Risk of false conformity decisions due to measurement uncertainty of Active Pharmaceutical Ingredient: A multiparametric evaluation

Abstract Medicines must be subject to physical, chemical, and biological analysis to guarantee their quality, safety, and effectiveness. Despite the efforts to ensure the reliability of analytical results, some uncertainty will always be associated with the measured value, which can lead to false decisions regarding conformity/non-conformity assessment. This work aims to calculate the specific risk of false decisions regarding conformity/non-conformity of acetaminophen oral solution dosage form. The acetaminophen samples from five different manufacturers (A, B, C, D, and E) were subject to an active pharmaceutical ingredient assay, density test, and dose per drop test according to the official compendia. Based on measured values and their respective uncertainties, the risk values were calculated using the Monte Carlo method implemented in an MS Excel spreadsheet. The results for two acetaminophen oral solution samples (C and D) provided an increased total risk value of false acceptance (33.1% and 9.6% for C and D, respectively). On the other hand, the results for the other three acetaminophen samples (A, B, and E) provided a negligible risk of false acceptance (0.004%, 0.025%, and 0.045% for A, B, and E, respectively). This indicates that measurement uncertainty is very relevant when a conformity assessment is carried out, and information on the risks of false decisions is essential to ensure proper decisions.

Nonparametric item response models: a comparison on recovering true scores / Modelos de resposta ao item não-paramétricos: comparando a recuperação de escores verdadeiros / Modelos de respuesta al item no-paramétricos: comparando la recuperación de puntuaciones verdaderas

Nonparametric procedures are used to add flexibility to models. Three nonparametric item response models have been proposed, but not directly compared: the Kernel smoothing (KS-IRT); the Davidian-Curve (DC-IRT); and the Bayesian semiparametric Rasch model (SP-Rasch). The main aim of the present study is to compare the performance of these procedures in recovering simulated true scores, using sum scores as benchmarks. The secondary aim is to compare their performances in terms of practical equivalence with real data. Overall, the results show that, apart from the DC-IRT, which is the model that performs the worse, all the other models give results quite similar to those when sum scores are used. These results are followed by a discussion with practical implications and recommendations for future studies.(AU)

Procedimentos não paramétricos são usados para adicionar flexibilidade aos modelos. Três modelos não paramétricos de resposta ao item foram propostos, mas não comparados diretamente: o Kernel smoothing (KS-IRT); a Curva Davidiana (DC-IRT); e o modelo semiparamétrico Rasch Bayesiano (SP-Rasch). O objetivo principal do presente estudo é comparar o desempenho desses procedimentos na recuperação de escores verdadeiros simulados, utilizando escores de soma como benchmarks. O objetivo secundário é comparar seus desempenhos em termos de equivalência prática com dados reais. De forma geral, os resultados mostram que, além do DC-IRT, que é o modelo que apresenta o pior desempenho, todos os outros modelos apresentam resultados bastante semelhantes aos de quando se usam somatórios. Esses resultados são seguidos de uma discussão com implicações práticas e recomendações para estudos futuros.(AU)

Se utilizan procedimientos no paramétricos para agregar flexibilidad a los modelos. Se propusieron tres modelos de respuesta al ítem no paramétricos, pero no se compararon directamente: Kernel smoothing (KS-IRT); la curva davidiana (DC-IRT); y el modelo bayesiano de Rasch semiparamétrico (SP-Rasch). El objetivo principal del presente estudio es comparar el desempeño de estos procedimientos en la recuperación de puntajes verdaderos simulados, utilizando puntajes de suma como puntos de referencia. El objetivo secundario es comparar su desempeño en términos de equivalencia práctica con datos reales. En general, los resultados muestran que, a excepción de DC-IRT, que es el modelo con peor desempeño, todos los otros modelos presentan resultados bastante similares a los obtenidos cuando se utilizan sumatorios. Estos resultados son seguidos por una discusión con implicaciones prácticas y recomendaciones para estudios futuros.(AU)

Propuesta metodológica para el uso del programa PCXMC 2.0 en modalidad rotacional / Methodological Proposal for the use of the program PCXMC 2.0 in Rotational Mode

