Histopathological growth patterns of primary and secondary malignant liver tumors

HGPs are a prognostic and predictive biomarker in patients with malignant liver tumors. They can be classified into desmoplastic HGP (dHGP), replacement HGP (rHGP) and pushing HGP (pHGP). The objective of this thesis was to describe the histopathological growth patterns (HGPs) of primary and secondary malignant liver tumors and to evaluate their association with prognosis after resection. The manuscript is structured in two parts. Part one serves as a general introduction into liver metastases and HGPs. Part two features multiple studies evaluating HGPs in liver metastases from various origins, primary liver tumors and in lung metastases.This manuscript illustrates that the HGPs can be identified in liver tumors, irrespective of specific tumor type, and that they are specific to the liver. This suggests an important role of the liver microenvironment in the underlying biology of HGPs.<br/

Real Time on Moblin/Linux

International audienceThe automotive manufacturers are more than ever facing many challenges. With the tremendous involvement of electronics in the achievement of end-customers needs, automotive suppliers must accommodate themselves to the constantly changing features of carmakers. Infotainment is one of the most challenging fields, where the carmakers and suppliers realized that the use of a dedicated platform for each new car is no longer possible. This is why the GENIVI alliance was founded on March 2nd, 2009 with the goal of establishing an open platform for the automotive in-vehicle infotainment industry.GENIVI's strategy is to use Moblin as the baseline code within its reference implementation. Moblin is a Linux-based distribution designed for mobile devices and can perfectly be used in embedded devices such as those targeted by the infotainment industry.In this paper we experiment the real-time performances of Moblin as a standalone operating system and show how those performances can be improved by means of adding some customized real- time extensions. The main contribution of this work is to outline how those extensions are in fact necessary to comply with the real-time constraints required by automotive hosts on which infotainment applications are embedded

Pathophysiological role of prostanoids in coagulation of the portal venous system in liver cirrhosis

BACKGROUND: Prostanoids are important regulators of platelet aggregation and thrombotic arterial diseases. Their involvement in the development of portal vein thrombosis, frequent in decompensated liver cirrhosis, is still not investigated. METHODS: Therefore, we used pro-thrombotic venous milieu generation by bare metal stent transjugular intrahepatic portosystemic shunt insertion, to study the role of prostanoids in decompensated liver cirrhosis. Here, 89 patients receiving transjugular intrahepatic portosystemic shunt insertion were included in the study, and baseline levels of thromboxane B2, prostaglandin D2 and prostaglandin E2 were measured in the portal and the hepatic vein. RESULTS: While the hepatic vein contained higher levels of thromboxane B2 than the portal vein, levels of prostaglandin E2 and D2 were higher in the portal vein (all P<0.0001). Baseline concentrations of thromboxane B2 in the portal vein were independently associated with an increase of portal hepatic venous pressure gradient during short term follow-up, as an indirect sign of thrombogenic potential (multivariable P = 0.004). Moreover, severity of liver disease was inversely correlated with portal as well as hepatic vein levels of prostaglandin D2 and E2 (all P<0.0001). CONCLUSIONS: Elevated portal venous thromboxane B2 concentrations are possibly associated with the extent of thrombogenic potential in patients with decompensated liver cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03584204

Sarcopenia predicts reduced liver growth and reduced resectability in patients undergoing portal vein embolization before liver resection - A DRAGON collaborative analysis of 306 patients

Background: After portal vein embolization (PVE) 30% fail to achieve liver resection. Malnutrition is a modifiable risk factor and can be assessed by radiological indices. This study investigates, if sarcopenia affects resectability and kinetic growth rate (KGR) after PVE. Methods: A retrospective study was performed of the outcome of PVE at 8 centres of the DRAGON collaborative from 2010 to 2019. All malignant tumour types were included. Sarcopenia was defined using gender, body mass and skeletal muscle index. First imaging after PVE was used for liver volumetry. Primary and secondary endpoints were resectability and KGR. Risk factors impacting liver growth were assessed in a multivariable analysis. Results: Eight centres identified 368 patients undergoing PVE. 62 patients (17%) had to be excluded due to unavailability of data. Among the 306 included patients, 112 (37%) were non-sarcopenic and 194 (63%) were sarcopenic. Sarcopenic patients had a 21% lower resectability rate (87% vs. 66%, p &lt; 0.001) and a 23% reduced KGR (p = 0.02) after PVE. In a multivariable model dichotomized for KGR ≥2.3% standardized FLR (sFLR)/week, only sarcopenia and sFLR before embolization correlated with KGR. Conclusion: In this largest study of risk factors, sarcopenia was associated with reduced resectability and KGR in patients undergoing PVE.</p

Regulation of the DLC3 tumor suppressor by a novel phosphoswitch.

