Oxaliplatin use in pressurized intraperitoneal aerosol chemotherapy (PIPAC) is safe and effective: A multicenter study.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new drug delivery method used in patients with peritoneal cancer (PC) of primary or secondary origin. Intraperitoneal use of oxaliplatin raises concerns about toxicity, especially abdominal pain. The objective of this study was to assess the tolerance of PIPAC with oxaliplatin (PIPAC-Ox) in a large cohort of patients and to identify the risk factors for high grade toxicity, discontinuation of treatment and impaired survival. This retrospective cohort study included all consecutive patients treated with PIPAC-Ox (92 mg/m <sup>2</sup> ) in five centers specialized in the treatment of PC. The procedure was repeated every 6 weeks. Outcomes of interest were Common Terminology Criteria for Adverse Events (CTCAE), symptoms and survival (Kaplan-Meier). Univariate risk factors were included in a multinominal regression model to control for bias. Overall, 251 PIPAC-Ox treatments were performed in 101 patients (45 female) having unresectable PC of various origins: 66 colorectal, 15 gastric, 5 ovarian, 3 mesothelioma, 2 pseudomyxoma, 10 other malignancies (biliary, pancreatic, endocrine) respectively. The median PCI was 19 (IQR: 10-28). Postoperative abdominal pain was present in 23 patients. Out of the 9 patients with grade 3 abdominal pain, only 3 needed a change of PIPAC drug. CTCAE 4.0 toxicity grade 4 or higher was encountered in 16(15.9%) patients. The patients had a mean of 2.5 procedures/patient (SD = 1.5). 50 subjects presented with symptom improvement. Oxaliplatin-based PIPAC appears to be a safe treatment that offers good symptom control and promising survival for patients with advanced peritoneal disease

Experimental study of super-rotation in a magnetostrophic spherical Couette flow

We report measurements of electric potentials at the surface of a spherical container of liquid sodium in which a magnetized inner core is differentially rotating. The azimuthal angular velocities inferred from these potentials reveal a strong super-rotation of the liquid sodium in the equatorial region, for small differential rotation. Super-rotation was observed in numerical simulations by Dormy et al. [1]. We find that the latitudinal variation of the electric potentials in our experiments differs markedly from the predictions of a similar numerical model, suggesting that some of the assumptions used in the model - steadiness, equatorial symmetry, and linear treatment for the evolution of both the magnetic and velocity fields - are violated in the experiments. In addition, radial velocity measurements, using ultrasonic Doppler velocimetry, provide evidence of oscillatory motion near the outer sphere at low latitude: it is viewed as the signature of an instability of the super-rotating region

Zonal shear and super-rotation in a magnetized spherical Couette flow experiment

We present measurements performed in a spherical shell filled with liquid sodium, where a 74 mm-radius inner sphere is rotated while a 210 mm-radius outer sphere is at rest. The inner sphere holds a dipolar magnetic field and acts as a magnetic propeller when rotated. In this experimental set-up called DTS, direct measurements of the velocity are performed by ultrasonic Doppler velocimetry. Differences in electric potential and the induced magnetic field are also measured to characterize the magnetohydrodynamic flow. Rotation frequencies of the inner sphere are varied between -30 Hz and +30 Hz, the magnetic Reynolds number based on measured sodium velocities and on the shell radius reaching to about 33. We have investigated the mean axisymmetric part of the flow, which consists of differential rotation. Strong super-rotation of the fluid with respect to the rotating inner sphere is directly measured. It is found that the organization of the mean flow does not change much throughout the entire range of parameters covered by our experiment. The direct measurements of zonal velocity give a nice illustration of Ferraro's law of isorotation in the vicinity of the inner sphere where magnetic forces dominate inertial ones. The transition from a Ferraro regime in the interior to a geostrophic regime, where inertial forces predominate, in the outer regions has been well documented. It takes place where the local Elsasser number is about 1. A quantitative agreement with non-linear numerical simulations is obtained when keeping the same Elsasser number. The experiments also reveal a region that violates Ferraro's law just above the inner sphere.Comment: Phys Rev E, in pres

Insights into metazoan evolution from <i>Alvinella pompejana</i> cDNAs

BackgroundAlvinella pompejana is a representative of Annelids, a key phylum for evo-devo studies that is still poorly studied at the sequence level. A. pompejana inhabits deep-sea hydrothermal vents and is currently known as one of the most thermotolerant Eukaryotes in marine environments, withstanding the largest known chemical and thermal ranges (from 5 to 105°C). This tube-dwelling worm forms dense colonies on the surface of hydrothermal chimneys and can withstand long periods of hypo/anoxia and long phases of exposure to hydrogen sulphides. A. pompejana specifically inhabits chimney walls of hydrothermal vents on the East Pacific Rise. To survive, Alvinella has developed numerous adaptations at the physiological and molecular levels, such as an increase in the thermostability of proteins and protein complexes. It represents an outstanding model organism for studying adaptation to harsh physicochemical conditions and for isolating stable macromolecules resistant to high temperatures.ResultsWe have constructed four full length enriched cDNA libraries to investigate the biology and evolution of this intriguing animal. Analysis of more than 75,000 high quality reads led to the identification of 15,858 transcripts and 9,221 putative protein sequences. Our annotation reveals a good coverage of most animal pathways and networks with a prevalence of transcripts involved in oxidative stress resistance, detoxification, anti-bacterial defence, and heat shock protection. Alvinella proteins seem to show a slow evolutionary rate and a higher similarity with proteins from Vertebrates compared to proteins from Arthropods or Nematodes. Their composition shows enrichment in positively charged amino acids that might contribute to their thermostability. The gene content of Alvinella reveals that an important pool of genes previously considered to be specific to Deuterostomes were in fact already present in the last common ancestor of the Bilaterian animals, but have been secondarily lost in model invertebrates. This pool is enriched in glycoproteins that play a key role in intercellular communication, hormonal regulation and immunity.ConclusionsOur study starts to unravel the gene content and sequence evolution of a deep-sea annelid, revealing key features in eukaryote adaptation to extreme environmental conditions and highlighting the proximity of Annelids and Vertebrates

