Incurred environmental risks and potential contamination sources in an abandoned mine site

The mineralogical characterization of Fedj Lahdoum mine wastes measured by X-ray Diffraction (XRD) and Scanning Electron Microscopy (SEM) showed the presence of the following sulfide minerals: galena (PbS), sphalerite (ZnS), pyrite (FeS2), cerussite (PbCO3) and smithsonite (ZnCO3). The wastes were stored in tailing ponds. The results showed that the concentration of metals from tailings were up to 10 460 mg.kg-1 for total Zn, 2 100 mg.kg-1 for total Pb and 62.08 mg.kg-1 for total Cd. The tailings have presented a fine unconsolidated texture that accelerated the dispersion of the particles rich in heavy metals. Geochemical analysis of soil has revealed high total contents of Pb, Zn and Cd, respectively: 3 646, 3 236 and 17 mg.kg-1. Chemical analysis of cultivated and wild plants species inside the district contain high grades in heavy metals: 708.56 mg Zn. kg-1; 16.24 mg Pb.kg-1 (Thymus vulgaris (L)); 500.44 mg Zn. kg-1, 12.44 mg Pb. kg-1 (Laurus nobilis (L)); 128.33 mg Zn. kg-1 and 22.53 mg Pb.kg-1 (Ficus (L)) and 106.73 mgZn.kg-1 (pimento). The high levels detected in soil and plants have exceeded the Tunisian and Canadian standards. These results showed that the abandoned site was contaminated by the presence of tailing dumps which were exposed to significant water and/or wind erosion. To solve this problem, we proposed an environmental desulphurization by froth flotation.Keywords: Heavy metals, mine tailings, abandoned mining-district, plant contamination

A randomized, controlled trial of the pan-PPAR agonist lanifibranor in NASH

BACKGROUND Management of nonalcoholic steatohepatitis (NASH) is an unmet clinical need. Lanifibranor is a pan-PPAR (peroxisome proliferator–activated receptor) agonist that modulates key metabolic, inflammatory, and fibrogenic pathways in the pathogenesis of NASH. METHODS In this phase 2b, double-blind, randomized, placebo-controlled trial, patients with noncirrhotic, highly active NASH were randomly assigned in a 1:1:1 ratio to receive 1200 mg or 800 mg of lanifibranor or placebo once daily for 24 weeks. The pri- mary end point was a decrease of at least 2 points in the SAF-A score (the activity part of the Steatosis, Activity, Fibrosis [SAF] scoring system that incorporates scores for ballooning and inflammation) without worsening of fibrosis; SAF-A scores range from 0 to 4, with higher scores indicating more-severe disease activity. Secondary end points included resolution of NASH and regression of fibrosis. RESULTS A total of 247 patients underwent randomization, of whom 103 (42%) had type 2 diabetes mellitus and 188 (76%) had significant (moderate) or advanced fibrosis. The percentage of patients who had a decrease of at least 2 points in the SAF-A score without worsening of fibrosis was significantly higher among those who received the 1200-mg dose, but not among those who received the 800-mg dose, of lanifibranor than among those who received placebo (1200-mg dose vs. placebo, 55% vs.33%, P = 0.007; 800-mg dose vs. placebo, 48% vs. 33%, P = 0.07). The results favored both the 1200-mg and 800-mg doses of lanifibranor over placebo for resolution of NASH without worsening of fibrosis (49% and 39%, respectively, vs. 22%), improvement in fibrosis stage of at least 1 without worsening of NASH (48% and 34%, respectively, vs. 29%), and resolution of NASH plus improvement in fibrosis stage of at least 1 (35% and 25%, respectively, vs. 9%). Liver enzyme levels decreased and the levels of the majority of lipid, inflammatory, and fibrosis biomarkers improved in the lanifibranor groups. The dropout rate for adverse events was less than 5% and was similar across the trial groups. Diarrhea, nausea, peripheral edema, anemia, and weight gain occurred more frequently with lanifibranor than with placebo. CONCLUSIONS In this phase 2b trial involving patients with active NASH, the percentage of patients who had a decrease of at least 2 points in the SAF-A score without worsening of fibrosis was significantly higher with the 1200-mg dose of lanifibranor than with placebo. These findings support further assessment of lanifibranor in phase 3 trials. (Funded by Inventiva Pharma; NATIVE ClinicalTrials.gov number, NCT0300807

