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Sheared flows are known to reduce turbulent transport by decreasing the correlation length and/or intensity of turbulent structures. The transport barrier that takes place at the edge during improved regimes such as H mode, corresponds to the establishment of a large shear of the radial electric field. In this context, the radial shape of the radial electric field or more exactly of the perpendicular E × B velocity appears as a key element in accessing improved confinement regimes. In this paper, we present the radial profile of the perpendicular velocity measured using Doppler back-scattering system at the edge of the plasma, dominated by the E × B velocity, during the first campaigns of the WEST tokamak. It is found that the radial velocity profile is clearly more sheared in lower single null configuration (with the B × ∇B magnetic drift pointing toward the active X-point) than in upper single null configuration for ohmic and low current plasmas (B = 3.7 T and q 95 = 4.7), consistently with the expectation comparing respectively ‘favourable’ versus ‘unfavourable’ configuration. Interestingly, this tendency is sensitive to the plasma current and to the amount of additional heating power leading to plasma conditions in which the E × B velocity exhibits a deeper well in USN configuration. For example, while the velocity profile exhibits a clear and deep well just inside the separatrix concomitant with the formation of a density pedestal during L–H transitions observed in LSN configuration, deeper E r wells are observed in USN configuration during similar transitions with less pronounced density pedestal.

The prognosis of patients with advanced soft-tissue sarcomas (STS) remains dismal, and systemic therapeutic options are limited. Early phase trials are becoming increasingly safe and effective. This study aimed to identify the prognostic factors for progression-free survival (PFS).This retrospective analysis included all STS patients participating in early phase trials at Gustave Roussy and Léon Bérard between 1 January 2012 and 31 December 2020.Overall, 199 patients accounted for 214 inclusions in advanced STS. The most frequent histotypes were well-differentiated/dedifferentiated liposarcomas (n = 55), leiomyosarcomas (n = 53), synovial sarcomas (n = 22), undifferentiated pleomorphic sarcomas (n = 15), angiosarcomas (n = 12), and myxoid liposarcomas (n = 10). The median PFS was 2.8 months (95% confidence interval 2.7-4.1 months). The median PFS in the first, second, and later lines was 8.3, 5.4, and 2.6 months, respectively (P = 0.00015). The median PFS was 2.8 months in case of molecular screening, 4.1 months in case of histology-driven screening, and 1.6 months (P = 0.00014) in the absence of either screening modalities. In univariate analysis, histotype (P = 0.026), complex genomics (P = 0.008), number of prior lines (P0.001), prior anthracyclines (P0.001), number of metastatic sites (P = 0.003), liver metastasis (P0.001), lung metastasis (P0.001), absence of molecular or histology-driven screening (P0.001), first-in-human trials (P0.001), dose-escalation cohorts (P = 0.011), and Royal Marsden Hospital (RMH) score1 (P0.001) were significantly associated with shorter PFS. In multivariate analysis, independent prognostic factors for shorter PFS were myxoid liposarcoma (P = 0.031), ≥2 prior lines of treatment (P = 0.033), liver metastasis (P = 0.007), and RMH score2 (P = 0.006). Factors associated with improved PFS were leiomyosarcomas (P = 0.010), molecular screening (P = 0.025), and histology-driven screening (P = 0.010). The median overall survival rates were 36.3, 12.6, and 9.2 months in the first, second, and later lines, respectively (P = 0.0067). The grade 3-4 toxicity rate was 36%.Early phase trials provide an active therapeutic option for STS, even in first-line settings. Molecular screening and histology-driven trials further improve the clinical benefit.

