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1.
J Appl Lab Med ; 8(1): 23-33, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36610426

RESUMO

BACKGROUND: Risk analysis can be used to determine control limits for quality control (QC). The Parvin model is the most commonly used method for risk analysis; however; the Parvin model rests on assumptions that have been shown to produce paradoxical results and to underestimate risk. There is a need for an improved framework for risk analysis. METHODS: We developed a dynamic model (Markov Reward Model) to analyze the long-term behavior of an assay under the influence of a QC monitoring system. The model is flexible and accounts for different patterns of assay behavior (shift frequency, shift distribution) and the impact of error on patient outcomes. The model determines the distribution of undetected reported errors and the frequency of false-positive laboratory results as a function of QC settings. The model accounts for the competing risks (false detections, shifts in the mean) that cause an assay to move from an in-control state to an out-of-control state. RESULTS: The model provides a tradeoff curve that expresses the cost to prevent an unacceptable reported result in terms of laboratory cost (false-positive QC). The model can be used to optimize settings of a particular QC method or to compare the performance of different methods. CONCLUSIONS: We developed a method to evaluate that determines the cost to reduce the risk to patients (reported results with unacceptable errors) in terms of laboratory costs (false-positive QC).


Assuntos
Laboratórios , Humanos , Controle de Qualidade , Medição de Risco
2.
Materials (Basel) ; 16(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36614782

RESUMO

This study focused on the microstructural analysis, superplasticity, modeling of superplastic deformation behavior, and superplastic forming tests of the Al-Mg-Si-Cu-based alloy modified with Fe, Ni, Sc, and Zr. The effect of the thermomechanical treatment with various proportions of hot/cold rolling degrees on the secondary particle distribution and deformation behavior was studied. The increase in hot rolling degree increased the homogeneity of the particle distribution in the aluminum-based solid solution that improved superplastic properties, providing an elongation of ~470-500% at increased strain rates of (0.5-1) × 10-2 s-1. A constitutive model based on Arrhenius and Beckofen equations was used to describe and predict the superplastic flow behavior of the alloy studied. Model complex-shaped parts were processed by superplastic forming at two strain rates. The proposed strain rate of 1 × 10-2 s-1 provided a low thickness variation and a high quality of the experimental parts. The residual cavitation after superplastic forming was also large at the low strain rate of 2 × 10-3 s-1 and significantly smaller at 1 × 10-2 s-1. Coarse Al9FeNi particles did not stimulate the cavitation process and were effective to provide the superplasticity of alloys studied at high strain rates, whereas cavities were predominately observed near coarse Mg2Si particles, which act as nucleation places for cavities during superplastic deformation and forming.

3.
J Cogn ; 6(1): 8, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36698783

RESUMO

The dynamics of congruency effects in conflict tasks can be analyzed by means of delta plots which depict the reaction-time differences between incongruent and congruent conditions across the quantiles of the reaction-time distributions. Delta plots exhibit a variety of different shapes. Here we test the hypothesis that staggered onsets of processing task-relevant and task-irrelevant features for response selection (together with a declining influence of the irrelevant feature) produce such variety. For this purpose, staggered onsets were implemented in two extensions of the Leaky, Competing Accumulator model. We show the cardinal capability of these models to produce different shapes of delta plots with different assumptions about temporal offsets between processing relevant and irrelevant stimulus features. Applying the models to experimental data, we first show that they can reproduce the delta plots observed with a conflict task with stimulus size as the irrelevant feature. For this task congruency effects are delayed and appear only at longer reaction times. Second, we fit the models to the results of two new Simon-task experiments with an experimentally controlled temporal offset in addition to the internal one. The experimentally induced variations of the shape of delta plots for this task could be reasonably well fitted by one of the two models that assumed an early start of response selection as soon as either the relevant or the irrelevant stimulus feature becomes available. We conclude that delta plots are crucially shaped by staggered onsets of processing relevant and irrelevant features for response selection.