Non-semisimple Lie algebras with Levi factor \frak{so}(3), \frak{sl}(2,R) and their invariants

We analyze the number N of functionally independent generalized Casimir invariants for non-semisimple Lie algebras \frak{s}\overrightarrow{% oplus}_{R}\frak{r} with Levi factors isomorphic to \frak{so}(3) and \frak{sl}(2,R) in dependence of the pair (R,\frak{r}) formed by a representation R of \frak{s} and a solvable Lie algebra \frak{r}. We show that for any dimension n >= 6 there exist Lie algebras \frak{s}\overrightarrow{\oplus}_{R}\frak{r} with non-trivial Levi decomposition such that N(\frak{s}% \overrightarrow{oplus}_{R}\frak{r}) = 0.Comment: 16 page

Casimir invariants for the complete family of quasi-simple orthogonal algebras

A complete choice of generators of the center of the enveloping algebras of real quasi-simple Lie algebras of orthogonal type, for arbitrary dimension, is obtained in a unified setting. The results simultaneously include the well known polynomial invariants of the pseudo-orthogonal algebras $so(p,q)$, as well as the Casimirs for many non-simple algebras such as the inhomogeneous $iso(p,q)$, the Newton-Hooke and Galilei type, etc., which are obtained by contraction(s) starting from the simple algebras $so(p,q)$. The dimension of the center of the enveloping algebra of a quasi-simple orthogonal algebra turns out to be the same as for the simple $so(p,q)$ algebras from which they come by contraction. The structure of the higher order invariants is given in a convenient "pyramidal" manner, in terms of certain sets of "Pauli-Lubanski" elements in the enveloping algebras. As an example showing this approach at work, the scheme is applied to recovering the Casimirs for the (3+1) kinematical algebras. Some prospects on the relevance of these results for the study of expansions are also given.Comment: 19 pages, LaTe

Results from a new efficacy and safety analysis of the REGENERATE trial of obeticholic acid for treatment of pre-cirrhotic fibrosis due to non-alcoholic steatohepatitis

BACKGROUND &amp; AIMS: Obeticholic acid (OCA) is a first-in-class farnesoid X receptor agonist and antifibrotic agent in development for the treatment of pre-cirrhotic liver fibrosis due to non-alcoholic steatohepatitis (NASH). We aimed to validate the original 18-month liver biopsy analysis from the phase III REGENERATE trial of OCA for the treatment of NASH with a consensus panel analysis, provide additional histology data in a larger population, and evaluate safety from &gt;8,000 total patient-years' exposure with nearly 1,000 participants receiving study drug for &gt;4 years.METHODS: Digitized whole-slide images were evaluated independently by panels of three pathologists using the NASH Clinical Research Network scoring system. Primary endpoints were (1) ≥1 stage improvement in fibrosis with no worsening of NASH or (2) NASH resolution with no worsening of fibrosis. Safety was assessed by laboratory values and adverse events.RESULTS: Prespecified efficacy analyses included 931 participants. The proportion of participants achieving a ≥1 stage improvement in fibrosis with no worsening of NASH was 22.4% for OCA 25 mg vs. 9.6% for placebo (p &lt;0.0001). More participants receiving OCA 25 mg vs. placebo achieved NASH resolution with no worsening of fibrosis (6.5% vs. 3.5%, respectively; p = 0.093). Histology data in a larger population of 1,607 participants supported these results. Safety data included 2,477 participants. The incidence of treatment-emergent adverse events (TEAEs), serious TEAEs, and deaths was not substantively different across treatment groups. Pruritus was the most common TEAE. Rates of adjudicated hepatic, renal, and cardiovascular events were low and similar across treatment groups.CONCLUSIONS: These results confirm the antifibrotic effect of OCA 25 mg. OCA was generally well tolerated over long-term dosing. These data support a positive benefit:risk profile in patients with pre-cirrhotic liver fibrosis due to NASH.IMPACT AND IMPLICATIONS: Patients with non-alcoholic steatohepatitis (NASH) often have liver scarring (fibrosis), which causes an increased risk of liver-related illness and death. Preventing progression of fibrosis to cirrhosis or reversing fibrosis are the main goals of drug development for NASH. In this clinical trial of obeticholic acid (OCA) in patients with NASH (REGENERATE), we reaffirmed our previous results demonstrating that OCA was superior to placebo in improving fibrosis using a more rigorous consensus panel analysis of liver biopsies taken at month 18. We also showed that OCA treatment resulted in dose-dependent reductions of serum liver biochemistries and liver stiffness measurements compared with placebo, even in participants in whom histologic fibrosis did not change at 18 months, providing evidence that the benefit of OCA extends beyond what is captured by the ordinal NASH CRN scoring system. OCA was well tolerated with a favorable safety profile supporting a positive benefit: risk profile in patients with pre-cirrhotic liver fibrosis due to NASH.</p

