A high-density and high-confinement tokamak plasma regime for fusion energy.

The tokamak approach, utilizing a toroidal magnetic field configuration to confine a hot plasma, is one of the most promising designs for developing reactors that can exploit nuclear fusion to generate electrical energy1,2. To reach the goal of an economical reactor, most tokamak reactor designs3-10 simultaneously require reaching a plasma line-averaged density above an empirical limit-the so-called Greenwald density11-and attaining an energy confinement quality better than the standard high-confinement mode12,13. However, such an operating regime has never been verified in experiments. In addition, a long-standing challenge in the high-confinement mode has been the compatibility between a high-performance core and avoiding large, transient edge perturbations that can cause very high heat loads on the plasma-facing-components in tokamaks. Here we report the demonstration of stable tokamak plasmas with a line-averaged density approximately 20% above the Greenwald density and an energy confinement quality of approximately 50% better than the standard high-confinement mode, which was realized by taking advantage of the enhanced suppression of turbulent transport granted by high density-gradients in the high-poloidal-beta scenario14,15. Furthermore, our experimental results show an integration of very low edge transient perturbations with the high normalized density and confinement core. The operating regime we report supports some critical requirements in many fusion reactor designs all over the world and opens a potential avenue to an operating point for producing economically attractive fusion energy.

Experimental Validation of a Kinetic Ballooning Mode in High-Performance High-Bootstrap Current Fraction Fusion Plasmas.

We report the observation of a set of coherent high frequency electromagnetic fluctuations that leads to a turbulence induced self-regulating phenomenon in the DIII-D high bootstrap current fraction plasma. The fluctuations have frequency of 130-220 kHz, the poloidal wavelength and phase velocity are 16-30 m^{-1} and ∼30 km/s, respectively, in the outboard midplane with the estimated toroidal mode number n∼5-9. The fluctuations are located in the internal transport barrier (ITB) region at large radius and are experimentally validated to be kinetic ballooning modes (KBM). Quasilinear estimation predicts the KBM to be able to drive experimental particle flux and non-negligible thermal flux, suggesting its significant role in regulating the ITB saturation.

Third-trimester ultrasound for antenatal diagnosis of placenta accreta spectrum in women with placenta previa: results from the ADoPAD study.