RESUMEN Durante los procedimientos intervencionistas que utilizan fluoroscopia, se entrega a los pacientes diferentes niveles de dosis de radiación, que pueden tener un impacto a corto, mediano o largo plazo, así como en su severidad. Esto en función del tipo de radiación utilizada y de la sensibilidad a la radiación del tipo(s) de órgano(s) irradiado, es en este punto que se vuelve determinante conocer la dosis a órganos entregada durante los procedimientos con el fin de asegurar el bienestar de los pacientes, este procedimiento no se puede realizar directamente en los órganos del paciente, por lo que se utilizan programas especializado en cálculos dosimétricos. El software PCXMC 2.0 logra estimar la dosis efectiva a través del método determinístico Monte Carlo, a su vez, agregando la dosis equivalente y evaluación de riesgo para estudios dosimétricos, por lo cual, el objetivo del presente trabajo fue proponer una metodología estandarizada para la utilización del programa PCXMC en el cálculo de estas dos magnitudes

ABSTRACT During interventional procedures that utilize fluoroscopy, patients are exposed to varying levels of radiation doses, which can have short, medium, or long term impacts, as well as varying severities. This depends on the type of radiation used and the radiation sensitivity of the organ(s) being irradiated. At this point, it becomes crucial to determine the organ doses delivered during procedures in order to ensure patient well-being. Since direct measurements cannot be made on the patient's organs, specialized software is used for dosimetric calculations. PCXMC 2.0 software achieves the estimation of effective dose through the deterministic Monte Carlo method, while also incorporating equivalent dose and risk assessment for dosimetric studies. Therefore, the objective of this work was to propose a standardized methodology for the use of the PCXMC 2.0 sofware in the calculation of these two magnitudes.it is important to outline a working method for this software and provide instructions on its operation

Monte Carlo simulation of α recoil migration of plutonium aerosol / 中国辐射卫生

Objective To evaluate the migration of plutonium aerosol caused by α recoil. Methods In this paper, the recoil deposition and Brownian motion of plutonium-containing nanoaerosols were simulated by Monte Carlo method. The recoil angle and the vertical first landing time of Brownian motion in the process of settling were sampled, and then the lateral displacements of Brownian motion were sampled to determine the final settling position of aerosol. Results For aerosols with particle sizes of 10-50 nm, the maximum migration distance of a single recoil settling was 1.39 μm. Brownian motion increased the migration capacity. Although there was a high likelihood that aerosols settled within 100 μm, there remained a slight probability of long-term suspension in the air. Conclusion The α recoil is one of the mechanisms of plutonium aerosol migration. An important mechanism for long-distance migration of nanoaerosols is that Brownian motion after recoil may cause them to suspend for a long time.

Coarse-Grained Simulation of Amyloid Nucleation under Cooperative Effects of Peptides / 医用生物力学

Objective To explore the cooperative effect from β-propensity of amyloidogenic peptides on amyloid nucleation and its related products. Methods Based on a coarse-grained model for amyloidogenic peptides containing two states ( a soluble state and a β-sheet-forming state), with the consideration of two kinds of cooperative effects on β-propensity of peptides ( inhibiting and promoting the conformational conversion of peptides), the regulation of cooperative effects from amyloidogenic peptides on amyloid nucleation was analyzed through Monte Carlo simulations. Results In the case of the cooperative effect inhibiting the conformational conversion of peptides, amyloid nucleation occurred only within a certain interval of the peptide concentration, as well as inside the oligomers with certain sizes. Besides, the coexistence of on-pathway and off-pathway oligomers was observed. In the case of the cooperative effect promoting the conformational conversion of peptides, the β-sheet protofibril could be observed at physiological concentration as low as 4 μmol / L. Conclusions In this study, a more realistic coarse-grained model for amyloidogenic peptides was developed by introducing the cooperative effects of local concentration on β-propensity of amyloidogenic peptides, with observation of some intriguing phenomena not reported in previous simulations. The research findings not only improve current understandings about the mechanism of amyloid formation, but also provide theoretic references for the therapeutic strategies for curing neurodegenerative diseases

Evaluation of the dosing regimen of meropenem in elderly patients with renal insufficiency with Monte Carlo simulation / 中国药房

