical behavior of the whole system has been analyzed by means of finite element models, in order to evaluate, in particular, the peak field on the cables, the stress limit in the jacket and the shear stresses in the insulation. As far as the transient analysis is concerned, the system behavior during a current dump has been simulated by means of a coupled electromagnetic-circuit model that takes into account the non linearity of the ferromagnetic material and the reaction field due to the eddy currents in the steel cylinder. Another important element in the AC analysis consists in the assessment of the conductor losses during AC operation, since they provide the heat loads to be evacuated by the cooling system. The results of this last issue are also presented.

In this paper we illustrate the implementation of an actual MANET demonstrator, based on off-the-shelf PDA devices with IEEE 802.11b wireless connectivity, tested on real-time applications. The most critical aspect affecting performances, in our opinion, is related to create a network where connectivity among nodes is as stable as possible. We implemented an enhanced version of the AODV protocol by embedding routing policies in order to choose routes based on link stability evaluation and show the effectiveness of this approach by means of simulations. Finally we describe the demonstration phases in a mixed indoor/outdoor environment.

In this paper, an original algorithm to solve multiobjective design problems, which makes use of a neural network (NN) inversion method, is presented. The proposed approach allows us to explore the solutions directly in the objectives space, rather than in the parameters space, with a great saving of computation time in the reconstruction of the Pareto front. A multilayer perceptron NN is first trained to solve the analysis design problem. The inversion of the neural model allows us to obtain the design parameters, starting from the desired requirements on all the conflicting multiple objectives. The performance of the method is demonstrated by its application to the design of a high-field superconducting dipole magnet, where a tradeoff between the superconductors volumes is required in order to obtain a prescribed magnetic field value in the dipole axis

All the ITER superconductors are tested as short length samples in the SULTAN test facility at CRPP. Twenty-four TF conductor samples with small layout variations were tested since February 2007 with the aim of verifying the design and qualification of the manufacturers. The sample assembly and the measurement techniques at CRPP are discussed. Starting in 2010, another test facility for ITER conductors, named EDIPO, will be operating at CRPP to share with SULTAN the load of the samples for the acceptance tests during the construction of ITER.

CRPP has been selected to host the EDIPO test facility for the quality control tests of the ITER conductors. The new facility will be erected next to the existing SULTAN test facility at CRPP (Villigen) in Switzerland and will share the same cryo-plant. Operation of the two facilities is planned in parallel starting 2009. The new facility is designed to test short length samples built to the same specification as for SULTAN. EFDA procures 17 tons superconducting winding under industrial contract that will be delivered to CRPP in late 2008. The preparatory work at CRPP includes the design and procurement of several items as well as the final assembly and commissioning of the facility. An overview and the progress are reported, with focus on the main components: the vacuum vessel, the superconducting transformer and sample holder unit, the cryogenic cooling loop, the power supply and quench protection system, the HTS current leads and the magnetic screen.