4.
Comput Biol Med ; 153: 106510, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36630829

RESUMO

SARS-CoV-2 has caused tremendous deaths globally. It is of great value to predict the evolutionary direction of SARS-CoV-2. In this paper, we proposed a novel mathematical model that could predict the evolutionary trend of SARS-CoV-2. We focus on the mutational effects on viral assembly capacity. A robust coarse-grained mathematical model is constructed to simulate the virus dynamics in the host body. Both virulence and transmissibility can be quantified in this model. A delicate equilibrium point that optimizes the transmissibility can be numerically obtained. Based on this model, the virulence of SARS-CoV-2 might further decrease, accompanied by an enhancement of transmissibility. However, this trend is not continuous; its virulence will not disappear but remains at a relatively stable range. A virus assembly model which simulates the virus packing process is also proposed. It can be explained why a few mutations would lead to a significant divergence in clinical performance, both in the overall particle formation quantity and virulence. This research provides a novel mathematical attempt to elucidate the evolutionary driving force in RNA virus evolution.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Modelos Teóricos
5.
Acta Trop ; 239: 106837, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36657506

RESUMO

Aedes aegypti is one of the most dominant mosquito species in the urban areas of Miami-Dade County, Florida, and is responsible for the local arbovirus transmissions. Since August 2016, mosquito traps have been placed throughout the county to improve surveillance and guide mosquito control and arbovirus outbreak response. In this paper, we develop a deterministic mosquito population model, estimate model parameters by using local entomological and temperature data, and use the model to calibrate the mosquito trap data from 2017 to 2019. We further use the model to compare the Ae. aegypti population and evaluate the impact of rainfall intensity in different urban built environments. Our results show that rainfall affects the breeding sites and the abundance of Ae. aegypti more significantly in tourist areas than in residential places. In addition, we apply the model to quantitatively assess the effectiveness of vector control strategies in Miami-Dade County.

6.
Cell Syst ; 14(1): 24-40.e11, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36657390

RESUMO

Biological systems can maintain memories over long timescales, with examples including memories in the brain and immune system. It is unknown how functional properties of memory systems, such as memory persistence, can be established by biological circuits. To address this question, we focus on transgenerational epigenetic inheritance in Caenorhabditis elegans. In response to a trigger, worms silence a target gene for multiple generations, resisting strong dilution due to growth and reproduction. Silencing may also be maintained indefinitely upon selection according to silencing levels. We show that these properties imply the fine-tuning of biochemical rates in which the silencing system is positioned near the transition to bistability. We demonstrate that this behavior is consistent with a generic mechanism based on competition for synthesis resources, which leads to self-organization around a critical state with broad silencing timescales. The theory makes distinct predictions and offers insights into the design principles of long-term memory systems.


Assuntos
Proteínas de Caenorhabditis elegans , Epigênese Genética , Animais , Epigênese Genética/genética , Inativação Gênica , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Padrões de Herança
7.
Entropy (Basel) ; 25(1)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36673275

RESUMO

Rotating-disc electrodes (RDEs) are favored technologies for analyzing electrochemical processes in electrically charged cells and other revolving machines, such as engines, compressors, gearboxes, and generators. The model is based on the concept of the nonlinear entropy convection-diffusion equations, which are constructed using semi-boundaries as an infinite notion. In this model, the surrogate solutions with different parameter values for the mathematical characterization of non-dimensional OH- and H+ ion concentrations at a rotating-disc electrode (RDE) are investigated using an intelligent hybrid technique by utilizing neural networks (NN) and the Levenberg-Marquardt algorithm (LMA). Reference solutions were calculated using the RK-4 numerical method. Through the training, validation, and testing sampling of reference solutions, the NN-BLMA approximations were recorded. Error histograms, absolute error, curve fitting graphs, and regression graphs validated the NN-BLMA's resilience and accuracy for the problem. Additionally, the comparison graphs between the reference solution and the NN-BLMA procedure established that our paradigm is reliable and accurate.

