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Understanding and predicting the propagation, deposition and resuspension of suspended particulate matter (SPM) in river networks is important for managing water resources, ecological habitat, pollution, navigation, hydropower generation, reservoir sedimentation, etc. Observational data are scarce and costly, and there is little feedback on the efficiency of numerical simulation tools for compensating the lack of data on a river scale of several hundreds of kilometers. This paper aims at exploring the use of a one-dimensional (1-D) hydrodynamical model for understanding the source and fate of SPM during complex events...

Three proteasome inhibitors have garnered regulatory approvals in various multiple myeloma settings but drug resistance is an emerging challenge, and this has prompted interest in blocking upstream components of the ubiquitin-proteasome pathway. One such attractive target is the E1 ubiquitin activating enzyme (UAE), and we therefore evaluated the activity of TAK-243, a novel and specific UAE inhibitor. TAK-243 potently suppressed myeloma cell line growth, induced apoptosis, and activated caspases while decreasing the abundance of ubiquitin-protein conjugates...

BACKGROUND: Treatment programs for people who inject drugs (PWID), including prisoners, are important for achieving hepatitis C elimination targets. There are multiple barriers to treatment of hepatitis C in prisons, including access to specialist physicians, testing and antiviral therapy, short prison sentences, and frequent inter-prison transfer. A state-wide program for assessment and management of hepatitis C was developed in Victoria, Australia to improve access to care for prisoners...

Long term and high resolution data on water discharge, suspended particulate matter (SPM) and contaminant concentrations in rivers are required for a better understanding of particulate transfers from the continental areas to the seas. The aim of this study was to provide a novel estimation of annual fluxes of SPM and related pollutants in the Rhône River from Lake Geneva to the Mediterranean Sea by combining high frequency or time-integrative monitoring and novel relations between SPM concentration (Cs) and water discharge (Q)...

A multi-technique approach is proposed to study sand dynamics in an engineered piedmont river. Only a few studies focused on such systems and innovative methodological protocols still need to be designed to better understand sand transport in piedmont rivers where bedload dynamics has been largely modified with nowadays a residual sand transport on a fixed gravel matrix. The proposed methodology is based on an analysis of bathymetry and turbidity measurements and on modelling, including the development of sediment rating curves and 2D numerical modelling, and using sediment budgeting for cross-validation...

The concept of the epithelial-to-mesenchymal transition (EMT) in epithelial cells has accelerated our understanding about cancer spreading. Fortunately, much of this information has been able to be extrapolated to non-epithelial cancers, such as glioblastoma (GBM). Interestingly, reactive astrocytes, which are present in the tumor edge in association with glioma cells, might also undergo EMT-like under stimuli of GBM cells. As result, the positive feedback of reactive astrocytes and glioma cells, could act to promote cancer progression making use of the dynamism of the mesenchymal phenotype...

BACKGROUND: Contact dermatitis affects up to 20% of the population. Patch testing for contact allergy may be needed to confirm the diagnosis. OBJECTIVES: To describe and discuss the results of patch tests performed in a city in southern Brazil. METHODS: A cross-sectional analysis was performed on all skin test results over ten years. Variables such as gender, age at the time of testing, and test results were evaluated. Triggering factors, duration of complain, and previous medications used related to the clinical history were retrieved for some patients by reviewing their medical records...

Tic disorders are characterized by a class of responses assumed to be neurobiological in origin. Still, several studies have shown that tic frequency can be influenced by antecedent environmental events and social consequences. Prior reviews have summarized the effects of environmental events but have not examined relations between tic diagnosis, behavioral deficits (e.g., intellectual disability), tic topography, and the consequences observed to maintain tics. These variables might be important when attempting to predict or identify relevant consequences...

Purpose: Waldenström's macroglobulinemia is an incurable lymphoproliferative disorder driven by an L265P mutation in the myeloid differentiation primary response gene 88 ( MYD88 ), which activates downstream NF-κB signaling through the Myddosome. As this pathway depends in part on activity of interleukin-1 receptor-associated kinases (IRAKs)-1 and -4, we sought to evaluate the potential of the IRAK1/4 inhibitor R191 in preclinical models. Experimental Design: Patient-derived cell lines and primary samples were used in both in vitro and in vivo experiments to model Waldenström's macroglobulinemia and its response to IRAK1/4 inhibitors...

Glioblastoma is the worst and most common primary brain tumor. Here, we demonstrated the role of CD73, an enzyme responsible for adenosine (ADO) production, in glioblastoma progression. ADO increased glioma cell viability via A1 receptor sensitization. CD73 downregulation decreased glioma cell migration and invasion by reducing metalloproteinase-2 and vimentin expression and reduced cell proliferation by 40%, which was related to necrosis and sub-G1 phase blockage of cell cycle. Those effects also involved the stimulation of Akt/NF-kB pathways...

