Buoyancy and local friction effects on rockfill settlements: A discrete modelling

AbstractMeasured displacements in the upstream shell of rockfill dams show some settlements which can reach a few meters with water levels changes, especially during the first impounding, whereas downstream displacements are smaller. Complementary phenomena are responsible for rockfill collapse due to wetting. Here we numerically investigate the effects of buoyancy forces and the decrease in the coefficient of friction with water on a rockfill column maintained by vertical rigid walls and progressively filled with water. Numerical simulations of the settlements of the rockfill column, using the Contact Dynamics method, are presented. Buoyancy forces seem to have only a negligible influence on the granular pile. Decrease in the friction angle of the rock with water induces rearrangements of the medium, all the more as the decrease is significant. These dynamic rearrangements exhibit an irregular temporal evolution of the granular medium which can be characterized by a phenomenon of local “crisis”. Analysis of the settlements shows that these two combined effects are not the major cause of the settlements observed in rockfill dams and that they cannot in particular explain the settlements

Monitoring alkylphenols in water using the polar organic chemical integrative sampler (POCIS): determining sampling rates via the extraction of PES membranes and Oasis beads

Polar organic chemical integrative samplers (POCIS) have previously been used to monitor alkylphenol (AP) contamination in water and produced water. However, only the sorbent receiving phase of the POCIS (Oasis beads) is traditionally analyzed, thus limiting the use of POCIS for monitoring a range of APs with varying hydrophobicity. Here a “pharmaceutical” POCIS was calibrated in the laboratory using a static renewal setup for APs (from 2-ethylphenol to 4-n-nonylphenol) with varying hydrophobicity (log Kow between 2.47 and 5.76). The POCIS sampler was calibrated over its 28 day integrative regime and sampling rates (Rs) were determined. Uptake was shown to be a function of AP hydrophobicity where compounds with log Kow < 4 were preferentially accumulated in Oasis beads, and compounds with log Kow > 5 were preferentially accumulated in the PES membranes. A lag phase (over a 24 h period) before uptake in to the PES membranes occurred was evident. This work demonstrates that the analysis of both POCIS phases is vital in order to correctly determine environmentally relevant concentrations owing to the fact that for APs with log Kow ≤ 4 uptake, to the PES membranes and the Oasis beads, involves different processes compared to APs with log Kow ≥ 4. The extraction of both the POCIS matrices is thus recommended in order to assess the concentration of hydrophobic APs (log Kow ≥ 4), as well as hydrophilic APs, most effectively. © 2017 Elsevier Lt

A mass closure and PMF source apportionment study on the sub-micron sized aerosol fraction at urban sites in Italy

Sub-micron sized particles are of increasing concern owing to their effects on human health and on the environment. Up to now there are still very few studies on PM1 (i.e. particulate matter with aerodynamic diameter smaller than 1 mm) chemical characterisation; the sub-micron sized fraction is not under regulations although it is of interest because it is almost exclusively associated to anthropogenic sources. To perform the first large-scale assessment of sub-micron sized aerosol concentrations, composition and sources, two monitoring campaigns at three urban sites in Italy were carried out during the wintertime and summertime of 2004. Chemical characterisation (elements, soluble ionic fraction, elemental and organic carbon) was carried out on PM1 samples: major contributions were due to organic matter (about 30% in summer and 50% in winter) and ammonium sulphate (about 10% in winter and 40% in summer). During the cold season, nitrates also contributed up to 30% in Milan (lower contributions were registered at the other two urban sites). Chemical mass closure was achieved with an unaccounted mass in the range 14\u201322%. Positive Matrix Factorisation (PMF) was applied to identify the major submicron sized particles\u2019 sources

Early-life nicotine or cotinine exposure produces long-lasting sleep alterations and downregulation of hippocampal corticosteroid receptors in adult mice

Early-life exposure to environmental toxins like tobacco can permanently re-program body structure and function. Here, we investigated the long-term effects on mouse adult sleep phenotype exerted by early-life exposure to nicotine or to its principal metabolite, cotinine. Moreover, we investigated whether these effects occurred together with a reprogramming of the activity of the hippocampus, a key structure to coordinate the hormonal stress response. Adult male mice born from dams subjected to nicotine (NIC), cotinine (COT) or vehicle (CTRL) treatment in drinking water were implanted with electrodes for sleep recordings. NIC and COT mice spent significantly more time awake than CTRL mice at the transition between the rest (light) and the activity (dark) period. NIC and COT mice showed hippocampal glucocorticoid receptor (GR) downregulation compared to CTRL mice, and NIC mice also showed hippocampal mineralocorticoid receptor downregulation. Hippocampal GR expression significantly and inversely correlated with the amount of wakefulness at the light-to-dark transition, while no changes in DNA methylation were found. We demonstrated that early-life exposure to nicotine (and cotinine) concomitantly entails long-lasting reprogramming of hippocampal activity and sleep phenotype suggesting that the adult sleep phenotype may be modulated by events that occurred during that critical period of life

A 3D‐Bioprinted Vascularized Glioblastoma‐on‐a‐Chip for Studying the Impact of Simulated Microgravity as a Novel Pre‐Clinical Approach in Brain Tumor Therapy

Glioblastoma multiforme (GBM) is one of the most aggressive malignant brain tumors and urgently requires the development of new therapeutic strategies. In this study, an innovative hybrid in vitro vascularized GBM-on-a-chip model is presented as a strategic integration of microfluidics and 3D bioprinting technologies. The system can recreate the compartmentalized brain tumor microenvironment, comprising the functional blood brain barrier (BBB) and the adjacent 3D perivascular tumor niche, by selectively mimicking physiological shear stress and cell–cell, cell–matrix mechanical interaction. The GBM-on-a-chip model was evaluated under simulated microgravity (µG) condition as a form of mechanical unloading showing a significant cell morphological and mechanotransduction response thereby indicating that gravitational forces play an important role in glioblastoma mechanical regulation. The proposed GBM-on-a-chip represents a meaningful biological tool for further research in cancer mechanobiology and pre-clinical approach in brain tumor therapy

Consensus guidelines on the construct validity of rodent models of restless legs syndrome.

