Primary liver cancer is more aggressive in HIV-HCV coinfection than in HCV infection. A prospective study (ANRS CO13 Hepavih and CO12 Cirvir)

OBJECTIVE: Since HAART, primary liver cancer has emerged as an increasing cause of morbidity and mortality in patients with HIV infection. Our aim was to compare characteristics and outcome of primary liver cancer according to HIV status in HCV cirrhotic patients submitted to periodic ultrasonographic surveillance. METHODS: All patients with primary liver cancer and cirrhosis were selected from two prospective cohorts (ANRS CO12 Cirvir, viral cirrhosis, n=1081; ANRS CO13 Hepavih, HIV-HCV coinfection, n=1175). Cirrhosis was diagnosed by liver biopsy in monoHCV group and biopsy and/or non-invasive tests in HIV-HCV group. Ultrasonographic surveillance was performed every 6 months. Diagnosis of primary liver cancer was established according to EASL-AASLD guidelines. RESULTS: Primary liver cancer was diagnosed in 32 patients, 16 in each group, and corresponded to hepatocellular carcinoma in all except for two cholangiocarcinomas in HIV-HCV patients. Ultrasonographic follow-up was similar (median time since last ultrasonographic without focal lesion: 237 days in HIV-HCV group (n=12) versus 208 days in HCV group, NS). At primary liver cancer diagnosis HIV-HCV patients were markedly younger (48 vs. 60 yrs, P<0.001), primary liver cancer was more advanced in HIV-HCV patients (single nodule: 43% vs. 75%, P=0.07; mean diameter of main nodule: 24 vs. 16 mm, P=0.006; portal obstruction: 3 vs. 0). Curative treatment was performed in four HIV-HCV patients versus 11 HCV patients (P=0.017). During follow-up, 10 HIV-HCV patients died versus only one HCV patient (P=0.0005). CONCLUSIONS: This result suggests more aggressiveness for tumors in HIV infected patients and, if confirmed, could result in shortening the length between ultrasonographic examinations

A novel, integrated in vitro carcinogenicity test to identify genotoxic and non-genotoxic carcinogens using human lymphoblastoid cells

Human exposure to carcinogens occurs via a plethora of environmental sources, with 70–90% of cancers caused by extrinsic factors. Aberrant phenotypes induced by such carcinogenic agents may provide universal biomarkers for cancer causation. Both current in vitro genotoxicity tests and the animal-testing paradigm in human cancer risk assessment fail to accurately represent and predict whether a chemical causes human carcinogenesis. The study aimed to establish whether the integrated analysis of multiple cellular endpoints related to the Hallmarks of Cancer could advance in vitro carcinogenicity assessment. Human lymphoblastoid cells (TK6, MCL-5) were treated for either 4 or 23 h with 8 known in vivo carcinogens, with doses up to 50% Relative Population Doubling (maximum 66.6 mM). The adverse effects of carcinogens on wide-ranging aspects of cellular health were quantified using several approaches; these included chromosome damage, cell signalling, cell morphology, cell-cycle dynamics and bioenergetic perturbations. Cell morphology and gene expression alterations proved particularly sensitive for environmental carcinogen identification. Composite scores for the carcinogens’ adverse effects revealed that this approach could identify both DNA-reactive and non-DNA reactive carcinogens in vitro. The richer datasets generated proved that the holistic evaluation of integrated phenotypic alterations is valuable for effective in vitro risk assessment, while also supporting animal test replacement. Crucially, the study offers valuable insights into the mechanisms of human carcinogenesis resulting from exposure to chemicals that humans are likely to encounter in their environment. Such an understanding of cancer induction via environmental agents is essential for cancer prevention

The Effect of Tear Supplementation on Ocular Surface Sensations during the Interblink Interval in Patients with Dry Eye.

PURPOSE: To investigate the characteristics of ocular surface sensations and corneal sensitivity during the interblink interval before and after tear supplementation in dry eye patients. METHODS: Twenty subjects (41.88+/-14.37 years) with dry eye symptoms were included in the dry eye group. Fourteen subjects (39.13+/-11.27 years) without any clinical signs and/or symptoms of dry eye were included in the control group. Tear film dynamics was assessed by non-invasive tear film breakup time (NI-BUT) in parallel with continuous recordings of ocular sensations during forced blinking. Corneal sensitivity to selective stimulation of corneal mechano-, cold and chemical receptors was assessed using a gas esthesiometer. All the measurements were made before and 5 min after saline and hydroxypropyl-guar (HP-guar) drops. RESULTS: In dry eye patients the intensity of irritation increased rapidly after the last blink during forced blinking, while in controls there was no alteration in the intensity during the first 10 sec followed by an exponential increase. Irritation scores were significantly higher in dry eye patients throughout the entire interblink interval compared to controls (p0.05). CONCLUSION: Ocular surface irritation responses due to tear film drying are considerably increased in dry eye patients compared to normal subjects. Although tear supplementation improves the protective tear film layer, and thus reduce unpleasant sensory responses, the rapid rise in discomfort is still maintained and might be responsible for the remaining complaints of dry eye patients despite the treatment

