Improper Formulation Research Articles

Comparative Efficiency of Polyethylene Glycol, Ammonium Sulphate, Methanol Precipitation, and Ultrafiltration Techniques for the Down Streaming of Viral Antigen

Background: Foot and mouth disease (FMD) is ubiquitous worldwide but endemic in many countries of Africa, Asia, South America, and the Middle East. Many reasons contribute to the incidence of viral diseases even in vaccinated animals. These reasons include low antigenic payload, low PD50, improper formulation, unstable vaccine containing antigen, and genetically different from field strain. Among these, the most important one is the low antigenic load per dose of the vaccine. Vaccine failure is mainly due to the direct use of virus suspension in the vaccine without the concentration of viral antigen. Another reason to concentrate the antigen is small volume storage in the vaccine bank. These issues are mostly concerned with developing countries like Pakistan which lack antigen concentration technology. The concentration of the virus is a major milestone to be achieved for the production of an effective vaccine as well as for the diagnostic tool.Methods: Different techniques including precipitation with polyethylene glycol, ammonium sulfate, methanol, and filtration through an ultra-filter membrane were used for the concentration of viral suspension. Antigen quantification in terms of µg/ml was determined through size exclusion chromatography by using Sephacryl S-300 as a stationary phase.Results: Percentage recovery of FMDV calculated through analysis of chromatograms found 77.80%, 59.75%, 32.50%, and 13.83% for polyethylene glycol, ammonium sulfate, ultra-filtration, and methanol treated samples respectively.Conclusion: Classical polyethylene glycol precipitation showed a maximum percentage recovery of foot and mouth disease virus as compared to other concentration methods.Keywords: Foot and mouth disease virus (FMDV); Concentration Methods; Polyethylene Glycol (PEG); Size Exclusion Chromatography (SEC); Sephacryl S-300

Regional challenges concerning derivation of suspended particulate matter concentration and water turbidity from water reflectance. A case study in the western Black Sea

Assessment of water quality indicators, such as Suspended Particulate Matter (SPM) concentration and water turbidity (TUR) is essential for marine ecosystems health evaluations. This work focuses on the estimation of these two variables from water-leaving reflectance measurements, either derived from in-situ observations or satellite data, for the western Black Sea basin. The regional characteristics of the water optically active constituents can have important impact on the quality of such estimations if not properly accounted for. We test several existing inversion algorithms and quantify their accuracy. New, regionally adapted methods are then proposed, together with a new formulation for a multi-conditional switching mechanism. Calibration of these models is performed based on SPM and TUR in-situ measurements. It is shown that the improvements achieved through regional adaptation can be significant. Application of these algorithms to Sentinel-3 OLCI satellite data reveals the consistency of the proposed methodology. Also, it shows the degree of uncertainty if improper formulations are used, with major impact on the absolute values of retrieved SPM or TUR.

Drug Traceability in Supply Chain of Healthcare using Blockchain-Based Approach

The supplychain for healthcare is an intricate web of inter connected businesses that includes manufacturers, distributors, pharmacies, hospitals, patients, and suppliersofrawmaterials.Duetoanumberofissues,suchascentralisedcontrol,conflictingstakeholder conduct, and a lack of information, tracking supply across this network is difficult. In additiontocreatinginefficiencieslikethosebroughttolightbytheCOVID-19pandemic[1], this complexity can make it more difficult to mitigate the problem of counterfeit pharmaceuticalsbecausetheycanquicklyinfiltratethehealthcaresupplychain.Drugsthat are intentionally manufactured fraudulently and/or mislabeled with regard to identity and/or source in order to pass for authentic goods are known as counterfeit drugs[2][3]. These prescriptions may include those with no active pharmaceutical ingredient (API), the wrong dosage, the wrong kind of API, a pollutants, or repackaged goods that have expired. It is possible forcertainfake drugs to be manufactured under unsatisfactory circumstances and with improper formulations[4].

Echinomycin: A Journey of Challenges

Echinomycin is a natural compound discovered and isolated from bacteria, introduced as a promising antibiotic and anticancer therapy. However, it failed clinically due to improper formulations and a short half-life. After the unsuccessful clinical trials, echinomycin was overlooked. Recently, a new mechanism of action has given some hope for reviving echinomycin as an inhibitor of hypoxia-inducible factor (HIF-1). In 2015, echinomycin received orphan drug designation for treating acute myeloid leukemia in the USA. Furthermore, advancements in drug delivery systems have provided new prospects to overcome the echinomycin formulation issues and explore further therapeutic benefits. This review details the echinomycin journey along with the main challenges of this potent drug and provides insights into possible future clinical applications.

