Assessment strategies for mixing in very viscous gas-liquid two-phase flows

Bottom heating approach for glass melting offers potential benefits of higher efficiency and lower emissions compared to the conventional surface fired melters with burners above the bath surface. Recent advances in the enabling technologies such as burners, controls, heat recovery and refractive materials have led to successful demonstration of bottom heating Submerged Combustion Melting (SCM) of glass. In the reactor, combustion products of natural gas combustion are bubbled through the three phase recirculating tank reactor. The turbulence generated by the rising bubble column causes rapid heating and mixing of the charge resulting in fast melting and homogeneous composition of the product. Detailed understanding of such two-phase gas liquid flows is imperative for developing efficient multi-phase reactors through precise control of mixing and reaction kinetics. The bubble column, is a good apparatus for an elementary experimental study and numerical modeling of such flows. In this study, the hydrodynamics of the bubble column are investigated to develop strategies for assessment of mixing in the system. For the numerical part two approaches are used:;i) Using a commercial software ANSYS FLUENT with an Eulerian-Eulerian approach to model the bubble and the continuous phase and.;ii) Using an in house LES based Navier-Stokes solver with the Eulerian-Lagrangian method which uses the Particle-in-Ball approach for the Lagrangian particle tracking of the discrete phase (bubbles).;The efficacy of these methods in predicting the plume oscillation period (POP) over a wide range of superficial gas velocities is studied. An attempt is made to simulate the effect of viscosity on such flows. An unheated laboratory scale model with a very viscous primary phase is used for experiments, to better understand the effect of viscosity on the hydrodynamics of the bubbles rising and by extension the mixing obtained in the system

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

BACKGROUND Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. METHODS In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH, non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2-F3, or F1 with at least one accompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpoints for the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2-F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. FINDINGS Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1-F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2-F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1-F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). INTERPRETATION Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes. FUNDING Intercept Pharmaceuticals

Phosphatidate phosphatase : Activity and properties in fetal and adult rat lung

The purpose of this work is to compare the properties of phosphatidate phosphatase (-[alpha]-phosphatidate phosphohydrolase, EC 3.1.3.4) in fetal and adult rat lung and to establish the developmental profile of activity measured under optimal conditions. The maximal pH of 6.0-7.0 and the inhibition by fluoride, Ca2+ and detergents were similar for both adult and fetal. Phosphatidate phosphohydrolase activity was located in both mitochondria and microsomes. The localizations of marker enzymes indicated that the activity in these subfractions was not a result of cross contaminations. Very low activity was detected in the supernatant fraction and no Mg2+ requirement was demonstrable. The activity in the particulate fraction was about 50% of the adult from 18 day gestation until birth. Following birth, the activity rapidly increased to adult levels. Dipalmitoyl, dioleoyl and diacyl glycerol 3-phosphates are all utilized well as substrates. 1,2-dipalmitoyl-sn-glycerol 3-phosphate was hydrolyzed faster under maximal conditions. The velocity-substrate curves tended to be sigmoidal, particularly when 1,2-dipalmitoyl-sn-glycerol 3-phosphate was the substrate. Estimated apparent Km values of 0.02-0.03 mM were obtained for fetal and adult preparations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22525/1/0000069.pd

Fiber Bragg grating-based high temperature sensor and its low cost interrogation system with enhanced resolution

A fiber Brag grating-based high temperature sensor together with a low cost, high speed and compact size interrogation system using a long period grating was designed, developed and tested. The designed sensor measures the temperature from room temperature to 550 °C. The sensor head was configured by encapsulating an fiber Brag grating (type-I) of Bragg resonance wavelength at 1552.88 nm in a capillary tube made of copper. Long period grating with peak transmission loss at 1550 nm was employed to convert the wavelength information from fiber Brag grating into an intensity modulated signal. Temperature related optical intensity information was again converted into its equivalent electrical signal by using a photodiode. The achieved resolution of the sensor was found to be 0.5 °C

Proof-of-concept study to evaluate the safety and efficacy of saroglitazar in patients with primary biliary cholangitis

Saroglitazar is a novel peroxisome proliferator-activated receptor (PPAR) agonist with dual agonistic properties (α/γ). Due to a strong mechanistic rationale, we aimed to test the safety and efficacy of saroglitazar in patients with primary biliary cholangitis (PBC) who were either ursodeoxycholic acid (UDCA) resistant or intolerant. In this double-blind, phase II proof-of-concept trial, 37 patients with PBC were randomized to saroglitazar 4 mg (n = 13), saroglitazar 2 mg (n = 14), or placebo (n = 10) daily for 16 weeks. The primary efficacy endpoint was the reduction in alkaline phosphatase (ALP) level at Week 16. A significant reduction of mean ALP levels was observed at Week 16 relative to baseline in both the saroglitazar 4 mg (least-squares [LS] mean =-163.3 U/L, SE = 25.1, p <0.001) and 2 mg (LS mean =-155.8 U/L, SE = 24.4, p <0.001) groups, compared with placebo (LS mean =-21.1 U/L, SE = 28.9). Treatment with saroglitazar resulted in a rapid reduction of ALP concentration at Week 4 that was sustained through the study duration. At least 1 treatment-emergent adverse event occurred in 11 (84.6%) patients in the saroglitazar 4 mg group, in 12 (85.7%) patients in the 2 mg group and in 8 (80%) patients in the placebo group. Study drug was discontinued in 4 patients (3 patients in the 4 mg group and 1 patient in the 2 mg group) due to aminotransferase increases that promptly returned to baseline values after drug discontinuation. Saroglitazar at 2 mg and 4 mg daily was tolerated and resulted in rapid and sustained improvements in ALP. Further studies are underway at a daily dose of 2 mg and 1 mg due to the higher incidence of elevated liver enzymes observed with the 4 mg dose. NCT03112681 Saroglitazar resulted in a rapid and sustained improvement in alkaline phosphatase levels in patients with primary biliary cholangitis. The mean percentage reductions in alkaline phosphatase levels were 49% and 51% in the saroglitazar 4 mg and 2 mg groups compared to 3% in the placebo group. [Display omitted] •Saroglitazar is a novel peroxisome proliferator-activated receptor (PPAR) agonist with dual agonistic properties (α/γ).•A statistically significant reduction in ALP levels was observed at Week 16 in saroglitazar 4 mg and 2 mg groups compared to placebo.•The reduction in ALP levels corresponded to a mean % reduction of 49% and 51% in the saroglitazar 4 mg and 2 mg groups, respectively