A novel water-injectivity model and experimental validation with CT-scanned corefloods

Injectivity decline is an issue during produced-water reinjection (PWRI) for water disposal in aquifers, waterflooding, chemical enhanced oil recovery, and geothermal-energy exploitation. A novel model for injectivity decline under flow conditions reminiscent of PWRI was developed taking into account deep-bed filtration and buildup of external filter cake. A distinct feature of the model is that it describes particle-retention kinetics responsible for internal filtration by an exponential decaying function of the retained-particle concentration. The corresponding nonlinear governing partial-differential equations were solved numerically and coupled with a known analytical model for external filtration with the concept of transition time. Coreflood experiments consisting of the injection of brine containing suspended hematite particles (volume fractions in the range of 2 to 6 ppm) were also performed. Computed-tomography (CT) scans of the core were taken to obtain deposition profiles along the core at different times. In addition, effect of various parameters (particle concentration and number of grids) on injectivity was investigated. From CT-scan and optical-microscope analyses, it was found that surface deposition in the porous medium and face plugging at the injection face of the core were responsible for decline in injectivity. The transition time from pure internal to external filtration was accurately determined from the CT-scan and pressure data. The newly proposed model and experiments were found to be in excellent agreement, indicating that the adopted retention function is a good heuristic description of particle retention.Ramesh Chandra Yerramilli, P. L. J. Zitha, Sanjay Surya Yerramilli, Pavel Bedrikovetsk

Cloud point and thermodynamic parameters of a non-ionic surfactant heptaoxyethylene dodecyl ether (C₁₂E₇) in presence of various organic and inorganic additives

1284-1290Cloud points (CPs) of heptaoxyethylene dodecyl ether (C12E7) in the presence of varying concentrations of additives such as inorganic salts, alkanols, diols, glycols and their ethers, hydroptopes and short chain tetraalkylammonium salts are measured and the increase/decrease in CP is discussed. While inorganic anions decrease the CP due to the “salting out” (dehydration) effect and follow the Hofmeister series, an increase in CP by CNS- and I- ions is governed by the “salting in” effect. Short chain alcohols (4), diols (6) and ethylene glycol ethers, diethylene glycol, propylene glycol, dipropylene glycol (4) increase the CP whereas a decrease is seen in the case of higher homologues. This increasing/decreasing effect of alcohols and diols and their monoalkyl ethers is ascribed to their function as a cosolvent/cosurfactant for C12E7 micellar systems. Both hydrotropes and short chain tetraalkylammonium salts increased CP of C12E7 to 100 °C at very low concentration. The thermodynamic parameters of these mixtures are also calculated at varying additive concentrations.<span style="mso-fareast-font-family: AdvGulliv-R;mso-bidi-font-family:AdvGulliv-R;letter-spacing:-.1pt;mso-ansi-language: EN-IN;mso-fareast-language:EN-IN" lang="EN-GB"> <span style="letter-spacing: -.1pt;mso-ansi-language:EN-IN" lang="EN-IN">As the solubility of non-ionic surfactant containing heptapolyoxyethylene hydrophilic chain is highest at the cloud point, the thermodynamic parameters are calculated at this temperature. The results show that the standard Gibbs free energy change (ΔG), the enthalpy (ΔH) and the entropy (ΔS) at the cloud point are positive or negative depending on the nature of the additives. </span

Plasma Symmetric Dimethylarginine Concentration in Dogs with Acute Kidney Injury and Chronic Kidney Disease.

