Salinity dynamics under different water management plans coupled with sea level rise scenarios in the Red River Delta, Vietnam

In recent years, saltwater intrusion in river estuaries has become more severe and frequent worldwide. The common reasons lie in increasing freshwater withdrawal, river flow regulation and sea level rise due to global warming. In particular, the Red River Delta in northern Vietnam is facing a strong population growth worsening the pressure on freshwater resources for drinking water and irrigation needs. During the dry season, increasing conflicts and constraints in freshwater availability have already been experienced. Adverse combinations of river flow regulations and high sea levels lead to severe upstream propagations of salinity. This study takes advantage of a statistical characterization of discharges released from Hoa Binh reservoir and observed at Son Tay station, the main river flow control upstream of the river delta, along with downscaled and updated sea level rise sce- narios to estimate the future extents of saltwater intrusion under different options of water release from reser- voirs in the dry season. To do so, a 1D hydraulic model of the river delta network was implemented using MIKE11 software. The hydraulic and the quality modules were calibrated and validated with respect to the present scenario by using water stages and salinity concentrations observed in estuary branches. Sea level rise projections for 2050 and 2100 referred to RCP4.5 and RCP8.5 AR5 emission scenarios were then considered. Results show that river flow regulation can provide an effective mitigation measure. A 20–30% increase in the discharge released from the Son Tay station would be beneficial to push downstream the saltwater intrusion in the main Red River branch during the dry season. For instance, in 2050 the 1‰ salt concentration front is ex- pected to be pushed back at least 6 km when the exceeding probability of the discharge released by Son Tay station decreases from 95% to 25%

P045 THE USE OF AZATHIOPRINE FOR THE TREATMENT OF INFLAMMATORY BOWEL DISEASES IN CLINICAL PRACTICE: A MULTICENTER, RETROSPECTIVE STUDY

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Manganese concentrations in soil and settled dust in an area with historic ferroalloy production

Ferroalloy production can release a number of metals into the environment, of which manganese (Mn) is of major concern. Other elements include lead, iron, zinc, copper, chromium, and cadmium. Manganese exposure derived from settled dust and suspended aerosols can cause a variety of adverse neurological effects to chronically exposed individuals. To better estimate the current levels of exposure, this study quantified metal levels in dust collected inside homes (n=85), outside homes (n=81), in attics (n=6), and in surface soil (n=252) in an area with historic ferroalloy production. Metals contained in indoor and outdoor dust samples were quantified using inductively coupled plasma optical emission spectroscopy while attic and soil measurements were made with a XRF instrument. Mean Mn concentrations in soil (4600 μg/g) and indoor dust (870 μg/g) collected within 0.5 km of a plant exceeded levels previously found in suburban and urban areas, but did decrease outside 1.0 km to the upper end of background concentrations. Mn concentrations in attic dust were approximately 120 times larger than other indoor dust levels, consistent with historical emissions that yielded high airborne concentrations in the region. Considering the potential health effects that are associated with chronic manganese inhalation and ingestion exposure, remediation of soil near the plants and frequent, on-going hygiene indoors may decrease residential exposure and the likelihood of adverse health effects

MEK1/2 regulate normal BCR and ABL1 tumor-suppressor functions to dictate ATO response in TKI-resistant Ph+ leukemia

Resistance to tyrosine kinase inhibitors (TKIs) remains a clinical challenge in Ph-positive variants of chronic myeloid leukemia. We provide mechanistic insights into a previously undisclosed MEK1/2/BCR::ABL1/BCR/ABL1-driven signaling loop that may determine the efficacy of arsenic trioxide (ATO) in TKI-resistant leukemic patients. We find that activated MEK1/2 assemble into a pentameric complex with BCR::ABL1, BCR and ABL1 to induce phosphorylation of BCR and BCR::ABL1 at Tyr360 and Tyr177, and ABL1, at Thr735 and Tyr412 residues thus provoking loss of BCR's tumor-suppression functions, enhanced oncogenic activity of BCR::ABL1, cytoplasmic retention of ABL1 and consequently drug resistance. Coherently, pharmacological blockade of MEK1/2 induces dissociation of the pentameric MEK1/2/BCR::ABL1/BCR/ABL1 complex and causes a concurrent BCRY360/Y177, BCR::ABL1(Y360/Y177) and cytoplasmic ABL1(Y412/T735) dephosphorylation thereby provoking the rescue of the BCR's anti-oncogenic activities, nuclear accumulation of ABL1 with tumor-suppressive functions and consequently, growth inhibition of the leukemic cells and an ATO sensitization via BCR-MYC and ABL1-p73 signaling axes activation. Additionally, the allosteric activation of nuclear ABL1 was consistently found to enhance the anti-leukemic effects of the MEK1/2 inhibitor Mirdametinib, which when combined with ATO, significantly prolonged the survival of mice bearing BCR::ABL1-T315I-induced leukemia. These findings highlight the therapeutic potential of MEK1/2-inhibitors/ATO combination for the treatment of TKI-resistant leukemia