8.
Healthcare (Basel) ; 11(2)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36673628

RESUMO

In 2020, coronavirus (COVID-19) was declared a global pandemic and it remains prevalent today. A necessity to model the transmission of the virus has emerged as a result of COVID-19's exceedingly contagious characteristics and its rapid propagation throughout the world. Assessing the incidence of infection could enable policymakers to identify measures to halt the pandemic and gauge the required capacity of healthcare centers. Therefore, modeling the susceptibility, exposure, infection, and recovery in relation to the COVID-19 pandemic is crucial for the adoption of interventions by regulatory authorities. Fundamental factors, such as the infection rate, mortality rate, and recovery rate, must be considered in order to accurately represent the behavior of the pandemic using mathematical models. The difficulty in creating a mathematical model is in identifying the real model variables. Parameters might vary significantly across models, which can result in variations in the simulation results because projections primarily rely on a particular dataset. The purpose of this work was to establish a susceptible-exposed-infected-recovered (SEIR) model describing the propagation of the COVID-19 outbreak throughout the Kingdom of Saudi Arabia (KSA). The goal of this study was to derive the essential COVID-19 epidemiological factors from actual data. System dynamics modeling and design of experiment approaches were used to determine the most appropriate combination of epidemiological parameters and the influence of COVID-19. This study investigates how epidemiological variables such as seasonal amplitude, social awareness impact, and waning time can be adapted to correctly estimate COVID-19 scenarios such as the number of infected persons on a daily basis in KSA. This model can also be utilized to ascertain how stress (or hospital capacity) affects the percentage of hospitalizations and the number of deaths. Additionally, the results of this study can be used to establish policies or strategies for monitoring or restricting COVID-19 in Saudi Arabia.

9.
Artigo em Inglês | MEDLINE | ID: mdl-36673929

RESUMO

The public sector is becoming increasingly appealing. In the context of declining public money to support health studies and public health interventions, public-private partnerships with entities (including government agencies and scientific research institutes) are becoming increasingly important. When forming this type of cooperation, the participants highlight synergies between the private partners and the public's missions or goals. The tasks of private and public sector actors, on the other hand, frequently diverge significantly. The integrity and honesty of public officials, institutions, trust, and faith in those individuals and institutions may all be jeopardized by these collaborations. In this study, we use the institutional corruption framework to highlight systemic concerns raised by PPPs affiliated with the governments of one of South Asia's countries. Overall analytical frameworks for such collaborations tend to downplay or disregard these systemic impacts and their ethical implications, as we argue. We offer some guidelines for public sector stakeholders that want to think about PPPs in a more systemic and analytical way. Partnership as a default paradigm for engagement with the private sector needs to be reconsidered by public sector participants. They also need to be more vocal about which goals they can and cannot fulfill, given the limitations of public financing resources.


Assuntos
Saúde Pública , Parcerias Público-Privadas , Humanos , Setor Público , Governo , Medição de Risco
10.
Math Biosci Eng ; 20(1): 587-612, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36650780

RESUMO

There is an ongoing debate on the different transmission modes of SARS-CoV-2 and their relative contributions to the pandemic. In this paper, we employ a simple mathematical model, which incorporates both the human-to-human and environment-to-human transmission routes, to study the transmission dynamics of COVID-19. We focus our attention on the role of airborne transmission in the spread of the disease in a university campus setting. We conduct both mathematical analysis and numerical simulation, and incorporate published experimental data for the viral concentration in the air to fit model parameters. Meanwhile, we compare the outcome to that of the standard SIR model, utilizing a perturbation analysis in the presence of multiple time scales. Our data fitting and numerical simulation results show that the risk of airborne transmission for SARS-CoV-2 strongly depends on how long the virus can remain viable in the air. If the time for this viability is short, the airborne transmission route would be inconsequential in shaping the overall transmission risk and the total infection size. On the other hand, if the infectious virus can persist in aerosols beyond a few hours, then airborne transmission could play a much more significant role in the spread of COVID-19.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Aerossóis e Gotículas Respiratórios , Modelos Teóricos
11.
Math Biosci Eng ; 20(1): 656-682, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36650783

RESUMO

The emergence and growth of drug-resistant cancer cell subpopulations during anti-cancer treatment is a major challenge for cancer therapies. Combination therapies are usually applied for overcoming drug resistance. In the present paper, we explored the evolution outcome of tumor cell populations under different combination schedules of chemotherapy and p53 vaccine, by construction of replicator dynamical model for sensitive cells, chemotherapy-resistant cells and p53 vaccine-resistant cells. The local asymptotic stability analysis of the evolutionary stable points revealed that cancer population could evolve to the population with single subpopulation, or coexistence of sensitive cells and p53 vaccine-resistant cells, or coexistence of chemotherapy-resistant cells and p53 vaccine-resistant cells under different monotherapy or combination schedules. The design of adaptive therapy schedules that maintain the subpopulations under control is also demonstrated by sequential and periodic application of combination treatment strategies based on the evolutionary velocity and evolutionary absorbing regions. Applying a new replicator dynamical model, we further explored the supportive effects of sensitive cancer cells on targeted therapy-resistant cells revealed in mice experiments. It was shown that the supportive effects of sensitive cells could drive the evolution of cell population from sensitive cells to coexistence of sensitive cells and one type of targeted therapy-resistant cells.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Neoplasias , Animais , Camundongos , Proteína Supressora de Tumor p53 , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Terapia Combinada , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
12.
J Clin Med ; 12(2)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36675528