Deleted in liver cancer 3 (DLC3) is a Rho GTPase-activating protein (RhoGAP) that plays a crucial role in maintaining adherens junction integrity and coordinating polarized vesicle transport by modulating Rho activity at the plasma membrane and endomembranes. By employing bioinformatical sequence analysis, in vitro experiments, and in cellulo assays we here identified a polybasic region (PBR) in DLC3 that facilitates the association of the protein with cellular membranes. Within the PBR, we mapped two serines whose phosphorylation can alter the electrostatic character of the region. Consequently, phosphomimetic mutations of these sites impaired the membrane association of DLC3. Furthermore, we found a new PBR-dependent localization of DLC3 at the midbody region, where the protein locally controlled Rho activity. Here, the phosphorylation-dependent regulation of DLC3 appeared to be required for proper cytokinesis. Our work thus provides a novel mechanism for spatiotemporal termination of Rho signaling by the RhoGAP protein DLC3

A Global Strategy for Ecologically Sustainable Transport and other Linear Infrastructure

The current Global Strategy for Ecologically Sustainable Transport and other Linear Infrastructure primarily sets up the objectives and principles for governments and organizations for mainstreaming biodiversity and ecological connectivity on transport infrastructure development. Additionally, it addresses the overall framework of stakeholders who must be engaged as key players in: • launching proactive policies, • establishing appropriate legal frameworks, • supporting better planning, • promoting multi-sector cooperation, and • encouraging innovative science-based solutions. We consider this as a living document as future versions may integrate additional elements with regards to governance, policy, and financing, in the attempt to develop a common comprehensive language and grounds for cooperation. This “Global Strategy” has been developed by an international working group coordinated by IENE and supported by an international coalition formed from the international conferences on transport and ecology and conservation organisations as IENE, ICOET, ANET, ACLIE, WWF and IUCN. The working group is drawn from global experts in transport and ecology and aims to work towards finding a ‘win-win’ solution for securing mainstreaming biodiversity and ecological connectivity and avoiding, mitigating, or compensating ecosystems’ fragmentation during transport infrastructure development or adaptation. This Strategy builds upon five years of development of the guidelines “International Guidance for Ecologically - Friendly Linear Infrastructure (IGELI)” initiated at the ICOET 2015 conference in North Carolina, USA. IGELI was an international debate with experts from all over the world continued during workshops held at the international conferences of IENE (Lyon, France, 2016 and Eindhoven, Holland, 2018), ICOET (Salt Lake City, USA, 2017 and Sacramento, USA, 2019), IUCN (Hawaii, USA, 2016) and ACLIE (Kruger National Park, South Africa, 2019). Summarising the Decision 14/3 on mainstreaming of biodiversity in the energy and mining, infrastructure, manufacturing, and processing sectors (CBD/ COP/DEC/14/3/30 November 2018) of 14th COP CBD (Sharm El Sheikh, Egypt, Nov 2018) (Convention on Biological Diversity 2018), the international coalition of the working group, initiated to promote the Strategy at the CBD COP 15 in China. We hope, this Strategy provides a useful tool and roadmap for promoting the urgent need of supporting biodiversity conservation and securing ecological connectivity at all scales of governance, policies, planning and implementation of transport projects internationally. The creation of an International Observatory for monitoring the fragmentation status globally as an important threat for biodiversity loss is proposed as a common ambition of the working group members and their organizations.IENE, ICOET, ANET, ACLIE, WWF, IUCN, WWF, WCPA, Connectivity Conservation Specialist Grou