OBJECTIVE: To evaluate the performance of third-trimester ultrasound for the diagnosis of clinically significant placenta accreta spectrum disorder (PAS) in women with low-lying placenta or placenta previa. METHODS: This was a prospective multicenter study of pregnant women aged ≥ 18 years who were diagnosed with low-lying placenta (< 20 mm from the internal cervical os) or placenta previa (covering the internal cervical os) on ultrasound at ≥ 26 + 0 weeks' gestation, between October 2014 and January 2019. Ultrasound suspicion of PAS was raised in the presence of at least one of these signs on grayscale ultrasound: (1) obliteration of the hypoechogenic space between the uterus and the placenta; (2) interruption of the hyperechogenic interface between the uterine serosa and the bladder wall; (3) abnormal placental lacunae. Histopathological examinations were performed according to a predefined protocol, with pathologists blinded to the ultrasound findings. To assess the ability of ultrasound to detect clinically significant PAS, a composite outcome comprising the need for active management at delivery and histopathological confirmation of PAS was considered the reference standard. PAS was considered to be clinically significant if, in addition to histological confirmation, at least one of these procedures was carried out after delivery: use of hemostatic intrauterine balloon, compressive uterine suture, peripartum hysterectomy, uterine/hypogastric artery ligation or uterine artery embolization. The diagnostic performance of each ultrasound sign for clinically significant PAS was evaluated in all women and in the subgroup who had at least one previous Cesarean section and anterior placenta. Post-test probability was assessed using Fagan nomograms. RESULTS: A total of 568 women underwent transabdominal and transvaginal ultrasound examinations during the study period. Of these, 95 delivered in local hospitals, and placental pathology according to the study protocol was therefore not available. Among the 473 women for whom placental pathology was available, clinically significant PAS was diagnosed in 99 (21%), comprising 36 cases of placenta accreta, 19 of placenta increta and 44 of placenta percreta. The median gestational age at the time of ultrasound assessment was 31.4 (interquartile range, 28.6-34.4) weeks. A normal hypoechogenic space between the uterus and the placenta reduced the post-test probability of clinically significant PAS from 21% to 5% in women with low-lying placenta or placenta previa in the third trimester of pregnancy and from 62% to 9% in the subgroup with previous Cesarean section and anterior placenta. The absence of placental lacunae reduced the post-test probability of clinically significant PAS from 21% to 9% in women with low-lying placenta or placenta previa in the third trimester of pregnancy and from 62% to 36% in the subgroup with previous Cesarean section and anterior placenta. When abnormal placental lacunae were seen on ultrasound, the post-test probability of clinically significant PAS increased from 21% to 59% in the whole cohort and from 62% to 78% in the subgroup with previous Cesarean section and anterior placenta. An interrupted hyperechogenic interface between the uterine serosa and bladder wall increased the post-test probability for clinically significant PAS from 21% to 85% in women with low-lying placenta or placenta previa and from 62% to 88% in the subgroup with previous Cesarean section and anterior placenta. When all three sonographic markers were present, the post-test probability for clinically significant PAS increased from 21% to 89% in the whole cohort and from 62% to 92% in the subgroup with previous Cesarean section and anterior placenta. CONCLUSIONS: Grayscale ultrasound has good diagnostic performance to identify pregnancies at low risk of PAS in a high-risk population of women with low-lying placenta or placenta previa. Ultrasound may be safely used to guide management decisions and concentrate resources on patients with higher risk of clinically significant PAS. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Role of Microtearing Turbulence in DIII-D High Bootstrap Current Fraction Plasmas.

We report on the first direct comparisons of microtearing turbulence simulations to experimental measurements in a representative high bootstrap current fraction (f_{BS}) plasma. Previous studies of high f_{BS} plasmas carried out in DIII-D with large radius internal transport barriers (ITBs) have found that, while the ion energy transport is accurately reproduced by neoclassical theory, the electron transport remains anomalous and not well described by existing quasilinear transport models. A key feature of these plasmas is the large value of the normalized pressure gradient, which is shown to completely stabilize conventional drift-wave and kinetic ballooning mode instabilities in the ITB, but destabilizes the microtearing mode. Nonlinear gyrokinetic simulations of the ITB region performed with the cgyro code demonstrate that the microtearing modes are robustly unstable and capable of driving electron energy transport levels comparable to experimental levels for input parameters consistent with the experimental measurements. These simulations uniformly predict that the microtearing mode fluctuation and flux spectra extend to significantly shorter wavelengths than the range of linear instability, representing significantly different nonlinear dynamics and saturation mechanisms than conventional drift-wave turbulence, which is also consistent with the fundamental tearing nature of the instability. The predicted transport levels are found to be most sensitive to the magnetic shear, rather than the temperature gradients more typically identified as driving turbulent plasma transport.

Accuracy of ultrasound in antenatal diagnosis of placental attachment disorders.