OBJECTIVE To explore the appropriate dosing regimen of meropenem in the elderly with renal insufficiency. METHODS The meropenem population pharmacokinetics of the two-compartment model of elderly patients were applied for Monte Carlo simulation. The model included the effect of renal function on the parameters. The designed dosages were 0.5， 1， 2 g； the administration modes included intravenous injection （lasting for 6 min） and intravenous drip （0.5， 3 h）； the administration frequencies were q12 h， q8 h. A total of 18 dosing regimens were designed. The probability of target attainment of %fT＞4MIC≥40% and Cmin≤27.5 mg/L were calculated respectively to optimize the dosing regimen. RESULTS For elderly patients with creatinine clearance （CLcr） ≤40 mL/min， when the minimum inhibitory concentration （MIC） was equaled to 1 mg/L， the suggested dosing regimens were “0.5 g， intravenous drip 0.5 h， q12 h”“ 1 g， intravenous injection， q12 h”. When the MIC was equaled to 2 mg/L， the suggested dosing regimens were “0.5 g， intravenous injection， q8 h”“ 1 g， intravenous drip 0.5 h， q12 h”. When the MIC was equaled to 4， 8 mg/L， the suggested dosing regimens were “1 g （or 2 g）， intravenous injection， q8 h”. For elderly patients with CLcr equal to 50 mL/min， when the MIC was equaled to 1 mg/L， the suggested dosing regimens were “0.5 g， intravenous injection， q8 h“”1 g， intravenous injection， q12 h”. When the MIC was equal to 2， 4， 8 mg/L，the suggested dosing regimens were“0.5 g （or 1 g， or 2 g）， intravenous drip for 0.5 h， q8 h”. The appropriate dosing regimens of all the above protocols were above 96.6%. In the dosing regimen of “2 g，intravenous injection or intravenous drip 0.5 h， q8 h”， Cmin＞27.5 mg/L occurred in 40 times among the 1 000 times of simulation， indicating adverse reactions of the nervous system may occur. CONCLUSIONS For the elderly patients with renal insufficiency， the dosing regimen of meropenem should be adjusted accordingly with CLcr＝40 mL/min as the boundary， and the toxicity of nervous system should be considered at the same time.

Evaluation of tegacycline regimens in treatment of gram-negative bacterial infections with Monte Carlo simulation / 中国临床药理学与治疗学

AIM: To evaluate the dose regimens of tegacycline for treatment of hospital-acquired pneumonia, complex abdominal infection and complex skin and soft tissue infection caused by Gram-negative bacterial infections with Monte Carlo model. METHODS: The minimum inhibitory concentrations (MICs) of tegacycline against Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae were collected from the CHINET in 2018. The target probability (PTA) and cumulative response fraction (CFR) of different regimens were calculated using Monte Carlo simulation based on PK/PD theory of tegacycline. RESULTS:In the treatments of HAP caused by gram-negative bacteria, when MIC≤0.5 μg / mL, the PTA of 50 mg q12h was greater than 90%, and when MIC≥1 μg / mL, PTA and CFR of 100 mg q12h were both greater than 90%, When MIC≥2 μg/mL, 50 mg q12h, 75 mg q12h and 100 mg q12h doses of PTA were less than 90%. In the treatment of cIAI, when MIC≤0.5 μg / mL, PTA of 50 mg q12h reached the target value, and when MIC=1 μg/mL, PTA of 100 mg q12h was greater than 90%. For complex skin and soft tissue infection, when the MIC≤0.25 μg/mL, the PTA of 75 mg q12h and 100 mg q12h was greater than 90%, and the PTA of the three administration regimen was less than 90%, when the MIC≥0.5 μg/mL. CONCLUSION:The dose of 50 mg q12h is more suitable for the treatment of HAP, when MIC>0.5 μg/mL, tigecycline may need 100 mg q12h to obtain the best clinical efficacy in the treatment of cIAI. For cSSSI. when MIC≤0.25 μg/mL, tigecycline can be administered with 75 mg q12h and 100 mg q12h. For the three types of infections caused by Escherichia coli, the conventional dose of tigecycline may achieve clinical efficacy.

Monte Carlo simulation and analysis of eye lens dose of the first operator in interventional therapy / 中国辐射卫生

Objective To establish a model for estimating the eye lens dose of the first operator in interventional therapy based on the Monte Carlo simulation, and to provide a scientific basis for the rapid and accurate evaluation of the eye lens dose for radiation workers in interventional therapy. Methods Based on the MIRD phantom and eye model for adult Chinese males, the MCNPX program was used to establish the physical model to calculate the spatial distribution of radiation field and eye lens dose for the first operator. A GR200 Type A LiF (Mg, Cu, P) thermoluminescence dosimeter was used for experimental measurement to verify the simulation results. Results Monte Carlo simulation and experimental measurements showed that the spatial distribution of radiation field was symmetrical. Compared with the measured doses, the errors of the simulated eye lens dose of the first operator were between −8.3% and 7.3%. The dose of the left eye lens was higher than that of the right eye. Conclusion The Monte Carlo model constructed in this study initially realizes the simulation of eye lens dose of the first operator in interventional therapy. In the future, the model will be further optimized based on irradiation parameters such as exposure time, tube voltage, tube current, and projection direction used in clinic practice, so as to more accurately evaluate the eye lens dose of interventional therapy staff.