Strategic Planning in Increasing Quality of Education

This research is motivated by the low quality of education in Indonesia, especially primary education. Improving the quality of education is a must to meet the needs of schools and communities. One of the efforts made to make schools an active forum in improving the quality of education is strategic planning. This study aims to explore school strategic planning, analyze, and plan strategic planning in improving the quality of education at SDN Jetis Bantul. Researchers used descriptive research with a qualitative approach. Data collection techniques in this study were in-depth interviews, participant observation and documentation. This study's subjects were the principal, members of the principal's work deliberation, supervisors, teachers, and the school committee. Data analysis techniques used are data, data reduction, data presentation, drawing conclusions and levers. The results show that: (1) strategic planning is carried out by making an annual work plan following the vision, mission and goals of the school formulated at the beginning of the school year, forming a school development team, implementing school planning by educational procedures, developing development and coaching results achieving goals. (2) implementing school management strategies to diagnose systematically, plan, design and compile documents, establish policies, motivate educators and education personnel, allocate human resources, and develop a supportive strategic culture. (3) The evaluation of the school management strategy is carried out by analyzing its suitability with the strategic plan; the evaluation results used to assess a program, improvements, or colours. Supporting strategic planning factors are excellent support from students, teachers, supervisors, committees, student guardians and the school environment. The obstacle encountered in school strategic planning is the problem of the improper formulation. The school collaborates with the school committee and student guardians to solve these inhibiting factors to overcome this.

Comparative Advantage of Using Bio-pesticides in Indian Agro-ecosystems

The use of unsustainable levels of plant protection chemicals and fertilizershas resulted in a steady decline in soil quality and crop productivity the world over. To combat this decline, agricultural practices must evolve to meet the growing global demand for food without irreversibly damaging the world’s natural resources.Biopesticides have tremendous potential to bring sustainability to agriculture and environmental safety.This article is part of a larger study conducted in India by the authors at theUniversité de Montréal with the support of Mitacs and Earth Alive Clean Technologies. In this research, farmers, manufacturers or suppliers of biopesticides, and R&D scientistswere interviewed, and their responses demonstratethe advantages of applyingmicrobial biopesticidesto field crops. Participants reported a15-30% increase in yields and crop production after the application ofbiopesticides, with better quality and quantity of fruits, grains, and tubers with a longer shelf life. Moreover, while the risk of croploss is high (60-70%) with chemicallygrown crops, this risk is reduced to 33% on average when crops are grown using biopesticides. The risk of crop loss is thus considerably reducedby the use ofbiopesticides.Yet, despite their positive impact on the health of humans, soil,ecosystems, andfriendly invertebrates,biopesticides face significant challenges and competition vis-à-vis synthetic pesticides for a variety of reasons. The development of biopesticides must overcome the problems of improper formulations, short shelf life, delayed action, and high market costs, as well as a variety oflegal/registration issues.

PC-2 A liposomal formulation of HIF-1α inhibitor echinomycin inhibits growth and metastasis of experimental model of breast cancer

PC-2 A liposomal formulation of HIF-1α inhibitor echinomycin inhibits growth and metastasis of experimental model of breast cancer

Revisiting bending theories of elastic gradient beams

In this paper, we discuss a problem of Bernoulli–Euler beam models development in the frame of the strain gradient and distortion gradient elasticity theories. Contradiction between some known size-dependent gradient beam models and analytical and numerical three-dimensional solutions found for the beam bending problems is shown. In particular, it is shown that in semi-inverse analytical solutions for a beam pure bending problem, the inverse squared dependence of normalized bending stiffness on the beam thickness could arise only due to wrong definition of the resultant bending moment and improper formulation of the boundary conditions on the top and bottom surfaces of the beam. In the correct semi-inverse solutions, finite values of normalized bending stiffness for ultra-thin gradient beams arise. The obtained results are also confirmed on the basis of 3D FE simulations realized for a pure and cantilever beam bending problems in the frame of simplified strain gradient elasticity theory. As a result, it is shown that the only correct approach for Bernoulli–Euler beam models development in gradient theories should ensures the fulfillment of boundary conditions on the top and bottom surfaces of the beam and corresponds to a model that assumed a uniaxial stress state of the beam. The consistent variational algorithm for the correct gradient beam models derivation is proposed.