OBJECTIVES: To evaluate the accuracy of ultrasound in the diagnosis of placenta accreta and its variants, and to assess the impact of prenatal diagnosis in our population. METHODS: A total of 314 women with placenta previa were enrolled prospectively and underwent transabdominal and transvaginal ultrasound examinations. An ultrasound diagnosis (grayscale and color/power Doppler) of placental attachment disorder (PAD) was based on the detection of at least two of the following ('two-criteria system'): loss/irregularity of the retroplacental clear zone, thinning/interruption of the uterine serosa-bladder wall interface, turbulent placental lacunae with high velocity flow, myometrial thickness < 1 mm, increased vascularity of the uterine serosa-bladder wall interface, loss of vascular arch parallel to the basal plate and/or irregular intraplacental vascularization. Definitive diagnosis was made at delivery by Cesarean section. Maternal outcome in cases diagnosed antenatally was compared with that in cases diagnosed at delivery. RESULTS: There were 37/314 cases of PAD (29 anterior and eight posterior). The two-criteria system identified 30 cases of placenta accreta, providing a sensitivity of 81.1% and specificity of 98.9%. When anterior and posterior placentae were considered separately, the detection rates of PAD were 89.7 and 50.0%, respectIvely. Maternal outcome was better in women with prenatal diagnosis of PAD, as seen by less blood loss and shorter hospitalization. CONCLUSIONS: Our data confirmed that grayscale and color Doppler ultrasound have good performance in the diagnosis of PAD and that prenatal diagnosis improves maternal outcome. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Dual inhibition of survivin and MAOA synergistically impairs growth of PTEN-negative prostate cancer.

BACKGROUND: Survivin and monoamine oxidase A (MAOA) levels are elevated in prostate cancer (PCa) compared to normal prostate glands. However, the relationship between survivin and MAOA in PCa is unclear. METHODS: We examined MAOA expression in the prostate lobes of a conditional PTEN-deficient mouse model mirroring human PCa, with or without survivin knockout. We also silenced one gene at a time and examined the expression of the other. We further evaluated the combination of MAOA inhibitors and survivin suppressants on the growth, viability, migration and invasion of PCa cells. RESULTS: Survivin and MAOA levels are both increased in clinical PCa tissues and significantly associated with patients' survival. Survivin depletion delayed MAOA increase during PCa progression, and silencing MAOA decreased survivin expression. The combination of MAOA inhibitors and the survivin suppressants (YM155 and SC144) showed significant synergy on the inhibition of PCa cell growth, migration and invasion with concomitant decrease in survivin and MMP-9 levels. CONCLUSIONS: There is a positive feedback loop between survivin and MAOA expression in PCa. Considering that survivin suppressants and MAOA inhibitors are currently available in clinical trials and clinical use, their synergistic effects in PCa support a rapid translation of this combination to clinical practice.

Access to a new plasma edge state with high density and pressures using the quiescent H mode.

A path to a new high performance regime has been discovered in tokamaks that could improve the attractiveness of a fusion reactor. Experiments on DIII-D using a quiescent H-mode edge have navigated a valley of improved edge peeling-ballooning stability that opens up with strong plasma shaping at high density, leading to a doubling of the edge pressure over the standard H mode with edge localized modes at these parameters. The thermal energy confinement time increases as a result of both the increased pedestal height and improvements in the core transport and reduced low-k turbulence. Calculations of the pedestal height and width as a function of density using constraints imposed by peeling-ballooning and kinetic-ballooning theory are in quantitative agreement with the measurements.

Synthesis of esters of androgens with unsaturated fatty acids for androgen requiring therapy.

Androgens' metabolism and activity are gaining a more and more important role in human physiology particularly referring to aging and to neurodegenerative diseases. Androgen treatment is often required for long-lasting disorders. In order to improve their duration and effects, androgens can be administered as esters of carboxylic acids. The novelty of our research is the use of esters of androgens with specific unsaturated fatty acids, in order to reduce possible side effects particularly related to chronic pathologies with altered lipid homeostasis such as X-linked adrenoleukodystrophy and cardiovascular disorders. Thus the esters of the main androgenic substances testosterone, dihydrotestosterone (DHT) and their metabolite 5α-androstan-3α,17ß-diol were chemically obtained by coupling with different unsaturated fatty acids. To this aim, fatty acids with various degree of unsaturation and belonging to different series were selected. Specifically, oleic acid (18:1, n-9), linoleic acid (18:2, n-6), and the n-3 fatty acids, α-linolenic acid (18:3), eicosapentaenoic acid (EPA, 20:5), and docosahexaenoic acid (DHA, 22:6) were used obtaining corresponding esters with acceptable yields and good degree of purity. All the synthesized compounds were tested for their cytotoxic activities in mouse NIH3T3 and human astrocyte cell lines. The esters demonstrated good tolerability and no in vitro cytotoxic effect in both cell cultures. After these promising preliminary results, the esters will be suitable for in vivo studies in order to ascertain their pharmacokinetic characteristics and their biological effects.