Late-phase melt progression experiment: MP-2. Results and analysis

In-pile experiments addressing late-phase processes in Light Water Reactors (LWRs) were performed in the Annular Core Research Reactor (ACRR) at Sandia National Laboratories. Melt Progression (MP) experiments were designed to provide information to develop and verify computer models for analysis of LWR core damage in severe accidents. Experiments examine the formation and motion of ceramic molten pools in disrupted reactor core regions. The MP-2 experiment assembly consisted of: (1) a rubble bed of enriched UO{sub 2} and ZrO{sub 2} simulating severely disrupted reactor core regions, (2) a ceramic/metallic crust representing blockage formed by early phase melting, relocation, and refreezing of core components, and (3) an intact rod stub region that remained in place below the blockage region. The test assembly was fission heated in the central cavity of the ACRR at an average rate of about 0.2 KA, reaching a peak molten pool temperature around 3400 K. Melting of the debris bed ceramic components was initiated near the center of the bed. The molten material relocated downward, refreezing to form a ceramic crust near the bottom of the rubble bed. As power levels were increased, the crust gradually remelted and reformed at progressively lower positions in the bed until late in the experiment when it penetrated into and attacked the ceramic/metallic blockage. The metallic components of the blockage region melted and relocated to the bottom of the intact rod stub region before the ceramic melt penetrated the blockage region from above. The ceramic pool penetrated halfway into the blockage region by the end of the experiment. Measurements of thermal response and material relocation are compared to the results of the computer simulations. Postexperiment examination of the assembly with the associated material interactions and metallurgy are also discussed in detail with the analyses and interpretation of results. 16 refs., 206 figs., 24 tabs

European Stroke Organisation (ESO) Guidelines on Management of Unruptured Intracranial Aneurysms

Unruptured intracranial aneurysms (UIA) occur in around 3% of the population. Important management questions concern if and how to perform preventive UIA occlusion; if, how and when to perform follow up imaging and non-interventional means to reduce the risk of rupture. Using the Standard Operational Procedure of ESO we prepared guidelines according to GRADE methodology. Since no completed randomised trials exist, we used interim analyses of trials, and meta-analyses of observational and case-control studies to provide recommendations to guide UIA management. All recommendations were based on very low evidence. We suggest preventive occlusion if the estimated 5-year rupture risk exceeds the risk of preventive treatment. In general, we cannot recommend endovascular over microsurgical treatment, but suggest flow diverting stents as option only when there are no other low-risk options for UIA repair. To detect UIA recurrence we suggest radiological follow up after occlusion. In patients who are initially observed, we suggest radiological monitoring to detect future UIA growth, smoking cessation, treatment of hypertension, but not treatment with statins or acetylsalicylic acid with the indication to reduce the risk of aneurysm rupture. Additionally, we formulated 15 expert-consensus statements. All experts suggest to assess UIA patients within a multidisciplinary setting (neurosurgery, neuroradiology and neurology) at centres consulting >100 UIA patients per year, to use a shared decision-making process based on the team recommendation and patient preferences, and to repair UIA only in centres performing the proposed treatment in >30 patients with (ruptured or unruptured) aneurysms per year per neurosurgeon or neurointerventionalist. These UIA guidelines provide contemporary recommendations and consensus statement on important aspects of UIA management until more robust data come available.info:eu-repo/semantics/publishedVersio

CFD analysis of coolant mixing in VVER-1000/V320 reactor pressure vessel

This study presents a code-to-code and model-to-model comparison of coolant mixing in the VVER-1000/V320 Kozloduy Unit 6 nuclear power plant using Computational Fluid Dynamics (CFD). Four different CFD codes were used to simulate coolant mixing in the reactor vessel, namely ANSYS Fluent, ANSYS CFX, TrioCFD, and STAR-CCM+. Two different approaches were used to model the upper plenum, while a single simplified model was used for the reactor pressure vessel. The simulations were performed for VVER-1000 coolant transient benchmark (V1000CT-2) mixing exercise. The results were compared between the different CFD codes and models to assess the accuracy and consistency of the simulations with the available experimental data. Overall, the results showed good agreement between the different CFD codes and models, with minor differences observed in some cases. The simplified models were found to be sufficient for predicting the overall coolant mixing patterns observed in the reactor vessel, provided additional insights into the local flow structures and mixing characteristics. This study demonstrates the applicability and reliability of CFD simulations for coolant mixing analysis in VVER-1000/V320 nuclear power plants

Evidence of gating in hundred nanometer diameter pores: an experimental and theoretical study

We report on the observation of an unexpected gating mechanism at the 100 nm scale on track-etched polycarbonate membranes. Transport measurements of methyl viologen performed by absorption spectroscopy under various pH conditions demonstrated that perfect gating was achieved for 100 nm diameter pores at pH 2, while the positively charged molecular ions moved through the membrane according to diffusion laws at pH 5. An oppositely charged molecular ion, naphthalene disulfonate, in the same membrane, showed the opposite trend: diffusion of the negative ion at pH 2 and perfect gating at pH 5. The influence of parameters such as ionic strength and membrane surface coating were also investigated. A theoretical study of the system shows that at this larger length scale the magnitude of the electric field in the vicinity of the pores is too small to account for the experimental observations, rather, it is the surface trapping of the mobile ion (Cl{sup -} or Na{sup +}) which gives rise to the gating phenomena. This surprising effect might have potential applications for high-throughput separation of large molecules and bio-organisms