Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release solid oral dosage forms containing mefloquine hydrochloride as ...the only active pharmaceutical ingredient (API) are reviewed. The solubility and permeability data of mefloquine hydrochloride as well as its therapeutic use and therapeutic index, its pharmacokinetic properties, data related to the possibility of excipient interactions and reported BE/bioavailability studies were taken into consideration. Mefloquine hydrochloride is not a highly soluble API. Since no data on permeability are available, it cannot be classified according to the Biopharmaceutics Classification System with certainty. Additionally, several studies in the literature failed to demonstrate BE of existing products. For these reasons, the biowaiver cannot be justified for the approval of new multisource drug products containing mefloquine hydrochloride. However, scale-up and postapproval changes (HHS-FDA SUPAC) levels 1 and 2 and most EU type I variations may be approvable without in vivo BE, using the dissolution tests described in these regulatory documents.
The aim of this study was to provide an overview of the literature available on dynamic contrast-enhanced computed tomography (DCE-CT) as a tool to evaluate treatment response in patients with lung ...cancer. This systematic review was compiled according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only original research articles concerning treatment response in patients with lung cancer assessed with DCE-CT were included. To assess the validity of each study we implemented Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). The initial search yielded 651 publications, and 16 articles were included in this study. The articles were divided into groups of treatment. In studies where patients were treated with systemic chemotherapy with or without anti-angiogenic drugs, four out of the seven studies found a significant decrease in permeability after treatment. Four out of five studies that measured blood flow post anti-angiogenic treatments found that blood flow was significantly decreased. DCE-CT may be a useful tool in assessing treatment response in patients with lung cancer. It seems that particularly permeability and blood flow are important perfusion values for predicting treatment outcome. However, the heterogeneity in scan protocols, scan parameters, and time between scans makes it difficult to compare the included studies.
In recent times Euglena gracilis Z was employed as primary producer in closed environmental life-support system (CELSS), e.g. in space research. The photosynthetic unicellular flagellate is not ...capable of utilizing nitrate, nitrite, and urea as nitrogen source. Therefore, ammonium is supplied as an N-source in the lab (provided as diammonium-dihydrogenphosphate, (NH4)2HPO4) to E. gracilis cultures. While nitrate exerts low toxicity to organisms, ammonium is harmful for many aquatic organisms especially, at high pH-values, which causes the ionic NH4+ (low toxicity) to be partially transformed into the highly toxic ammonia, NH3. In earlier reports, Euglena gracilis was described to grow with various amino acids as sole N-source. Our aim was to investigate alternatives for (NH4)2HPO4 as N-source with lower toxicity for organisms co-cultivated with Euglena in a CELSS. The growth kinetics of Euglena gracilis cultures was determined in the presence of different amino acids (glycine, glutamine, glutamic acid, leucine, and threonine). In addition, uptake of those amino acids by the cells was measured. Cell growth in the presence of glycine and glutamine was quite comparable to the growth in (NH4)2HPO4 containing cultures while a delay in growth was observed in the presence of leucine and threonine. Unlike, aforementioned amino acids glutamate consumption was very poor. Cell density and glutamate concentration were almost unaltered throughout the experiment and the culture reached the stationary phase within 8 days. The data are compared with earlier studies in which utilization of amino acids in Euglena gracilis was investigated. All tested amino acids (glutamate with limitations) were found to have the potential of being an alternative N-source for Euglena gracilis. Hence, these amino acids can be used as a non-toxic surrogate for (NH4)2HPO4.
Pion photoproduction in the \\gamma p \rightarrow \pi ^0 p\ reaction has been measured in the FROST experiment at the Thomas Jefferson National Accelerator Facility. In this experiment, circularly ...polarized photons with energies up to 3.082 GeV impinged on a transversely polarized frozen-spin target. Final-state protons were detected in the CEBAF Large Acceptance Spectrometer. Preliminary results of the polarization observables T and F have been extracted. The data generally agree with predictions of present partial-wave analyses, but also show marked differences. The data will constrain further partial wave analyses and improve the extraction of proton resonance properties.
This study reports nutrient dynamics during the “Run-in-”, “Batch-” and “Staggered 1 - 3” production phases of African catfish (Clarias gariepinus Burchell, 1822) in commercial warm water ...recirculation aquaculture systems (RAS) under three different stocking densities, extensive (max 50 kg m−3; 35 fish tank−1), semi-intensive (max 100 kg m−3; 70 fish tank−1) and intensive (max 200 kg m−3; 140 fish tank−1) at similar system volumes of 13.9, 15.1 and 16.9 m3. The concentrations of the dissolved macronutrients Total Ammonia Nitrogen (TAN, as NH4+-N), nitrite (NO2−-N), nitrate (NO3−-N), Total Dissolved Nitrogen (TDN), Total Oxidized Nitrogen (TON), phosphorus (measured as ortho-phosphate) (P), potassium (K), calcium (Ca) and magnesium (Mg) were monitored with colorimetric analyses and budgeted for potential use for aquaponics. We found, that stocking density and RAS maintenance affected oxygen thresholds, subsequently affecting nutrient concentrations of NO3−-N due to denitrification. K proportionally increased with feed input, while Ca, Mg and P reacted disproportionally, because of precipitation. Highest deviation was observed for TON, especially when oxygen levels dropped <6 mg L−1. Maintenance intervals, feed ratios and resulting oxygen levels changed dissolved nutrient concentrations, with highest concentrations under intensive stocking density, medium feed input and oxygen > 6 mg L−1, and lowest under semi-intensive stocking density, high feed input and oxygen > 6 mg L−1. Calculated nutrient budgets under consideration of stocking density, feed input and water exchange rates demonstrated that the production conditions affected nutrient availability and output. The macronutrient ratios TDN, P, K, Ca and Mg as well as the physical and chemical parameters changed constantly under production conditions, due to daily adjusted feeding and RAS maintenance. This must be considered during process management, in stand-alone commercial catfish aquaculture as well as in integrated systems such as aquaponics.
•Nutrient dynamics in C. gariepinus RAS under commercial production conditions are not assessed.•To design and operate aquaponics with C. gariepinus, knowledge on the system management on nutrient dynamics is required.•Management of C. gariepinus RAS affects nutrient dynamics unpredictably, necessitating tolerant plant species in aquaponics.•Investors and operators can use the results here for planning of aquaculture/aquaponic facilities and management plans
We have measured the differential cross section for the gamman-->pi(-)p and gammap-->pi(+)n reactions at theta(c.m.)=90 degrees in the photon energy range from 1.1 to 5.5 GeV at Jefferson Lab (JLab). ...The data at E(gamma) greater, similar 3.3 GeV exhibit a global scaling behavior for both pi(-) and pi(+) photoproduction, consistent with the constituent counting rule and the existing pi(+) photoproduction data. Possible oscillations around the scaling value are suggested by these new data. The data show enhancement in the scaled cross section at a center-of-mass energy near 2.2 GeV. The cross section ratio of exclusive pi(-) to pi(+) photoproduction at high energy is consistent with the prediction based on one-hard-gluon-exchange diagrams.
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