The forensic medical aspects of the inappropriate medical care in the modern-day Ukraine

Despite the fact that the ever growing relevance of the problem of the inappropriate medical care was long ago brought to the worldwide attention, it has not been practically addressed in the Ukraine since the country gained independence in 1991. The objective of the present study was to consider the specific features of expert examination of the cases of inappropriate medical care as exemplified by the materials of the legal actions and lawsuits instituted against healthcare specialists violating their occupational duties. The results of forensic medical examination by the local Bureaux of forensic medical expertise concerning the 350 so-called malpractice suits instituted in the Ternopol, Zhitomir, and Chernovtsy regions during the period from 207 to 2016 were available for the analysis. The facts of inadequate and inappropriate medical care were documented in 245 (72.0%) cases. The frequency of diagnostic and therapeutic errors amounted to 29.7% and 26.9% respectively while the improper formulation of the medical documentation was recorded in 21.3% of the cases. The cases of poor organization of the diagnostic and treatment process accounted for 14.6% of the total whereas the improper behaviour of the medical personnel was reported in 7.5% of all the known cases of provision of the healthcare services. It is concluded that in the majority of the cases, the citizens of the modern-day Ukraine receive the inappropriate (insufficient and untimely) medical care. Over 80% of the cases of the inappropriate medical care currently provided in the country can be accounted for by the objective reasons, with each fifths case being due to the violation of professional responsibilities by the healthcare providers.

An Analytical Solution for Three-Component, Two-Phase Surfactant Flooding Dependent on the Hydrophilic/Lipophilic-Difference Equation and the Net-Average-Curvature Equation of State

SummaryMicroemulsion phase behavior is crucial to surfactant flooding performance and design. In previous studies, analytical/numerical solutions for surfactant flooding were developed dependent on the classical theory of multicomponent/multiphase displacement and empirical microemulsion phase-behavior models. These phase-behavior models were derived from empirical correlations for component-partition coefficients or from the Hand-rule model (Hand 1930), which empirically represents the ternary-phase diagram. These models may lack accuracy or predictive abilities, which may lead to improper formulation design or unreliable recovery predictions.To provide a more-insightful understanding of the mechanisms of surfactant flooding, we introduced a novel microemulsion phase-behavior equation of state (EOS) dependent on the hydrophilic/lipophilic-difference (HLD) equation and the net-average curvature (NAC) model, which is called HLD-NAC EOS hereafter. An analytical model for surfactant flooding was developed dependent on coherence theory and this novel HLD-NAC EOS for two-phase three-component displacement. Composition routes, component profile along the core, and oil recovery can be determined from the analytical solution.The analytical solution was validated against numerical simulation as well as experimental study. This HLD-NAC EOS based analytical solution enables a systematic study of the effects of phase-behavior-dependent variables on surfactant-flooding performance. The effects of solution gas and pressure on microemulsion phase behavior were investigated. It was found that an increase of solution gas and pressure would lead to enlarged microemulsion bank and narrowed oil bank. For a surfactant formulation designed at standard conditions, the analytical solution was able to quantitatively predict its performance under reservoir conditions.

Applications of multivariate modeling to neuroimaging group analysis: A comprehensive alternative to univariate general linear model

All neuroimaging packages can handle group analysis with t-tests or general linear modeling (GLM). However, they are quite hamstrung when there are multiple within-subject factors or when quantitative covariates are involved in the presence of a within-subject factor. In addition, sphericity is typically assumed for the variance–covariance structure when there are more than two levels in a within-subject factor. To overcome such limitations in the traditional AN(C)OVA and GLM, we adopt a multivariate modeling (MVM) approach to analyzing neuroimaging data at the group level with the following advantages: a) there is no limit on the number of factors as long as sample sizes are deemed appropriate; b) quantitative covariates can be analyzed together with within-subject factors; c) when a within-subject factor is involved, three testing methodologies are provided: traditional univariate testing (UVT) with sphericity assumption (UVT-UC) and with correction when the assumption is violated (UVT-SC), and within-subject multivariate testing (MVT-WS); d) to correct for sphericity violation at the voxel level, we propose a hybrid testing (HT) approach that achieves equal or higher power via combining traditional sphericity correction methods (Greenhouse–Geisser and Huynh–Feldt) with MVT-WS.To validate the MVM methodology, we performed simulations to assess the controllability for false positives and power achievement. A real FMRI dataset was analyzed to demonstrate the capability of the MVM approach. The methodology has been implemented into an open source program 3dMVM in AFNI, and all the statistical tests can be performed through symbolic coding with variable names instead of the tedious process of dummy coding. Our data indicates that the severity of sphericity violation varies substantially across brain regions. The differences among various modeling methodologies were addressed through direct comparisons between the MVM approach and some of the GLM implementations in the field, and the following two issues were raised: a) the improper formulation of test statistics in some univariate GLM implementations when a within-subject factor is involved in a data structure with two or more factors, and b) the unjustified presumption of uniform sphericity violation and the practice of estimating the variance–covariance structure through pooling across brain regions.