RESUMO

Translational research in medicine, defined as the transfer of knowledge and discovery from the basic sciences to the clinic, is typically achieved through interactions between members across scientific disciplines to overcome the traditional silos within the community. Thus, translational medicine underscores 'Team Medicine', the partnership between basic science researchers and clinicians focused on addressing a specific goal in medicine. Here, we highlight this concept from a City of Hope perspective. Using cisplatin resistance in non-small cell lung cancer (NSCLC) as a paradigm, we describe how basic research scientists, clinical research scientists, and medical oncologists, in true 'Team Science' spirit, addressed cisplatin resistance in NSCLC and identified a previously approved compound that is able to alleviate cisplatin resistance in NSCLC. Furthermore, we discuss how a 'Team Medicine' approach can help to elucidate the mechanisms of innate and acquired resistance in NSCLC and develop alternative strategies to overcome drug resistance.

13.
Molecules ; 28(2)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36677610

RESUMO

Compared with traditional oral and injection administration, the transdermal administration of traditional Chinese medicine has distinctive characteristics and advantages, which can avoid the "first pass effect" of the liver and the destruction of the gastrointestinal tract, maintain a stable blood concentration, and prolong drug action time. However, the basic theory and technology research in transdermal drug delivery are relatively limited at present, especially regarding research on new carriers of transdermal drug delivery and pharmacokinetic studies of the skin, which has become a bottleneck of transdermal drug delivery development. Triptolide is one of the main active components of Tripterygium wilfordii, which displays activities against mouse models of polycystic kidney disease and pancreatic cancer but its physical properties and severe toxicity limit its therapeutic potential. Due to the previously mentioned advantages of transdermal administration, in this study, we performed a detail analysis of the pharmacokinetics of a new transdermal triptolide delivery system. Triptolide nanoemulsion gels were prepared and served as new delivery systems, and the ex vivo characteristics were described. The metabolic characteristics of the different triptolide transdermal drug delivery formulations were investigated via skin-blood synchronous microdialysis combined with LC/MS. A multiscale modeling framework, molecular dynamics and finite element modeling were adopted to simulate the transport process of triptolide in the skin and to explore the pharmacokinetics and mathematical patterns. This study shows that the three-layer model can be used for transdermal drug delivery system drug diffusion research. Therefore, it is profitable for transdermal drug delivery system design and the optimization of the dosage form. Based on the drug concentration of the in vivo microdialysis measurement technology, the diffusion coefficient of drugs in the skin can be more accurately measured, and the numerical results can be verified. Therefore, the microdialysis technique combined with mathematical modeling provides a very good platform for the further study of transdermal delivery systems. This research will provide a new technology and method for the study of the pharmacokinetics of traditional Chinese medicine transdermal drug delivery. It has important theoretical and practical significance in clarifying the metabolic transformation of percutaneous drug absorption and screening for appropriate drugs and dosage forms of transdermal drug delivery.


Assuntos
Absorção Cutânea , Pele , Camundongos , Animais , Administração Cutânea , Pele/metabolismo , Sistemas de Liberação de Medicamentos
14.
Vaccines (Basel) ; 11(1)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36679972