Background Desmoplastic Small Round Cell Tumor (DSRCT) is a rare disease affecting predominantly children and young adults and for which the benefit of hyperthermic intraperitoneal chemotherapy (HIPEC) after complete cytoreductive surgery (CCRS) remains unknown. Methods To identify patients with DSRCT without extraperitoneal metastases (EPM) who underwent CCRS between 1991 and 2015, a retrospective nation-wide survey was conducted by crossing the prospective and retrospective databases of the French Network for Rare Peritoneal Malignancies, French Reference Network in Sarcoma Pathology, French Sarcoma Clinical Network and French Pediatric Cancer Society. Results Among the 107 patients with DSRCT, 48 had no EPM and underwent CCRS. The median peritoneal cancer index (PCI) was 9 (range: 2–27). Among these 48 patients, 38 (79%) had pre- and/or postoperative chemotherapy and 23 (48%) postoperative whole abdominopelvic radiotherapy (WAP-RT). Intraperitoneal chemotherapy was administered to 11 patients (23%): two received early postoperative intraperitoneal chemotherapy (EPIC) and nine HIPEC. After a median follow-up of 30 months, the median overall survival (OS) of the entire cohort was 42 months. The 2-y and 5-y OS were 72% and 19%. The 2-y and 5-y disease-free survival (DFS) were 30% and 12%. WAP-RT was the only variable associated with longer peritoneal recurrence-free survival and DFS after CCRS. The influence of HIPEC/EPIC on OS and DFS was not statistically conclusive. Conclusion The benefit of HIPEC is still unknown and should be evaluated in a prospective trial. The value of postoperative WAP-RT seems to be confirmed.

Soft-tissue sarcoma of the limbs or the trunk wall determine a heterogeneous group of tumours that tends to receive a more individualized approach. The surgeon in charge with soft-tissue sarcoma has to be familiar with these tumours in order to deliver an adequate treatment. Most important is the initial diagnostic procedure, comprising imaging with MRI, a core needle biopsy, and in France, referral to a centre of expertise within the clinical network NETSARC. Prior to surgery, a multidisciplinary conference determines its moment and the extent of surgical resection within the frame of a multidisciplinary approach, and also plans reconstructive surgery, when needed. A standardized operative report summarizes items necessary to describe the resection quality (i.e. tumour seen, tumour infiltrated?). In multidisciplinary staff meetings, they are compared to margins measured by the pathologist on the operative specimen. Hence, resection quality is determined collegially and defined by resection type R (R0, R1, R2) as a qualitative result. The quality of resection directly determines the 5-year risk of local recurrence, estimated between 10 and 20% in specialized centres, with the objective to attain 10%. Early rehabilitation favours better functional outcome. The surgeon's experience with soft-tissue sarcoma, as part of a multidisciplinary treatment, is key in achieving the best adequacy between oncological resection and favourable functional outcome. In France, a specific university course for soft-tissue sarcoma will be set-up.

This paper describes both an experimental study and a numerical investigation of the transverse mechanical behaviour of unidirectional polypropylene/glass fibre composites. A deterministic numerical simulation of the mechanical damage that accounts for the organization within real composites is proposed. This numerical method is based on classical finite element analysis, with tailored phase arrangement that unequivocally accounts for the real samples. This technique permitted some light to be shed on the origin of the transverse brittleness of these composites. It is shown that the number of damaged zones as a function of the applied strain follows a Weibull distribution. The influence of the volume fraction of filler was also estimated, both through experimental and numerical ways. It can be concluded that the reduction of the average distance between fibres increases the local stress enhancement and favours the degradation mechanisms of composites, especially at the glass fibres/polymer interface. The paper also proposes a novel analytical relationship linking the number of damaged zones to the macroscopic transverse mechanical behaviour of commingled composites.

Backscattering of a microwave beam close to the cut-off allows for measurement of density fluctuations at a specified wave-number, selected by the scattering geometry , where ki is the beam wave-number at the reflection layer. On the Doppler reflectometry system installed on Tore Supra, both the scattering wave-number k⊥ and the scattering localization (r/a) can be changed during the shot owing to the steppable probing frequency and the motorized antenna. Operating in O mode, the spatial and wave-number ranges depend essentially on density profile, typically probing 0.5 < r/a < 0.95 and 2 < k < 15 cm−1. Wave number spectra are similar to those obtained with conventional scattering systems. The perpendicular fluctuation velocity in the laboratory frame is obtained from the Doppler shift of the frequency spectrum Δω = k⊥v⊥. It is dominated by the plasma Er × B velocity. In the core, the latter is mainly due to the projection of the toroidal velocity, as this is shown by comparison with measurements by charge exchange recombination spectroscopy. In the set of analysed Tore Supra ohmic and ICRH plasmas, the observed rotation is consistent with a poloidal velocity in the electron diamagnetic direction and/or a toroidal velocity in the counter current direction. The detailed structure of the velocity profile, at the edge and in different plasma regimes, allows us then to get information on the radial electric field distribution. The dynamics of the fluctuation velocity can be studied from the time frequency analysis of the signal, for investigating intermittent behaviour and transient regimes.