Comment: A potential bias in the databases of phytoplankton growth and microzooplankton grazing rates because of the improper formulation of the null hypothesis in dilution experiments

Comment.

Accessibilità e sicurezza dei farmaci in pediatria

[Accessibilty and safety of drugs in pediatrics] Many of pediatric drugs have not been tested and evaluate in children. The risks associated with the off-label use of drugs without pediatric indications include adverse effects, inefficacy, and improper formulation. Furthermore the use of magistral or officinal formulations to treat the pediatric population may be of poor quality. The objectives of EU Regulation 1901/2006 on medicinal products for pediatric are to improve the health of children by facilitating the development and availability of medicines for children, ensuring that medicines for use in children are of high quality, ethically researched and authorised appropriately, and improving the availability of information on the use of medicines for children. Peyona (caffeine citrate) is authorised for the treatment of primary apnea of premature newborns and it’s a good example of drug tested and evaluate in children.

Flux Evaluation in Primal and Dual Boundary-Coupled Problems

A crucial aspect in boundary-coupled problems, such as fluid-structure interaction, pertains to the evaluation of fluxes. In boundary-coupled problems, the flux evaluation appears implicitly in the formulation and consequently, improper flux evaluation can lead to instability. Finite-element approximations of primal and dual problems corresponding to improper formulations can therefore be nonconvergent or display suboptimal convergence rates. In this paper, we consider the main aspects of flux evaluation in finite-element approximations of boundary-coupled problems. Based on a model problem, we consider various formulations and illustrate the implications for corresponding primal and dual problems. In addition, we discuss the extension to free-boundary problems, fluid-structure interaction, and electro-osmosis applications.

If Vitamins Could Kill: Massive Hemolysis Following Naturopathic Vitamin Infusion

Hemolysis from naturopathic remedies remains poorly reported in the medical literature, although it is most commonly noted in the patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency. We report a case of massive intravascular hemolysis following the infusion of a naturopathic preparation that contains vitamins. A 47-year-old African-American man presented to the hospital with 3 days of fever, dyspnea, emesis, dark urine, and progressive confusion. His symptoms began 1 day following an infusion of a vitamin complex. His physical examination was significant for lethargy and scleral icterus. Initial laboratory studies were notable for anemia (hemoglobin, 3.3 g/dL and hematocrit, 11%), brisk reticulocytosis (33%), acute renal insufficiency (creatinine, 2.8 mg/dL), and indirect hyperbilirubinemia (total bilirubin, 4.4 mg/dL). His peripheral smear demonstrated "blister cells," erythrocytes that have been left devoid of precipitated hemoglobin by the spleen, which are commonly seen in patients with G6PD deficiency. His physician revealed that the infusion contained vitamins B and D complex, free amino acids, magnesium, and taurine. The patient clinically improved and was discharged to home. G6PD concentration was significantly reduced to 4.7 U/g Hb upon recovery. Life-threatening intravascular hemolysis may occur following a naturopathic vitamin infusion and may identify previously unknown G6PD deficiency. Since most properly formulated naturopathic treatments have few toxic ingredients, the possibilities of improper formulation, toxic diluents, or contaminants should be considered. Inadequate regulatory oversight of naturopathic remedies has the potential to allow serious toxicity especially in genetically predisposed individuals.