Observation of peak neoclassical toroidal viscous force in the DIII-D tokamak.

Observation of a theoretically predicted peak in the neoclassical toroidal viscosity (NTV) force as a function of toroidal plasma rotation rate Ω is reported. The NTV was generated by applying n=3 magnetic fields from internal coils to low Ω plasmas produced with nearly balanced neutral beam injection. Locally, the peak corresponds to a toroidal rotation rate Ω(0) where the radial electric field E(r) is near zero as determined by radial ion force balance.

Evidence for the importance of trapped particle resonances for resistive wall mode stability in high beta tokamak plasmas.

Active measurements of the plasma stability in tokamak plasmas reveal the importance of kinetic resonances for resistive wall mode stability. The rotation dependence of the magnetic plasma response to externally applied quasistatic n=1 magnetic fields clearly shows the signatures of an interaction between the resistive wall mode and the precession and bounce motions of trapped thermal ions, as predicted by a perturbative model of plasma stability including kinetic effects. The identification of the stabilization mechanism is an essential step towards quantitative predictions for the prospects of "passive" resistive wall mode stabilization, i.e., without the use of an "active" feedback system, in fusion-alpha heated plasmas.

Integration of full divertor detachment with improved core confinement for tokamak fusion plasmas.

Divertor detachment offers a promising solution to the challenge of plasma-wall interactions for steady-state operation of fusion reactors. Here, we demonstrate the excellent compatibility of actively controlled full divertor detachment with a high-performance (ßN ~ 3, H98 ~ 1.5) core plasma, using high-ßp (poloidal beta, ßp > 2) scenario characterized by a sustained core internal transport barrier (ITB) and a modest edge transport barrier (ETB) in DIII-D tokamak. The high-ßp high-confinement scenario facilitates divertor detachment which, in turn, promotes the development of an even stronger ITB at large radius with a weaker ETB. This self-organized synergy between ITB and ETB, leads to a net gain in energy confinement, in contrast to the net confinement loss caused by divertor detachment in standard H-modes. These results show the potential of integrating excellent core plasma performance with an efficient divertor solution, an essential step towards steady-state operation of reactor-grade plasmas.

Waste management and competitiveness of firms in Europe: A stochastic frontier approach.

The present paper aims to investigate the relationship between achieved recycling rates and the competitiveness of firms working in circular economy sectors. The econometric analysis is based on the Stochastic Frontier Analysis (a parametric model) and is carried out in reference to seventeen European countries over the years 2010-2016. It reveals intriguing results about the positive effect that achieved recycling rates of packaging, electronic and bio-waste can exert on the competitiveness of firms, although differences emerge across the countries considered. Furthermore, through the inefficiency function, a positive effect of R&D spending on competitiveness of European firms is disclosed.

Laparoscopic hyperthermic intraperitoneal peroperative chemotherapy (HIPEC) in the management of refractory malignant ascites: A multi-institutional retrospective analysis in 52 patients.

Malignant ascites is a debilitating condition affecting cancer patients in their terminal stage of disease. Recently, laparoscopic hyperthermic intraperitoneal peroperative chemotherapy (HIPEC) was introduced as a new approach. From September 2001 to August 2008, 52 patients were treated with this new modality. No treatment-related mortality was observed. Median survival was 98 days. One patient developed a clinical recurrence. Laparoscopic HIPEC is a safe and effective method for palliating malignant ascites.