A new generation of broadband reflectometers based on solid state components has been installed on Tore-Supra. With reflectometers covering the range 50 to 155 GHz, the whole plasma can be scanned. Two X-mode reflectometers (V and W band) are dedicated to electron density profile measurements. Diagnostics are operated routinely with an automatic algorithm to reconstruct the density profile from shot to shot. A fast acquisition mode is available to study short time plasma evolution. For turbulence and transport studies, a third reflectometer operating between 105 and 155 GHz measures density fluctuations in the plasma centre. Sensitive to large scales, it can retrieve density perturbation due to MHD modes or broadband turbulence. Lastly, a Doppler reflectometer, based on back scattering, is being installed for measuring the poloidal rotation and fluctuations amplitude at higher wave numbers.

High uncertainties affect black carbon (BC) emissions and, despite its important impact on air pollution and climate, very few BC emissions evaluations are found in the literature. This paper presents a novel approach, based on airborne measurements across the Paris plume, developed in order to evaluate BC and NOx emissions at the scale of a whole agglomeration. The methodology consists in integrating, for each transect, across the plume observed and simulated concentrations above background. This allows minimizing several error sources in the model (e.g. representativeness, chemistry, plume lateral dispersion). The procedure is applied with the CHIMERE chemistry-transport model to three inventories – the EMEP inventory, and the so-called TNO and TNO-MP inventories – over the month of July 2009. Various systematic uncertainty sources both in the model (e.g. boundary layer height, vertical mixing, deposition) and in observations (e.g. BC nature) are discussed and quantified, notably though sensitivity tests. A statistically significant (but moderate) overestimation is obtained on the TNO BC emissions and on EMEP and TNO-MP NOx emissions, as well as on the BC/NOx emission ratio in TNO-MP. The benefit of the airborne approach is discussed through a comparison with the BC/NOx ratio at a ground site in Paris, which additionally suggests potential error compensations in the BC emissions spatial distribution over the agglomeration.

The only two procedures for surgical treatment of ultra-low rectal cancer without a permanent abdominal stoma are the intersphincteric resection (ISR) and the abdominoperineal resection (APR) plus a perineal pseudocontinent colostomy (PCC). This study compared functional results and quality of life following these two techniques.Between January 1995 and December 2011, 36 patients had undergone an ISR (n = 14) or a PPC (n = 22) for very low rectal cancer. The Cleveland Clinica Florida (Wexner) fecal incontinence questionnaire and the EORTC Quality of Life questionnaire QLQ-C30 and CR38 had been administered.There were no differences in gender, age, the interval between surgery and questionnaire responses, preoperative TNM staging, perioperative treatment, the laparoscopic approach and circumferential margin involvement rate between the groups. The ISR and PPC led to no difference in quality of life (Qol) and continence with a median Wexner score of respectively 11 and 10 (P = 0.403) and a fecal incontinence rate of 58.2% and 41% (P = 0.221). The incontinent patients had experienced worse social functioning and tended to have worse overall health. The patients who had undergone ISR had more defecation problems and evacuation difficulties.Qol and continence are similar between ISR and PPC.

Introduction The poor prognosis of signet ring cell (SRC) eso-gastric adenocarcinoma (EGA) might be explained by its great affinity for the peritoneum. The aim of this study was to identify predictors of peritoneal carcinomatosis recurrence (PCR) after curative surgery and hence identify high risk patients. Methods A retrospective national survey was conducted over 19 French surgical centers between 1997 and 2010. Patients with non-metastatic disease who benefited from curative surgery without postoperative death were included. Event-free patients who did not reach the time point of 24 months were excluded. Results In a cohort of 3010 patients, 1050 were SRC EGA and 424 patients met the selection criteria. The tumor location was mainly gastric (68.9%) and a total gastrectomy was performed in 218 patients (51.4%). Chemoradiotherapy or chemotherapy alone was given preoperatively to 71 (16.7%) and postoperatively to 150 (35.4%) patients. After a median follow-up of 54 months, recurrence was diagnosed in 214 patients (50.5%) within a mean delay of 17 ± 10.7 months. PCR was diagnosed in 81 patients (19.1%). In multivariable analysis, four factors were identified as predictors of PCR: linitis plastica ( p p = 0.022; OR = 1.58), lymph node involvement ( p = 0.005; OR = 1.7) and tumors of gastric origin ( p = 0.026; OR = 2.36), with PCR rates of 55%, 26%, 23% and 22%, respectively. Conclusion Identification of strong predictors for PCR among this large series of SRC EGA patients helps to identify subgroups of patients that may benefit from specific therapeutic strategies such as prophylactic hyperthermic intraperitoneal chemotherapy.