Rapidly rotating spherical Couette flow in a dipolar magnetic field : an experimental study of the mean axisymmetric flow

In order to explore the magnetostrophic regime expected for planetary cores, experiments have been conducted in a rotating sphere filled with liquid sodium, with an imposed dipolar magnetic field (the DTS setup). The field is produced by a permanent magnet enclosed in an inner sphere, which can rotate at a separate rate, producing a spherical Couette flow. The flow properties are investigated by measuring electric potentials on the outer sphere, the induced magnetic field in the laboratory frame, and velocity profiles inside the liquid sodium using ultrasonic Doppler velocimetry. The present article focuses on the time-averaged axisymmetric part of the flow. The Doppler profiles show that the angular velocity of the fluid is relatively uniform in most of the fluid shell, but rises near the inner sphere, revealing the presence of a magnetic wind, and gently drops towards the outer sphere. The transition from a magnetostrophic flow near the inner sphere to a geostrophic flow near the outer sphere is controlled by the local Elsasser number. For Rossby numbers up to order 1, the observed velocity profiles all show a similar shape. Numerical simulations in the linear regime are computed, and synthetic velocity profiles are compared with the measured ones. In the geostrophic region, a torque-balance model provides very good predictions. We find that the induced magnetic field varies in a consistent fashion, and displays a peculiar peak in the counter-rotating regime. This happens when the fluid rotation rate is almost equal and opposite to the outer sphere rotation rate. The fluid is then almost at rest in the laboratory frame, and the Proudman-Taylor constraint vanishes, enabling a strong meridional flow. We suggest that dynamo action might be favored in such a situation

Incidence and Risk Factors Related to Symptomatic Venous Thromboembolic Events After Esophagectomy for Cancer.

Major oncologic surgery is associated with a high incidence of venous thromboembolic events (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE). However, the incidence and risk factors for symptomatic VTE during curative treatment for patients with esophageal cancer are poorly documented. Data were collected from 30 European centers from 2000 to 2010. The incidence of in-hospital VTE was assessed in 2,944 patients with esophageal cancer having surgery with curative intent, and 50 clinically relevant parameters were assessed as potential risk factors for VTE. Patients received low molecular weight heparin prophylaxis during hospital stay and for 4 weeks after surgery. Eighty-four patients (2.9%) developed a symptomatic VTE; all of them had a DVT and 44 were also diagnosed with a PE. In the VTE group there were 19 postoperative deaths recorded, 5 of which (26.3%) were directly caused by PE at postoperative days 7, 10, 21, 45, and 48 despite VTE prophylaxis. In-hospital postoperative mortality was significantly higher in VTE patients (23% versus 7%, p &lt; 0.001) and mean hospital stay was also longer in this group (33 ± 24 versus 25 ± 21 days, p &lt; 0.001). Multivariable analysis showed that high American Society of Anesthesiologists (ASA) class (p = 0.008), pneumopathy (p = 0.002), or an acute respiratory distress syndrome (ARDS) (p = 0.015) were significantly associated with VTE. Patients with ASA class III or IV and those who present a postoperative pneumopathy or ARDS seem to be at higher risk for VTE. Thus, current VTE screening and thromboprophylaxis for these patients might be inadequate and needs further investigation

Anti-Thy-1 antibody-induced neurite outgrowth in cultured dorsal root ganglionic neurons is mediated by the c-Src-MEK signaling pathway.

Our previous study has shown that anti-Thy-1 antibody promotes neurite outgrowth of cultured dorsal root ganglion( DRG) neurons in a protein kinase A (PKA)-dependent manner. The present study provided another intracellular signaling pathway for the neurotrophic effect of anti-Thy-1 antibody. In DMSO-treated control cells, Thy-1 was enriched in microdomain -like structures on cell membranes by immunofluorescence observation. Treatment of DRG neurons with anti-Thy-1 antibody not only stimulated neurite outgrowth, but also increased the branching complexity of the neurites in both small and large neurons. We have previously shown that anti-Thy-1 antibody causes a time- dependent activation of mitogen- activated protein kinase ( MEK) and of cyclic AMP response-element binding protein ( CREB). Here, anti-Thy-1 antibody elicited a transient activation of c-Src kinase, and the activation of c-Src kinase appeared occurring upstream of the activation of MEK and CREB, since pretreatment with the Src kinase inhibitor, PP2, effectively abolished the anti-Thy-1 antibody-induced neurite outgrowth and the phosphorylation of MEK and CREB . CREB phosphorylation might result in upregulation of certain neurite outgrowth-related proteins. We therefore conclude that anti-Thy-1 antibody activates the c-Src kinase-MEK-CREB cascade and overcomes the inhibitory effect of Thy-1 on neurite outgrowth in DRG neurons