Metamaterial superlenses operating at visible wavelength for imaging applications

© 2018 The Authors. Published by Nature. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1038/s41598-018-33572-yIn this paper, a novel design for a metamaterial lens (superlens) based on a Photonic Crystal (PC) operating at visible wavelengths is reported. The proposed superlens consist of a gallium phosphide (GaP) dielectric slab waveguide with a hexagonal array of silver rods embedded within the GaP dielectric. In-house 2DFDTD numerical method is used to design and optimize the proposed superlens. Several superlenses are designed and integrated within a same dielectric platform, promoting the proof-of-concept (POC) of possible construction of an array of superlenses (or sub-lenses to create an M-Lens) for light field imaging applications. It is shown that the concavity of the superlens and positioning of each sub-lens within the array strongly affects the performances of the image in terms of resolution. Defects and various geometrical shapes are introduced to construct and optimize the proposed superlenses and increase the quality of the image resolution. It is shown that the orientation of the active region (ellipse) along x and y axis has tremendous influence on the quality of image resolution. In order to investigate the performance characteristics of the superlenses, transmitted power is calculated using 2D FDTD for image projections at various distances (in x and y plane). It is also shown, how the proposed superlens structures could be fabricated using standard micro fabrication techniques such as electron beam lithography, inductively coupled Reactive ion etching, and glancing angle evaporation methods. To the best of our knowledge, these are the first reported POC of superlenses, integrated in a monolithic platform suitable for high imaging resolution that can be used for light field imaging applications at visible wavelength. The proposed superlenses (integrated in a single platform M-Lens) will have tremendous impact on imaging applications

A randomized, placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis

The aim of this study was to evaluate cenicriviroc (CVC), a dual antagonist of C-C chemokine receptor types 2 and 5, for treatment of nonalcoholic steatohepatitis (NASH) with liver fibrosis. A randomized, double-blind, multinational phase 2b study enrolled subjects with NASH, a nonalcoholic fatty liver disease activity score [NAS] ≥4, and liver fibrosis (stages 1–3, NASH Clinical Research Network) at 81 clinical sites. Subjects (N = 289) were randomly assigned CVC 150 mg or placebo. Primary outcome was ≥2-point improvement in NAS and no worsening of fibrosis at year 1. Key secondary outcomes were: resolution of steatohepatitis and no worsening of fibrosis; improvement in fibrosis by ≥1 stage and no worsening of steatohepatitis. Biomarkers of inflammation and adverse events were assessed. Full study recruitment was achieved. The primary end point of NAS improvement in the intent-to-treat population and resolution of steatohepatitis was achieved in a similar proportion of subjects on CVC (N = 145) and placebo (N = 144) (16% vs 19%, P = 0.52 and 8% vs 6%, P = 0.49, respectively). However, the fibrosis end point was met in significantly more subjects on CVC than placebo (20% vs 10%; P = 0.02). Treatment benefits were greater in those with higher disease activity and fibrosis stage at baseline. Biomarkers of systemic inflammation were reduced with CVC. Safety and tolerability of CVC were comparable to placebo. Conclusions: After 1 year of CVC treatment, twice as many subjects achieved improvement in fibrosis and no worsening of steatohepatitis compared with placebo. Given the urgent need to develop antifibrotic therapies in NASH, these findings warrant phase 3 evaluation