Coupled ‘storm-flood’ depositional model: application to the Miocene–Modern Baram Delta Province, north-west Borneo

The Miocene to Modern Baram Delta Province is a highly efficient source to sink system that has accumulated 9 to 12 km of coastal-deltaic to shelf sediments over the past 15 Myr. Facies analysis based on ca 1 km of total vertical outcrop stratigraphy, combined with subsurface geology and sedimentary processes in the present-day Baram Delta Province, suggests a ‘storm-flood’ depositional model comprising two distinct periods: (i) fair-weather periods are dominated by alongshore sediment reworking and coastal sand accumulation; and (ii) monsoon-driven storm periods are characterised by increased wave energy and offshore-directed downwelling storm flow that occur simultaneously with peak fluvial discharge caused by storm-precipitation (‘storm-floods’). The modern equivalent environment has the following characteristics: (i) humid-tropical monsoonal climate; (ii) narrow (ca <100 km) and steep (ca 1°), densely vegetated, coastal plain; (iii) deep tropical weathering of a mudstone-dominated hinterland; (iv) multiple independent, small to moderate-sized (102 to 105 km2) drainage basins; (v) predominance of river-mouth bypassing; and (vi) supply-dominated shelf. The ancient, proximal part of this system (the onshore Belait Formation) is dominated by strongly cyclical sandier-upward successions (metre to decametre-scale) comprising (from bottom to top): (i) finely laminated mudstone with millimetre-scale silty laminae; (ii) heterolithic sandstone-mudstone alternations (centimetre to metre-scale); and (iii) sharp-based, swaley cross-stratified sandstone beds and bedsets (metre to decimetre-scale). Gutter casts (decimetre to metre-scale) are widespread, they are filled with swaley cross-stratified sandstone and their long-axes are oriented perpendicular to the palaeo-shoreline. The gutter casts and other associated waning-flow event beds suggest that erosion and deposition was controlled by high-energy, offshore-directed, oscillatory-dominated, sediment-laden combined flows within a shoreface to delta front setting. The presence of multiple river mouths and exceptionally high rates of accommodation creation (characteristic of the Neogene to Recent Baram Delta Province; up to 3000 m/Ma), in a ‘storm-flood’ dominated environment, resulted in a highly efficient and effective offshore-directed sediment transport system

Multi tyrosine kinase inhibitor dasatinib as novel cause of severe pre-capillary pulmonary hypertension?

<p>Abstract</p> <p>Background</p> <p>Pulmonary hypertension (PH) is a life-threatening disease with poor prognosis. Encouraging efforts have been made to target the main vasoproliferative aspects of the disease. Promising emerging therapeutics are tyrosine kinase inhibitors such as imatinib.</p> <p>Case presentation</p> <p>Here, we discuss the relevance of previously published cases and add another well-characterised patient who developed pre-capillary PH under long-term therapy with the multi-tyrosine kinase inhibitor dasatinib approved for therapy of chronic myeloic leukaemia (CML) and Philadelphia chromosome positive acute lymphocytic leukaemia (mean time of all patients on dasatinib: 26 months). Hence, we discuss the possibility of dasatinib itself causing PH after long-term therapy and turn specialist's attention to this possible severe side effect.</p> <p>At present, the true incidence of dasatinib-associated PH remains illusive and systematic data regarding haemodynamics are missing.</p> <p>Conclusion</p> <p>We therefore recommend systematic screening of dasatinib-treated patients for pulmonary hypertension and subsequent collection of haemodynamic data.</p

The synthetic inhibitor of Fibroblast Growth Factor Receptor PD166866 controls negatively the growth of tumor cells in culture

<p>Abstract</p> <p>Background</p> <p>Many experimental data evidence that over-expression of various growth factors cause disorders in cell proliferation. The role of the Fibroblast Growth Factors (FGF) in growth control is indisputable: in particular, FGF1 and its tyrosine kinase receptor (FGFR1) act through a very complex network of mechanisms and pathways. In this work we have evaluated the antiproliferative activity effect of PD166866, a synthetic molecule inhibiting the tyrosin kinase action of FGFR1.</p> <p>Methods</p> <p>Cells were routinely grown in Dulbecco Modified Eagle's medium supplemented with newborn serum and a penicillin-streptomycin mixture.</p> <p>Cell viability was evaluated by Mosmann assay and by trypan blue staining. DNA damage was assessed by <it>in situ </it>fluorescent staining with Terminal Deoxynucleotidyl Transferase dUTP nick end labeling (TUNEL assay).</p> <p>Assessment of oxidative stress at membrane level was measured by quantitative analysis of the intra-cellular formation of malonyl-dialdheyde (MDA) deriving from the decomposition of poly-unsaturated fatty acids.</p> <p>The expression of Poly-ADP-Ribose-Polymerase (PARP), consequent to DNA fragmentation, was evidenced by immuno-histochemistry utilizing an antibody directed against an N-terminal fragment of the enzyme.</p> <p>Results</p> <p>The bioactivity of the drug was investigated on Hela cells. Cytoxicity was assessed by the Mosmann assay and by vital staining with trypan blue. The target of the molecule is most likely the cell membrane as shown by the significant increase of the intracellular concentration of malonyl-dihaldheyde. The increase of this compound, as a consequence of the treatment with PD166866, is suggestive of membrane lipoperoxidation. The TUNEL assay gave a qualitative, though clear, indication of DNA damage. Furthermore we demonstrate intracellular accumulation of poly-ADP-ribose polymerase I. This enzyme is a sensor of nicks on the DNA strands and this supports the idea that treatment with the drug induces cell death.</p> <p>Conclusions</p> <p>Data presented in this work show that PD166866 has clear antiproliferative effects. The negative control of cell proliferation may be exerted through the activation of the apoptotic pathway. The results of experiments addressing this specific point, such as: evaluation of DNA damage, lipoperoxidation of the cell membrane and increase of expression of PARP, an enzyme directly involved in DNA repair. Results suggest that cells exposed to PD16866 undergo apoptosis. However, concomitant modes of cell death cannot be ruled out. The possible use of this drug for therapeutic purposes is discussed.</p

Infections rapportées chez 109 patients avec syndrome de Gougerot-Sjögren primaire suivis au CHU de Montpellier

International audienceIntroduction: Infections are responsible for a part of the overall mortality in primary Sjögren's syndrome patients (pSS). Our retrospective monocentric study aimed at describing infections reported in a population of pSS hospitalized patients, along with the characteristics of their disease.Methods: Patients with SS have been randomly selected from our hospital database claim, between 2009 and 2018. After careful analysis of their medical chart, only patients with pSS and fulfilling ACR/EULAR 2016 diagnosis criteria were included. We collected main clinical, biological and pathological characteristics of SS, along with all the reported infections during the follow-up. The characteristics of the disease were compared according to the presence of an infection in hospitalization.Results: In total, 109 pSS patients were included (93% of women, mean age 53.6±14.3 years, mean follow-up 8.2±8.4 years). Fifty-one percent had been exposed to hydroxychloroquine (HCQ). Seventy-eight infections were recorded in 47 (43%) patients. Twenty-five infections were recorded in hospitalization (5 in critical care) in 20 (18%) patients, whom leading causes were urinary tract (28%), pulmonary (24%), ENT (16%), and intestinal (12%) infections. pSS patients with infections in hospitalization were older, exhibited more hypocomplementemia, and were less exposed to HCQ. We found no difference in immunosuppressive treatments exposure.Conclusions: The impact of HCQ exposure on infectious risk needs further investigations. Broad vaccination campaign and tight control of sicca syndrome could lead to a better control of infection risk

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