RESUMO

In this work, we develop mathematical models of the immune response to respiratory viral infection, taking into account some particular properties of the SARS-CoV infections, cytokine storm and vaccination. Each model consists of a system of ordinary differential equations that describe the interactions of the virus, epithelial cells, immune cells, cytokines, and antibodies. Conventional analysis of the existence and stability of stationary points is completed by numerical simulations in order to study the dynamics of solutions. The behavior of the solutions is characterized by large peaks of virus concentration specific to acute respiratory viral infections. At the first stage, we study the innate immune response based on the protective properties of interferon secreted by virus-infected cells. Viral infection down-regulates interferon production. This competition can lead to the bistability of the system with different regimes of infection progression with high or low intensity. After that, we introduce the adaptive immune response with antigen-specific T- and B-lymphocytes. The resulting model shows how the incubation period and the maximal viral load depend on the initial viral load and the parameters of the immune response. In particular, an increase in the initial viral load leads to a shorter incubation period and higher maximal viral load. The model shows that a deficient production of antibodies leads to an increase in the incubation period and even higher maximum viral loads. In order to study the emergence and dynamics of cytokine storm, we consider proinflammatory cytokines produced by cells of the innate immune response. Depending on the parameters of the model, the system can remain in the normal inflammatory state specific for viral infections or, due to positive feedback between inflammation and immune cells, pass to cytokine storm characterized by the excessive production of proinflammatory cytokines. Finally, we study the production of antibodies due to vaccination. We determine the dose-response dependence and the optimal interval of vaccine dose. Assumptions of the model and obtained results correspond to the experimental and clinical data.

15.
J Chromatogr A ; 1691: 463824, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36709549

RESUMO

Liquid-liquid chromatography (LLC) is a technique in which the separation of mixture components is achieved due to their different distribution between the two phases of a pre-equilibrated biphasic solvent system. In this work, the LLC operation in the nonlinear range of the distribution isotherm was systematically examined for the first time. The influence of the feed concentration on the elution profiles of a model component (cannabidiol, CBD) was studied in three LLC units of different types and sizes ranging from ∼20 mL to ∼2 L. A series of pulse injections with CBD concentrations varying from 1 to 300 mg/mL was performed with n-hexane/methanol/water 5/4/1 (v/v/v) in descending mode (lower phase as the mobile phase). The elution profiles were simulated using the equilibrium-cell model and an anti-Langmuir-like equation for describing the CBD distribution equilibria. The distribution equilibria equation parameters were fitted to the CBD elution profiles using the peak fitting method. The model was validated and provided good predictions of the CBD elution profiles in the entire concentration range for all three LLC units.

16.
Theory Biosci ; 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36710290

RESUMO

The aim of this study was an analytical justification of the emergence and presence of the phenomenon of war among hominins, taking into account males' genetic benefits gained through war in the natural environment. Based on chimpanzee behavior, the analytical model of the primary warrior balance was explored, comparing the risk of a war expedition with the genetic profits from war rape-"life and death balance". On the profits side, genetic gains possible to obtain in terms of permanent attractiveness of females (warrior status and abductions of females) were also included. Kin cooperation, parochial altruism, and "partisan strategy" have been defined as psychological mechanisms that enable effective group violence. Male genetic benefit from a war rape could exceed the risk of a warrior's death in the chimpanzee-human LCA species; transition from the herd to the patriarchal tribal social system could increase warrior's genetic gains from war. At the root of war lie sexual limitations of cooperating males, induced by female sexual preferences and lack of the permanent female sexual drive. War rape allows reproductive success for dominated and thus sexually restricted males. Tendencies for group aggression to gain access to out-group females (the war gene) are common among sexually restricted men. Resource-rich areas favor increase in human population density, this affects group territoriality and promotes intergroup conflicts, and thus patriarchy. Roots of conventional patriarchal marriage are strongly combined with war-"the right to land entails the right to a female".