International audience; This paper presents an overview of recent advances in modeling and measurements of turbulence in Tore Supra plasmas. Spatio‐temporal properties of turbulence are discussed in relation with transport models. An explanation is proposed for the k−3 decay of wave number spectra, which are observed by using both coherent laser scattering and Doppler reflectometry. Also the interplay between turbulence and flows has been investigated. It is shown that toroidal rotation results from a competition between neoclassical and turbulence flow generation. Finally a new method has been proposed to determine the transport coefficients of impurities. These coefficients are usually well above the neoclassical prediction.

Colorectal cancer is the most frequent digestive cancer. Prognosis is greatly depending on the TNM stage at the time of diagnosis. Fifty percent of all patients shall develop, synchronously or metachronously, liver metastases. Different means such as chemotherapy, targeted therapies, radiofrequency ablation, portal vein embolization and two-stage hepatectomy may be used to make these metastases eventually resectable and to increase overall survival. This is a short review of these different methods used to increase resectability but also on the integration of these parameters in a larger approach of colorectal liver metastasis surgery especially insisting on multidisciplinary discussion.

We report the case of a 65-year-old man admitted for an upper-GI hemorrhage. A CT scan performed with vascular reconstructions demonstrated a pseudoaneurysm of the left gastric artery. Proximal vascular control of the celiac axis was obtained by balloon occlusion with a Fogarty balloon inserted retrograde via the femoral artery: the pseudoaneurysm was then successfully controlled with direct suture.

6000 new cases of colorectal cancer are diagnosed each year in Belgium. 50% of these patients shall develop liver metastasis. Resection remains the only chance of long term survival and must be considered as an endpoint from the beginning of the treatment. It is the result of a multidisciplinary discussion and a global approach of the disease. It is rarely directly feasible, but there are many techniques which may make it achievable in the end. Today, resection criteria are exclusively technical and neither bad prognosis factors, nor the presence of extra-hepatic metastases should exclude liver resection. This resection must be assessed by a confirmed hepatobiliary surgeon and must be proposed to all patients whatever their age as long as their general state of health is good.

The contribution of endothelin-1 (ET-1) to vascular hyper-reactivity associated with chronic ethanol intake, a major risk factor in several cardiovascular diseases, remains to be investigated.The biphasic haemodynamic responses to ET-1 (0.01-0.1 nmol kg(-1), i.v.) or to the selective ETB agonist, IRL1620 (0.001-1.0 nmol kg(-1), i.v.), with or without ETA or ETB antagonists (BQ123 (c(DTrp-Dasp-Pro-Dval-Leu)) at 1 and 2.5 mg kg(-1) and BQ788 (N-cis-2,6-dimethyl-piperidinocarbonyl-L-gamma-methylleucyl1-D-1methoxycarbonyltryptophanyl-D-norleucine) at 0.25 mg kg(-1), respectively) were tested in anaesthetized rats, after 2 weeks' chronic ethanol treatment. Hepatic parameters and ET receptor protein levels were also determined.The initial hypotensive responses to ET-1 or IRL1620 were unaffected by chronic ethanol intake, whereas the subsequent pressor effects induced by ET-1, but not by IRL1620, were potentiated. BQ123 at 2.5 but not 1 mg kg(-1) reduced the pressor responses to ET-1 in ethanol-treated rats. Conversely, BQ788 (0.25 mg kg(-1)) potentiated ET-1-induced increases in mean arterial blood pressure in control as well as in ethanol-treated rats. Interestingly, in the latter group, increases in heart rate, induced by ET-1 at a dose of 0.025 mg kg(-1) were enhanced following ETB receptor blockade. Finally, we observed higher levels of ETA receptor in the heart and mesenteric artery and a reduction of ETB receptor protein levels in the aorta and kidney from rats chronically treated with ethanol.Increased vascular reactivity to ET-1 and altered protein levels of ETA and ETB receptors could play a role in the pathogenesis of cardiovascular complications associated with chronic ethanol consumption.