The effects of lipopolysaccharide-induced reactive oxygen species were blunted by calcium oxalate in renal tubular epithelial cells.

BACKGROUND/AIM: Previously we demonstrated that calcium oxalate (CaOx) in LLC-PK1 cells and oxalate in MDCK cells induce tubular damage and greater glycosaminoglycan synthesis. We test the hypothesis that reactive oxygen species (ROS) and prostaglandins mediate these effects. METHODS: LLC-PK1 and MDCK cells were exposed to graded concentrations of CaOx, oxalate or both. Glycosaminoglycan synthesis was analyzed through metabolic labeling and gel electrophoresis. Cell permeability and lipid peroxidation were assessed by lactate dehydrogenase release and malondialdehyde levels. Hydrogen peroxide and superoxide anion were analyzed using 2',7'-dichlorofluorescein and luminol. Cyclooxygenase-2 expression and prostaglandin E2 production were assessed by RT-PCR and ELISA, respectively. RESULTS: In LLC-PK1 cells exposed to CaOx, we observed increased cell permeability, no induction of ROS or lipid peroxidation, inability to produce lipopolysaccharide-induced ROS and increases in prostaglandin E2. Indomethacin used alone increased glycosaminoglycan synthesis but did not potentiate CaOx-induced effects. In MDCK cells exposed to oxalate we observed increased cell permeability, ROS production only at higher concentrations and inability to produce lipopolysaccharide-induced ROS. Indomethacin alone had no effect but increased oxalate-induced glycosaminoglycan synthesis. CONCLUSIONS: Prostaglandins modulate endogenous production of glycosaminoglycans in LLC-PK1 cells, as well as regulate oxalate-induced glycosaminoglycan synthesis in MDCK cells. Rather than increasing, CaOx and oxalate blunted lipopolysaccharide-induced ROS production. We could speculate that patients with recurrent nephrolithiasis may lose antimicrobial protection induced by ROS during infections.

The registry of brain deaths in quality control program: evaluation of potentiality of each hospital in Abruzzo and Molise regions.

Quality control procedures in donation and transplantation of organ and tissue, which were started in 2001, are aspects of the activity of Regional Centre for Transplantation. Over the years there has been a significant increase in the number of diagnosed brain deaths that is close to the figure reported in the international literature of 50/60 per million inhabitants (p.m.i). Misidentification of brain death is still the most important cause of loss of organs for transplantation; in fact in Italy, there are some regions that overcome this value, but there are other regions in which the number of brain death identified is still low. Abruzzo and Molise in 2003 achieved the highest registered brain deaths (61 p.m.i.); in 2004, 51; in 2005, 43; and the projection for 2006 is about around 50. For this study we collected data from five hospitals with a neurosurgical unit, which were representative of procurement activity in two regions, because they had identified the most brain deaths, 53/65 in 2005. The data were compared among hospitals and with the Spanish country data (1999-2003), which was avant-garde for the processing of organ donation and transplantation in Europe. Some useful indices to define the theoretical capacity of donation for each hospital (ability to identify brain death, the cause of donor loss) were evaluated for determining the efficacy of the procedure in organ procurement.

Laparoscopic intraperitoneal hyperthermic chemotherapy for palliation of debilitating malignant ascites.

AIM: To report the use of laparoscopic Intraperitoneal Hyperthermic Chemotherapy (LIPHC) in the treatment of malignant ascites. METHODS: From September 2001 to December 2003, 14 patients between the age of 56 and 78years were treated. Ascites was from gastric cancer (5 cases), colorectal cancer (3 cases), ovarian cancer (3 cases), breast cancer (2 cases) and peritoneal mesothelioma (1 case). The LIPHC was carried out at 42 degrees C for 90 min with 1.5% dextrose solution as a carrier. Chemotherapy was cisplatin and doxorubicin or mitomycin depending on the type of primary tumor. The drains were left in situ after surgery and removed when perfuse drainage ceased. RESULTS: Ascites was controlled in all the treated cases. A CT scan performed in follow-up showed a small, clinically undetectable, fluid accumulation in the pelvis of one patient. CONCLUSIONS: This method resulted in benefit for those peritoneal carcinomatosis patients with debilitating malignant ascites who were excluded from cytoreductive surgery. Proficiency in laparoscopic staging procedures and experience in the management of carcinomatosis and intraperitoneal hyperthermic chemotherapy (IPHC) are required for the success of the procedure.