Our understanding of the causes and natural course of restless legs syndrome (RLS) is incomplete. The lack of objective diagnostic biomarkers remains a challenge for clinical research and for the development of valid animal models. As a task force of preclinical and clinical scientists, we have previously defined face validity parameters for rodent models of RLS. In this article, we establish new guidelines for the construct validity of RLS rodent models. To do so, we first determined and agreed on the risk, and triggering factors and pathophysiological mechanisms that influence RLS expressivity. We then selected 20 items considered to have sufficient support in the literature, which we grouped by sex and genetic factors, iron-related mechanisms, electrophysiological mechanisms, dopaminergic mechanisms, exposure to medications active in the central nervous system, and others. These factors and biological mechanisms were then translated into rodent bioequivalents deemed to be most appropriate for a rodent model of RLS. We also identified parameters by which to assess and quantify these bioequivalents. Investigating these factors, both individually and in combination, will help to identify their specific roles in the expression of rodent RLS-like phenotypes, which should provide significant translational implications for the diagnosis and treatment of RLS

Prospective study of carmustine wafers in combination with 6-month metronomic temozolomide and radiation therapy in newly diagnosed glioblastoma: preliminary results

Object. Locoregional chemotherapy with carmustine wafers, positioned at surgery and followed by radiation therapy, has been shown to prolong survival in patients with newly diagnosed glioblastoma, as has concomitant radiochemotherapy with temozolomide. A combination of carmustine wafers with the Stupp treatment regimen has only been investigated in retrospective studies. Methods. In a single-institution prospective study, the authors assessed 12-month progression-free survival (PFS), toxicity, and overall survival in patients with glioblastoma treated with surgery, carmustine wafers, radiotherapy, and 6-month metronomic temozolomide chemotherapy. Thirty-five patients with de novo glioblastoma, between the ages of 18 and 70 years, and with Karnofsky Performance Scale scores of at least 70, were included in the study. Patients were followed monthly and assessed using MRI every 2 months. Results. After a median follow-up of 15 months, the median time to tumor progression was 12.5 months and median survival was 17.8 months. Due to toxicity (mostly hematological), 7 patients had to prematurely stop temozolomide treatment. Twenty-two patients developed Grade 3 CD4(+) lymphocytopenia. Three patients developed oral-esophageal candidiasis, 2 developed pneumonia, and 1 developed a dorsolumbar zoster. Early intracranial hypertension was observed in 1 patient, and 1 was treated empirically for suspected brain abscess. One patient died of Legionella pneumonia soon after repeat surgery. Conclusions. Overall, this treatment schedule produced promising results in terms of PFS without a marked increase in toxicities as compared with the Stupp regimen. However, the gain in median survival using this schedule was less clear. Only prospective comparative trials will determine whether these preliminary results will translate into a long-term survival advantage with an acceptable toxicity profile

BCNU for recurrent glioblastoma multiforme: efficacy, toxicity and prognostic factors

<p>Abstract</p> <p>Background</p> <p>The prognosis for patients with recurrent glioblastoma is still poor with a median survival between 3 and 6 months. Reports about the application of carmustine (BCNU), one of the standard chemotherapeutic drugs in the treatment of newly diagnosed glioblastoma, in the recurrent situation are rare.</p> <p>Methods</p> <p>We performed a retrospective analysis of 35 patients with recurrent or progressive glioblastoma treated with 80 mg/m²BCNU on days 1 on 3 intravenously at our department for efficacy, toxicity and prognostic factors. Progression free survival and overall survival were estimated by the Kaplan-Meier method. The influence of age, Karnofsky performance status (KPS), tumor burden, pretreatment with temozolomide (TMZ), type of surgery for initial diagnosis and number of previous relapses on outcome was analyzed in a proportional hazards regression model.</p> <p>Results</p> <p>The median age of the group was 53 years, median KPS was 70. Median progression free survival was 11 weeks (95% confidence interval [CI]: 8-15), median overall survival 22 weeks (95% CI: 18-27). The rate of adverse events, especially hematological toxicity, is relatively high, and in 3 patients treatment had to be terminated due to adverse events (one pulmonary embolism, one pulmonary fibrosis, and one severe bone marrow suppression). No influence of age, KPS, tumor burden, pre-treatment with TMZ and number of previous relapses on outcome could be demonstrated, while gross total resection prior to recurrence showed a borderline statistically significant negative impact on PFS and OS. These data compare well with historical survival figures. However prospective randomized studies are needed to evaluate BCNU efficacy against newer drugs like bevacizumab or the intensified temozolomide regime (one week on/one week off).</p> <p>Conclusion</p> <p>In summary, BCNU treatment appears to be a valuable therapeutic option for recurrent glioblastomas, where no other validated radio- and/or chemotherapy are available.</p