Hemobilia or hematobilia is defined by bleeding inside the bile duct. Although rare and misunderstood, it may evolve a life-threatening condition and its frequency is increasing. Clinical presentation commonly includes upper gastrointestinal bleeding, biliary colic and jaundice. The diagnosis must be suggested in a patient with a history of hepatic surgery, trauma or invasive biliary intervention. Key investigation is selective angiogram which allows us to confirm the diagnosis, locate and in most cases treat the vascular lesion responsible of hemobilia. Surgery should remain limited to extra-hepatic or gallbladder bleeding and in case of a failure of intra-vascular embolization.

Alveolar echinococcosis is a serious parasitic disease, leading to large hepatic lesions. It must be distinguished from cystic echinococcosis, or hydatic cyst, caused by Echinococcus granulosus. Early diagnosis may allow surgical removal of the lesions by segmental hepatectomy, the only curative treatment. Parasitostatic medical treatment with albendazole may promote stabilization of the disease. Until recently, Belgium was considered a country at very low risk for alveolar echinococcosis, as no human case was reported, despite up to 51% of fox infection in southern Belgium autopsy series. Recently four patients presented with alveolar echinococcosis at the University Hospital Center of Liege, leading to the fear of a possible alveolar echinococcosis endemy in southern Belgium. Two of these patients underwent curative hepatectomy, but the other two had already pulmonary metastases at diagnosis and received palliative albendazole therapy. This article presents these cases, and reviews the clinical features of this parasitic disease.

Until now, Belgium has been considered as a low-risk country for alveolar echinococcosis. However it was recently demonstrated by necropsy series that, in some parts of southern Belgium (Wallonia), up to 51% of the red foxes (Vulpes vulpes) may be infected by E. multilocaris. The authors, working in a university hospital in southern Belgium, described in 2002 the first autochthonous Belgian case of hepatic alveolar echinococcosis. More importantly, in 2004, they diagnosed three other patients with alveolar echinococcosis. One underwent surgical resection, but two others had bilateral pulmonary involvement at time of definite diagnosis. Palliative albendazole therapy was initiated. These patients had been diagnosed with hepatic mass from unknown origin for several months. The previous experience with the first case allowed the authors to consider and to confirm alveolar echinococcosis diagnosis, made by pathology and/or serological tests and imaging. These four patients with alveolar echinococcosis were living either in the Liege or the Luxembourg province. Considering the high prevalence of E. multilocaris infection of red foxes and the recent increase of the fox population due to rabies vaccination in southern Belgium, and also the presence of E. multilocaris infection of red foxes in northern Belgium, it is likely that not only Wallonia, but also maybe the whole Belgium, may face endemic alveolar echinococcosis in the next years.

The endothelin-converting enzyme (ECE) is the main enzyme responsible for the genesis of the potent pressor peptide endothelin-1 (ET-1). It is suggested that the ECE is pivotal in the genesis of ET-1, considering that the knockout of both genes generates the same lethal developments during the embryonic stage. Several isoforms of the ECE have been disclosed, namely ECE-1, ECE-2, and ECE-3. Within each of the first two groups, several sub-isoforms derived through splicing of single genes have also been identified. In this review, the characteristics of each sub-isoform for ECE-1 and 2 will be discussed. It is important to mention that the ECE is, however, not the sole enzyme involved in the genesis of endothelins. Indeed, other moieties, such as chymase and matrix metalloproteinase II, have been suggested to be involved in the production of ET intermediates, such as ET-1 (1–31) and ET-1 (1–32), respectively. Other enzymes, such as the neutral endopeptidase 24–11, is curiously not only involved in the degradation and inactivation of ET-1, but is also responsible for the final production of the peptide via the hydrolysis of ET-1 (1–31). In this review, we will attempt to summarize, through the above-mentioned characteristics, the current wisdom on the role of these different enzymes in the genesis and termination of effect of the most potent pressor peptide reported to date.Key words: endothelin converting enzyme, endothelin-1, isoforms, human, inhibitors, chymase, ET-1 (1–31).