An approach to the stereo-controlled synthesis of polycyclic derivatives of l-4-thiazolidinecarboxylic acid active against HIV-1 integrase.

Herein, we describe a new strategy for the preparation of thiazolothiazepine-based inhibitors of human immunodeficiency virus type-1 integrase (IN). The present method allows facile preparation of the title compounds in a single enantiomeric form starting from l-4-thiazolidinecarboxylic acid. This method could be easily extended to the synthesis of several analogs derived from optically active cyclic aminoacids. We also present a putative model showing the interaction between l- and d-isomers of compound 1 in the IN active site. A sensibly lower IC(50) value was found for (-)-1 over racemic-1 in an anti-IN assay.

120 peritoneal carcinomatoses from colorectal cancer treated with peritonectomy and intra-abdominal chemohyperthermia: a S.I.T.I.L.O. multicentric study.

A multicentric study has been carried out on 120 patients affected by peritoneal carcinomatosis from colorectal cancer. Patients have been treated by cytoreductive surgery and intra-operative hyperthermic chemoperfusion (HIPEC) with cisplatin (CDDP) and mitomycin-c (MMC). A small group of patients were treated with oxaliplatin (LOHP) following the Elias et al. scheme [intravenous 5-fluorouracil (400 mg/m2) and leucovorin (20 mg/m2) followed by intraperitoneal perfusion with LOHP (460 mg/m2) in 2 l/m2, during 30 min at 43 degrees C]. CC-0 cytoreduction was achieved in 85.2% of the patients. Major morbidity and mortality was 22.5% and 3.3%, respectively. No G4 toxicity was registered. The three-year survival was 25.8%. The difference in survival evaluating complete cytoreduction (CC-0) vs. incomplete (CC1-2; residual tumor nodules greater than 2.5 mm) was statistically significant (p < 0.0001). Evaluating only the patients that could be cytoreduced to CC-0, the 3-year survival was raised to 33.5%. In our experience the peritoneal cancer index (PCI) has been demonstrated to be a weak prognostic factor reaching a statistical significance only after the exclusion of patients with resected hepatic metastases. The patients treated with oxaliplatin were alive and free-of-disease after a 16-month median follow-up.

Effect of interleukin-1-beta on metastasis formation in different tumor systems.

Experiments were done to determine the effect of interleukin-1-beta (IL-1 beta) on metastasis formation in different tumor systems. Intravenous administration of 1 microgram of human recombinant IL-1 beta given 1 hour before tumor cell injection augmented lung colony formation (experimental metastases) by the human A375 melanoma variants, the human HT-29M colon carcinoma, the SN12-K1 renal carcinoma in nude mice, the murine B16 melanoma variants, and the murine UV-2237M fibrosarcoma in syngeneic recipients. The same treatment did not induce lung colony formation by a human rectal carcinoma (HCC-P2988) or by a murine reticulum cell sarcoma (M5076), both of which are not metastatic to the lung. Spontaneous metastases were studied in C57BL/6 mice bearing the B16-BL6 melanoma (metastatic to the lung) in their footpad and the M5076 reticulum cell sarcoma (metastatic to the liver) subcutaneously. Daily intraperitoneal treatment with 1 microgram of IL-1 beta increased lung and liver metastases. These findings indicate that treatment of mice with IL-1 beta can increase the number of artificial or spontaneous metastases and that this effect is not limited to a single tumor type or to a specific organ.