17.
J Virol ; 97(1): e0129422, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36602363

RESUMO

Potassium (K+) is one of the most abundant cations in the human body. Under normal conditions, the vast majority of K+ is found within cells, and the extracellular [K+] is tightly regulated to within 3.0 to 5.0 mM. However, it has recently been shown that high levels of localized necrosis can increase the extracellular concentration of K+ to above 50 mM. This raises the possibility that elevated extracellular K+ might influence a variety of biological processes that occur within regions of necrotic tissue. For example, K+ has been shown to play a central role in the replication cycles of numerous viral families, and in cases of lytic infection, localized regions containing large numbers of necrotic cells can be formed. Here, we show that the replication of the model poxvirus myxoma virus (MYXV) is delayed by elevated levels of extracellular K+. These increased K+ concentrations alter the cellular endocytic pathway, leading to increased phagocytosis but a loss of endosomal/lysosomal segregation. This slows the release of myxoma virus particles from the endosomes, resulting in delays in genome synthesis and infectious particle formation as well as reduced viral spread. Additionally, mathematical modeling predicts that the extracellular K+ concentrations required to impact myxoma virus replication can be reached in viral lesions under a variety of conditions. Taken together, these data suggest that the extracellular [K+] plays a role in determining the outcomes of myxoma infection and that this effect could be physiologically relevant during pathogenic infection. IMPORTANCE Intracellular K+ homeostasis has been shown to play a major role in the replication of numerous viral families. However, the potential impact of altered extracellular K+ concentrations is less well understood. Our work demonstrates that increased concentrations of extracellular K+ can delay the replication cycle of the model poxvirus MYXV by inhibiting virion release from the endosomes. Additionally, mathematical modeling predicts that the levels of extracellular K+ required to impact MYXV replication can likely be reached during pathogenic infection. These results suggest that localized viral infection can alter K+ homeostasis and that these alterations might directly affect viral pathogenesis.

18.
J Food Sci Technol ; 60(1): 353-360, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36618057

RESUMO

Contamination by pathogenic bacteria is the major cause of foodborne diseases, which is an international public health issue. Probiotics added to fermented milk can fight against these pathogens. This research aimed to evaluate, by mathematical models, the behaviour of Lactobacillus acidophilus against pathogenic strains inoculated in goat milk yogurt. The Baranyi and Roberts' model was adjusted to data and statistically evaluated. A greater pathogens reduction occurred in the samples supplemented with probiotics, which exhibited antimicrobial activity against Pseudomonas aeruginosa. The reduction was less efficient against Escherichia coli. The primary models adjustment indicated that the Baranyi and Roberts fitted the reduction of P. aeruginosa, Salmonella typhimurium, E. coli and Staphylococcus aureus inactivation. The addition of L. acidophilus proved to be an effective alternative for the safer production of goat milk yogurt.

19.
Drug Metab Dispos ; 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36623886

RESUMO

Clearances are important parameters in pharmacokinetic (PK) models. All clearances in PK models are either process clearances that include diffusion, transport and metabolism clearances, or system clearances that include organ and systemic clearance. Clearance and volume of distribution are two independent parameters that characterize drug disposition in both individual compartments and systems of compartments. In this minireview, we show that systemic and organ clearances are net clearances that can be easily derived by partition analysis. When drugs are eliminated from the central compartment by first order processes, systemic clearance is constant. When drugs are eliminated from a peripheral compartment, instantaneous systemic clearance will vary with time. However, average clearance and clearance at steady state will be constant and will equal dose divided by area under the curve. We show that peripheral elimination will not have a large impact on most pharmacokinetic analyses and that standard models of organ and systemic clearance are useful and appropriate. Significance Statement There are two basic kinds of clearances used in pharmacokinetic models, process and system clearances. We show that organ and systemic clearances are net clearances with blood or plasma as the driving concentration. For linear pharmacokinetics, clearance is constant for elimination from the central compartment but varies with time for peripheral elimination. Despite the different kinds of clearance parameters and models, standard clearance models and concepts remain valid.

20.
J Hazard Mater ; 445: 130554, 2023 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-36635918

RESUMO

This study presents a mathematical model describing the adsorption-desorption process of water dissolved elements onto reactive porous materials during filtering operations performed under dynamic flow conditions. The developed model is based on a reversible second order adsorption kinetic featuring the progressive reduction of the purifying capacity of the filtering material due to the gradual exhaustion of the active sites available for solute retention. It enables the simulation of the performances of water filtering systems through the use of parameters having a clear chemical-physical significance or it can be used for the estimation of these parameters to characterize the adsorption properties of the reactive material. Starting from the same adsorptive conceptual model used for the filtering system marked by ongoing flowing conditions, an adaptation for static systems was performed on the mathematical framework in order to process the same chemical physical parameters in both schemes. Adsorption laboratory tests were carried out to validate the developed model. Results show that the kinetic constants and adsorption capacities (a maximum of about 45 mg g-1 was obtained for the tested material) are highly comparable, both within the same experimental system, and between different experimental setup. This confirms the validity of the developed model which is able to perfectly fit the observed concentration data in all tested configurations.

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