BACKGROUND Symmetric dimethylarginine (SDMA) is considered a biomarker for early detection of renal dysfunction in human patients with acute kidney injury (AKI). At present, no studies exist analyzing the relevance of SDMA in dogs with AKI. HYPOTHESIS/OBJECTIVES SDMA would correctly identify dogs with renal disease but would not be able to differentiate between AKI and CKD. ANIMALS Eighteen healthy control dogs, 48 dogs with AKI, and 29 dogs with CKD. METHODS Prospective study. Dogs with kidney disease were categorized as having AKI or CKD according to the history, clinical signs, laboratory findings, and results of diagnostic imaging. Plasma SDMA concentration was measured by IDEXX Laboratories. SDMA/creatinine ratio was calculated in dogs with AKI or CKD. RESULTS Median SDMA concentrations were 8.5 μg/dL (6-12 μg/dL), 39.5 μg/dL (8->100 μg/dL), and 35 μg/dL (12->100 μg/dL), in healthy, AKI, and CKD, respectively. SDMA concentrations were significantly higher in dogs with AKI (P < .0001) or CKD (P < .0001) in comparison with healthy dogs. Median SDMA/creatinine ratio in dogs with AKI and CKD was 6.5 (1.7-20.9) and 10 (2.4-33.9) (P = .0004), respectively. Although there was overlap of the SDMA/creatinine ratio in dogs with AKI or CKD, it was significantly higher in dogs with CKD compared to dogs with AKI (P = .0004). CONCLUSIONS AND CLINICAL IMPORTANCE In this population, SDMA was suitable for identifying dogs affected by AKI or CKD, but could not differentiate between them

Healthcare worker access to molnupiravir: A case series.

Molnupiravir, an oral antiviral shown to reduce COVID-19 severity, is available in Australia via the Pharmaceutical Benefits Scheme (PBS) for treatment of mild-moderate COVID-19. For people less than 70 years of age it is only available with risk factors for severe disease, hence the majority of healthcare workers do not qualify. Currently, Australian health services are under considerable strain due to COVID-related staff shortages. Thirty staff members of a tertiary hospital, not eligible under the PBS, were offered molnupiravir within the first five days of COVID-19 illness. Their median age was 43 years, and 73% were female. All completed treatment with rates of adverse events that were low and comparable with clinical trial data. The reported duration of illness ranged from 1-16 days with a median of four days. A negative rapid antigen test on the final day of treatment was reported in 81% of people, and 73% reported being well enough to return to work at the completion of mandatory isolation. Only 22% of people reported transmission in their household after they commenced treatment. The implementation of a policy allowing access to molnupiravir outside of PBS recommendations for healthcare workers with mild-moderate COVID-19 may have important individual benefits to workers health and wellbeing and help alleviate the acute staff shortages experienced currently by the Australian healthcare workforce

A phase Ib trial of combined PKC and MEK inhibition with sotrastaurin and binimetinib in patients with metastatic uveal melanoma.

BACKGROUND: Uveal melanoma is a disease characterized by constitutive activation of the G alpha pathway and downstream signaling of protein kinase C (PKC) and the mitogen-activated protein kinase (MAPK) pathway. While limited clinical activity has been observed in patients with metastatic disease with inhibition of PKC or MEK alone, preclinical data has demonstrated synergistic antitumor effects with concurrent inhibition of PKC and MEK. METHOD: We conducted a phase Ib study of the PKC inhibitor sotrastaurin in combination with the MEK inhibitor binimetinib in patients with metastatic uveal melanoma using a Bayesian logistic regression model guided by the escalation with overdose control principle (NCT01801358). Serial blood samples and paired tumor samples were collected for pharmacokinetic (PK) and pharmacodynamic analysis. RESULTS: Thirty-eight patients were treated across six dose levels. Eleven patients experienced DLTs across the five highest dose levels tested, most commonly including vomiting (n=3), diarrhea (n=3), nausea (n=2), fatigue (n=2) and rash (n=2). Common treatment related adverse events included diarrhea (94.7%), nausea (78.9%), vomiting (71.1%), fatigue (52.6%), rash (39.5%), and elevated blood creating phosphokinase (36.8%). Two dose combinations satisfying criteria for the maximum tolerated dose (MTD) were identified: (1) sotrastaurin 300 mg and binimetinib 30 mg; and, (2) sotrastaurin 200 mg and binimetinib 45 mg. Exposure to both drugs in combination was consistent with single-agent data for either drug, indicating no PK interaction between sotrastaurin and binimetinib. Stable disease was observed in 60.5% of patients treated. No patient achieved a radiographic response per RECIST v1.1. CONCLUSIONS: Concurrent administration of sotrastaurin and binimetinib is feasible but associated with substantial gastrointestinal toxicity. Given the limited clinical activity achieved with this regimen, accrual to the phase II portion of the trial was not initiated

Phase I dose-escalation study of the protein kinase C (PKC) inhibitor AEB071 in patients with metastatic uveal melanoma

Experimentele farmacotherapi