Nutritional aspects of food extrusion: a review

SummaryExtrusion cooking, as a multi‐step, multi‐functional and thermal/mechanical process, has permitted a large number of food applications. Effects of extrusion cooking on nutritional quality are ambiguous. Beneficial effects include destruction of antinutritional factors, gelatinisation of starch, increased soluble dietary fibre and reduction of lipid oxidation. On the other hand, Maillard reactions between protein and sugars reduce the nutritional value of the protein, depending on the raw material types, their composition and process conditions. Heat‐labile vitamins may be lost to varying extents. Changes in proteins and amino acid profile, carbohydrates, dietary fibre, vitamins, mineral content and some non‐nutrient healthful components of food may be either beneficial or deleterious. The present paper reviews the mechanisms underlying these changes, as well as the influence of process variables and feed characteristics. Mild extrusion conditions (high moisture content, low residence time, low temperature) improve the nutritional quality, while high extrusion temperatures (200 °C), low moisture contents (<15%) and/or improper formulation (e.g. presence of high‐reactive sugars) can impair nutritional quality adversely. To obtain a nutritionally balanced extruded product, careful control of process parameters is essential.

The ellipsoidal correction to the Stokes kernel for precise geoid determination

Solving the geodetic boundary-value problem (GBVP) for the precise determination of the geoid requires proper use of the fundamental equation of physical geodesy as the boundary condition given on the geoid. The Stokes formula and kernel are the result of spherical approximation of this fundamental equation, which is a violation of the proper relation between the observed quantity (gravity anomaly) and the sought function (geoid). The violation is interpreted here as the improper formulation of the boundary condition, which implies the spherical Stokes kernel to be in error compared with the proper kernel of integral transformation. To remedy this error, two correction kernels to the Stokes kernel were derived: the first in both closed and spectral forms and the second only in spectral form. Contributions from the first correction kernel to the geoid across the globe were [−0.867 m, +1.002 m] in the low-frequency domain implied by the GRIM4-S4 purely satellite-derived geopotential model. It is a few centimeters, on average, in the high-frequency domain with some exceptions of a few meters in places of high topographical relief and sizable geological features in accordance with the EGM96 combined geopotential model. The contributions from the second correction kernel to the geoid are [−0.259 m, +0.217 m] and [−0.024 m, +0.023 m] in the low- and high-frequency domains, respectively.

Waveform inversion for seismic source processes using ABIC with two sorts of prior constraints: Comparison between proper and improper formulations

For inversion analysis using Akaike's Bayesian Information Criterion (ABIC) we obtained a proper formulation to incorporate two sorts of partially‐dependent prior information into observed data by Bayes' rule. In previous improper formulations, complete independence of the two sorts of prior information has been assumed. Through comparison of the solutions obtained by the improper formulation with those by the proper formulation, we demonstrated the validity of the proper formulation. The results show that the previous improper formulation gives proper solutions, if and only if the data used for inversion are accurate and sufficient. If the data are inaccurate and/or insufficient, the improper formulation gives somewhat biased and oversimplified solutions. From a poor data set, if we employed the improper formulation, we could not find any solution because of the vanishing of the local minimum of ABIC.

Nutrients and grazing in modeling the deep chlorophyll maximum

A representation of nutrients uptake and grazing processes, based on the specific uptake rate of multiple nutrients and specific predation rate in 1-predator_ n-prey systems, is applied to a model for simulation of deep-chlorophyll maximum (DCM) in seas. In the original model a formulation for uptake processes was obtained from a mononutrient system. A detailed analysis of differences between the original and a modified model is performed. The modification increases the peak, but does not change the depth of DCM. Replacing the expression for grazing processes contributed to the differences between results more than a change in the uptake formulation. This is a consequence of two facts, (a) nutrient cycling plays a secondary role in the model, making nitrate dominant and ammonium a superfluous variable; while (b) prey concentrations are closer to their half-saturation constants. Since the original model was calibrated using improper formulations in uptake and grazing processes, a new calibration was performed.

Effect of Cyclodextrins on Topical Drug Delivery to the Eye

Cyclodextrins are oligosaccharides which form a new group of pharmaceutical excipients. Cyclodextrins have been added to aqueous eye drop preparations to solubilize lipophilic water-insoluble drug, to increase the chemical stability of drugs, or to reduce local drug irritation in the eye. Hydrophilic cyclodextrins, such as 2-hydroxypropyl-β-cyclodextrin, have been shown to be nontoxic to the eye and are generally well tolerated in aqueous eye drop formulations. However, improper formulation of aqueous cyclodextrin containing eye drop solutions can reduce the topical availability of the drug molecule. This paper reviews the effects of cyclodextrins and aqueous cyclodextrin eye drop formulations on the ocular bioavailability of drugs.