1. We have developed a model to study the inhibitory properties of endogenous autacoids triggered by systemically-administered vasoactive peptides, on platelet aggregation ex vivo in the mouse. 2. Adenosine diphosphate (ADP) (0.5-10 microM) induces a concentration-dependent aggregation of platelet-rich plasma derived from C57BL/6 mice. Intravenously-administered endothelin-1 (0.01-1 nmolx kg(-1)), the selective ETB agonist, IRL-1620 (0.0 -1 nmol x kg(-1)) or bradykinin ( 1-100 nmol x kg(-1)) significantly reduced in a dose-dependent fashion the ADP-induced platelet aggregation. 3. The non-selective cyclo-oxygenase (COX) inhibitor, indomethacin, a selective COX-2 inhibitor NS-398 or the prostacyclin synthase inhibitor, tranylcypromine (10 mg x kg(-1)), markedly reduced the inhibitory properties of endothelin-1, whereas only a combination of both indomethacin, NS-398 or tranylcypromine and L-NAME (10 mg x kg(-1)) were required to abolish the response to bradykinin. 4. An ETB-selective antagonist (BQ-788) or knockout of the B2 receptor gene (in B2 knockout mice) abolishes the platelet inhibitory properties of endothelin-1 and bradykinin, respectively. 5. Our results suggest that intravenously-administered endothelin-1 and bradykinin, through ETB and B2 receptor activation, respectively, inhibit platelet aggregation ex vivo in the mouse. The inhibitory properties of endothelin-1 require the activation of COX-2 and the subsequent generation of prostacyclin. In addition to the two previously mentioned factors, nitric oxide is required for the anti-aggregatory effects of bradykinin.

The endothelins (ET1, ET2, ET3) are a family of peptides that exert vasoactive and mitogenic effects. ETs bind to at least two subtypes of receptors: the ETA subtype is ET1 selective whereas the ETB subtype binds ET1, ET2 and ET3. By RT-PCR, we detected ETA receptor mRNA and ETB receptor mRNA in leiomyoma and in homologous myometrium distal from the tumor. Despite the presence of four spliced variants of ETA receptors, we identified a single class of ETA-binding sites. The level of ETB receptor mRNA was found to be higher in myometrium versus leiomyomas. Using complementary pharmacologic approach, we demonstrated the predominance of ETA receptors in normal myometrium (75% of total receptors). Both ETA and ETB transcripts coexist in leiomyomas, but we have reported only ETA binding sites. Because of growth properties of ET1, we suggest a role for this peptide in the tumoral development of human uterine smooth muscle.

francaisCette breve correspondance montre qu'un delai de l'ordre de quinze ans a separe le travail fondateur de E. N. Lorenz sur le chaos, paru en 1963, de l'acceptation de ses theses par la communaute scientifique. Ce delai est attribue a une resistance habituelle a adopter de nouvelles facons de penser. EnglishThis short correspondence shows that a time lag of about fifteen years separated Edward N. Lorenz's seminal work on chaos theory, published in 1963, from the acceptance of his ideas by atmospheric scientists. This delay is attributed to an usual resistance to a new way of thinking.

Between 1987 and 1988, a survey to determine the distribution of HTLV-I infection was conducted in a representative population of adults, living in southern Chad, Cameroon, and Equatorial Guinea. Populations studied were selected by the cluster sampling technique. Sera were tested for IgG antibodies to HTLV-I by ELISA. ELISA-positive sera were retested by Western blot. The study comprised 2,301 adults, all apparently healthy. Crude prevalence rates range from 0.5 to 11.8%. We found three clearly different areas of HTLV-I seroprevalence rates. An area of low seropositivity in southern Chad and northern Cameroon (0.5-2.0%), an area of moderate seropositivity in the savannah region of Ngaoundere, Cameroon (4.2%) and in Bata, Equatorial Guinea (6.5%), and lastly an area of high seropositivity (8.6-11.8%) in the equatorial forest area of Equatorial Guinea and southern Cameroon. HTLV-I seroprevalence rates increased with age up to 12.6% after 40 years old in the areas of high seropositivity. There was no difference between male and female age-adjusted prevalence rates in all of the areas studied.