INTRODUCTION: An outbreak of Lassa Fever (LF) reported and confirmed in Ondo state, Southwest Nigeria in January 2016 was investigated. This paper provides the epidemiology of the LF and lessons learnt from the investigation of the outbreak. METHODS: The incidence management system (IMS) model was used for the outbreak coordination. Cases and deaths were identified through the routine surveillance system using standard definitions for suspected and confirmed cases and deaths respectively...

BACKGROUND: Prostate cancer is the leading type of cancer among men in more developed countries. Incidence trends and survival rates could differ by age groups considering potential differences in the frequency of PSA testing, types of cancers and medical management. Our objective was to compare incidence trends and survival rates of prostate cancer between men aged ≥75 and 60-74 years. METHOD: We analyzed data from a population-based cancer registry in Isère, France...

BACKGROUND: To achieve the World Health Organization hepatitis C virus (HCV) elimination targets, it is essential to increase access to treatment. Direct-acting antiviral (DAA) treatment can be provided in primary healthcare services (PHCS), improving accessibility, and, potentially, retention in care. Here, we describe our protocol for assessing the effectiveness of providing DAAs in PHCS, and the impact on the HCV care cascade. In addition, we reflect on the challenges of conducting a model of care study during a period of unprecedented change in HCV care and treatment...

Modern marine turtles (chelonioids) are the remnants of an ancient radiation that roots in the Cretaceous. The oldest members of that radiation are first recorded from the Early Cretaceous and a series of species are known from the Albian-Cenomanian interval, many of which have been allocated to the widespread but poorly defined genus Rhinochelys , possibly concealing the diversity and the evolution of early marine turtles. In order to better understand the radiation of chelonioids, we redescribe the holotype and assess the taxonomy of Rhinochelys amaberti Moret (1935) (UJF-ID...

Bromodomain and extraterminal (BET) domain containing protein (BRD)-4 modulates the expression of oncogenes such as c-myc, and is a promising therapeutic target in diverse cancer types. We performed pre-clinical studies in myeloma models with bi-functional protein-targeting chimeric molecules (PROTACs) which target BRD4 and other BET family members for ubiquitination and proteasomal degradation. PROTACs potently reduced the viability of myeloma cell lines in a time-dependent and concentration-dependent manner associated with G0 /G1 arrest, reduced levels of CDKs 4 and 6, increased p21 levels, and induction of apoptosis...

Predictions made under low response requirements inherent in most preference assessments (PAs) do not guarantee the utility of stimuli in treatments. We examined whether PA rank would predict how well stimuli supported compliance for children with escape-maintained problem behavior by examining the relation between PA rank and demand elasticity across five fixed-ratio values. Three patterns were observed: All stimuli were selected equally across values, higher ranked stimuli were selected more at higher values, and something other than the highest ranked stimulus was selected more at higher values (i...

Behavioral momentum theory is a quantitative framework used to characterize the persistence of behavior during response disruptors as a function of baseline stimulus-reinforcer relations. Results of several investigations have shown that alternative reinforcement can increase the resistance to change of a target response during extinction. In the present study, concomitant variable-interval fixed-time schedules of reinforcement for problem behavior were employed to simulate naturalistic situations involving the superimposition of response-independent reinforcers on a baseline schedule of reinforcement for problem behavior, as in the common use of noncontingent reinforcement treatments...

Transitions from one activity to another may evoke problem behavior from individuals with intellectual disabilities. One explanation for the occurrence of problem behavior could be the change in relative densities of reinforcement between the two activities. We conducted a descriptive assessment of problem behavior with four children during transitions to and from several different contexts. We observed that, in most cases, the probability of problem behavior was greater during a transition to an activity with a lower density of reinforcement than during a transition to an activity with a higher density of reinforcement...

INTRODUCTION: Dominant heterozygous familial hypercholesterolemia (FH) is frequent (prevalence, 1/500 to 1/250) and leads to severe and premature cardiovascular complications. It is easily detected, and its treatment is effective. However, recommendations for screening are not followed worldwide. OBJECTIVES: The aim of this study was to evaluate the knowledge and practices of doctors in the Isère department, France, regarding screening and treatment of FH in children...

Immuno-oncology approaches mainly utilize monoclonal antibodies or protein-based scaffolds that bind with high affinity to cancer cells and can generate an immune response. Peptides can also bind with high affinity to cancer cells and are intermediate in size between antibodies and small molecules. They are also synthetically accessible and therefore easily modified to optimize their stability, binding affinity and selectivity. Here we describe the design of immune system engagers (ISErs), a novel class of synthetic peptide-based compounds that bind specifically to cancer cells and stimulate the immune system...