Altered expression of membrane-bound and soluble CD95/Fas contributes to the resistance of fibrotic lung fibroblasts to FasL induced apoptosis

BACKGROUND: An altered susceptibility of lung fibroblasts to Fas-induced apoptosis has been implicated in the pathogenesis of pulmonary fibrosis; however, the underlying mechanism is not completely understood. Here, we studied the susceptibility of lung fibroblasts, obtained from patients with (f-fibs) and without pulmonary fibrosis (n-fibs), to FasL- (CD95L/APO-1) induced apoptosis in relation to the expression and the amounts of membrane-bound and soluble Fas. We also analysed the effects of tumor necrosis factor-β on FasL-induced cell death. METHODS: Apoptosis was induced with recombinant human FasL, with and without prior stimulation of the fibroblasts with tumor necrosis factor-α and measured by a histone fragmentation assay and flow cytometry. The expression of Fas mRNA was determined by quantitative PCR. The expression of cell surface Fas was determined by flow cytometry, and that of soluble Fas (sFas) was determined by enzyme-linked immunosorbent assay. RESULTS: When compared to n-fibs, f-fibs were resistant to FasL-induced apoptosis, despite significantly higher levels of Fas mRNA. F-fibs showed lower expression of surface-bound Fas but higher levels of sFas. While TNF-α increased the susceptibility to FasL-induced apoptosis in n-fibs, it had no pro-apoptotic effect in f-fibs. CONCLUSIONS: The data suggest that lower expression of surface Fas, but higher levels of apoptosis-inhibiting sFas, contribute to the resistance of fibroblasts in lung fibrosis against apoptosis, to increased cellularity and also to increased formation and deposition of extracellular matrix

Preferred Spatial Frequencies for Human Face Processing Are Associated with Optimal Class Discrimination in the Machine

Psychophysical studies suggest that humans preferentially use a narrow band of low spatial frequencies for face recognition. Here we asked whether artificial face recognition systems have an improved recognition performance at the same spatial frequencies as humans. To this end, we estimated recognition performance over a large database of face images by computing three discriminability measures: Fisher Linear Discriminant Analysis, Non-Parametric Discriminant Analysis, and Mutual Information. In order to address frequency dependence, discriminabilities were measured as a function of (filtered) image size. All three measures revealed a maximum at the same image sizes, where the spatial frequency content corresponds to the psychophysical found frequencies. Our results therefore support the notion that the critical band of spatial frequencies for face recognition in humans and machines follows from inherent properties of face images, and that the use of these frequencies is associated with optimal face recognition performance

Benefit of an electronic head‐mounted low vision aid

Purpose: To evaluate the efficacy of electronic head-mounted low vision aid (e-LVA) SightPlus (GiveVision, UK, givevision.net) and to determine which people with low vision would see themselves likely using an e-LVA like this. Methods: Sixty participants with low vision aged 18 to 93 used SightPlus during an in-clinic study session based on a mixed methods design. Visual acuity (ETDRS), contrast sensitivity (Pelli-Robson) and reading performance (MNREAD) were measured binocularly at baseline (no device), with the device in ‘normal’ mode (zoom only), and with preferred enhanced mode (zoom and one of four digital image enhancements). At the end of the session, a short questionnaire recorded willingness to use an e-LVA like SightPlus, potential use cases, positive/negative comments and adverse effects. Results: Binocular distance visual acuity improved significantly by 0.63 logMAR on average (p < 0.0001) to 0.20 logMAR. Contrast sensitivity improved significantly by 0.22 log units (p < 0.0001) to 1.21 log units with zoom only and by 0.40 log units to 1.37 log units with zoom and preferred image enhancement. Reading performance improved significantly for near visual acuity and critical print size (p < 0.015), although reading speed significantly decreased (p < 0.0001). Nearly half (47%) of the participants indicated they would use an e-LVA like SightPlus, especially for television, reading and entertainment (e.g. theatre). Multivariate logistic regression showed that proportion of lifetime affected by sight loss, baseline contrast sensitivity and use of electronic LVAs explained 41% of the variation in willingness to use. Conclusions: SightPlus improves visual function in people with low vision and would be used in its current form by one half of the people who tried it. Adverse effects were infrequent and resolved when the device was removed. Future work should focus on comparing e-LVAs through repeatable real-world tasks and impact on quality of life