Observing the Evolution of the Universe

How did the universe evolve? The fine angular scale (l>1000) temperature and polarization anisotropies in the CMB are a Rosetta stone for understanding the evolution of the universe. Through detailed measurements one may address everything from the physics of the birth of the universe to the history of star formation and the process by which galaxies formed. One may in addition track the evolution of the dark energy and discover the net neutrino mass. We are at the dawn of a new era in which hundreds of square degrees of sky can be mapped with arcminute resolution and sensitivities measured in microKelvin. Acquiring these data requires the use of special purpose telescopes such as the Atacama Cosmology Telescope (ACT), located in Chile, and the South Pole Telescope (SPT). These new telescopes are outfitted with a new generation of custom mm-wave kilo-pixel arrays. Additional instruments are in the planning stages.Comment: Science White Paper submitted to the US Astro2010 Decadal Survey. Full list of 177 author available at http://cmbpol.uchicago.ed

Body mass index influences the response to infliximab in ankylosing spondylitis

INTRODUCTION: The excess of adipose tissue in obese individuals may have immunomodulating properties and pharmacokinetic consequences. The aim of this study was to determine whether body mass index (BMI) affects response to infliximab (IFX) in ankylosing spondylitis (AS) patients. METHODS: In 155 patients retrospectively included with active AS, the BMI was calculated before initiation of IFX treatment (5 mg/kg intravenously). After 6 months of treatment, changes from baseline in BASDAI, Visual Analogue Scale (VAS) pain, C-reactive protein (CRP) level, and total dose of nonsteroidal antiinflammatory drug (NSAID) were dichotomized with a threshold corresponding to a decrease of 50% of initial level of the measure, into binary variables assessing response to IFX (BASDAI50, VAS50, CRP50, NSAID50). Whether the BMI was predictive of the response to IFX therapy according to these definitions was assessed with logistic regression. RESULTS: Multivariate analysis found that a higher BMI was associated with a lower response for BASDAI50 (P = 0.0003; OR, 0.87; 95% CI (0.81 to 0.94)), VAS50 (P < 0.0001; OR, 0.87; 95% CI (0.80 to 0.93)); CRP50 (P = 0.0279; OR, 0.93; 95% CI (0.88 to 0.99)), and NSAID50 (P = 0.0077; OR, 0.91; 95% CI (0.85 to 0.97)), criteria. According to the three WHO BMI categories, similar results were found for BASDAI50 (77.6%, 48.9%, and 26.5%; P < 0.0001), VAS50 (72.6%, 40.4%, and 16.7%; P < 0.0001); CRP50 (87.5%, 65.7%, and 38.5%; P = 0.0001), and NSAID50 (63.2%, 51.5%, and 34.6%; P = 0.06). CONCLUSIONS: This study provides the first evidence that a high BMI negatively influences the response to IFX in AS. Further prospective studies, including assessment of the fat mass, pharmacokinetics, and adipokines dosages are mandatory to elucidate the role of obesity in AS IFX response

Route knowledge and configural knowledge in typical and atypical development: a comparison of sparse and rich environments

Background: Individuals with Down syndrome (DS) and individuals with Williams syndrome (WS) have poor navigation skills, which impact their potential to become independent. Two aspects of navigation were investigated in these groups, using virtual environments (VE): route knowledge (the ability to learn the way from A to B by following a fixed sequence of turns) and configural knowledge (knowledge of the spatial relationships between places within an environment). Methods: Typically developing (TD) children aged 5 to 11 years (N = 93), individuals with DS (N = 29) and individuals with WS (N = 20) were presented with a sparse and a rich VE grid maze. Within each maze, participants were asked to learn a route from A to B and a route from A to C before being asked to find a novel shortcut from B to C. Results: Performance was broadly similar across sparse and rich mazes. The majority of participants were able to learn novel routes, with poorest performance in the DS group, but the ability to find a shortcut, our measure of configural knowledge, was limited for all three groups. That is, 59 % TD participants successfully found a shortcut, compared to 10 % participants with DS and 35 % participants with WS. Differences in the underlying mechanisms associated with route knowledge and configural knowledge and in the developmental trajectories of performance across groups were observed. Only the TD participants walked a shorter distance in the last shortcut trial compared to the first, indicative of increased configural knowledge across trials. The DS group often used an alternative strategy to get from B to C, summing the two taught routes together. Conclusions: Our findings demonstrate impaired configural knowledge in DS and in WS, with the strongest deficit in DS. This suggests that these groups rely on a rigid route knowledge based method for navigating and as a result are likely to get lost easily. Route knowledge was also impaired in both DS and WS groups and was related to different underlying processes across all three groups. These are discussed with reference to limitations in attention and/or visuo-spatial processing in the atypical groups