Evaluation of PET Mainstream Scattering Correction Methods / 中国医疗器械杂志

OBJECTIVE@#Current mainstream PET scattering correction methods are introduced and evaluated horizontally, and finally, the existing problems and development direction of scattering correction are discussed.@*METHODS@#Based on NeuWise Pro PET/CT products of Neusoft Medical System Co. Ltd. , the simulation experiment is carried out to evaluate the influence of radionuclide distribution out of FOV (field of view) on the scattering estimation accuracy of each method.@*RESULTS@#The scattering events produced by radionuclide out of FOV have an obvious impact on the spatial distribution of scattering, which should be considered in the model. The scattering estimation accuracy of Monte Carlo method is higher than single scatter simulation (SSS).@*CONCLUSIONS@#Clinically, if the activity of the adjacent parts out of the FOV is high, such as brain, liver, kidney and bladder, it is likely to lead to the deviation of scattering estimation. Considering the Monte Carlo scattering estimation of the distribution of radionuclide out of FOV, it's helpful to improve the accuracy of scattering distribution estimation.

Development of a simplified phantom for calibration of whole-body counter / 中国辐射卫生

Objective To develop a simplified phantom for the calibration of whole-body counters. Methods A simplified phantom design method for the calibration of whole-body counters was established based on the process and method of calibrating whole-body counters. By using the established method and Monte Carlo method, a simplified phantom including the total body, thyroid, lungs, and gastrointestinal tract was designed to calibrate the ORTEC-Stand FAST II whole-body counter. The simplified phantom was compared with the BOMAB phantom through experimental measurements. Results Within the range of 50 keV to 2 MeV, for rays of the same energy in the same organ of the simplified phantom and BOMAB phantom, the simulated data of detection efficiency by whole-body counting showed an error within 5%, and the experimental measurements showed an error within 10%. Conclusion We developed a simplified phantom for the calibration of the whole-body counter, demonstrating the feasibility of using the simplified phantom instead of a physical body phantom for whole-body counter calibration, which can greatly facilitate whole-body counter calibration for internal radiation monitoring.

Health risk assessment of chemical substances in drinking water in Shijiazhuang from 2014 to 2021 / 环境与职业医学

Background A variety of substances in drinking water are hazardous to human health and there are health risks associated with ingestion of these substances via drinking water. Objective To assess the carcinogenic and non-carcinogenic health risks of drinking water in Shijiazhuang from 2014 to 2021. Methods The collection, preservation, and testing of 10529 drinking water samples (including finished water and tap water) in Shijiazhuang were conducted from 2014 to 2021 and followed the Standard examination methods for drinking water (GB/T 5750—2006). The health risks of 15 chemicals in drinking water by oral exposure were assessed using the US Environmental Protection Agency's four-step method combined with Monte Carlo simulation. Results Among the 15 chemicals in drinking water assessed for their health risks at general exposure levels and high exposure levels via oral route in Shijiazhuang from 2014 to 2021, the leading three chemicals and related values of carcinogenic risks for adults were cadmium (1.11×10−4, 2.98×10−4), arsenic (5.88×10−5, 1.56×10−4), and chromium (5.48×10−5, 2.41×10−4), and the leading three chemicals and related values of non-carcinogenic risks were fluoride (3.57×10−1, 6.57×10−1), arsenic (1.31×10−1, 3.47×10−1), and nitrate (1.14×10−1, 5.98×10−1). The health risk values of trichloromethane and aluminum were elevated but still in acceptable ranges. Drinking water-associated health risk values were higher in males than in females, such as the cancer risk for general exposure levels of arsenic in men was 5.76×10−5, compared to 5.72×10−5 in women. The health risk values of cadmium, chromium, fluoride, nitrate, and other chemicals in ground water were higher than those of surface water, and the health risk values of trichloromethane and carbon tetrachloride were lower than those in surface water, such as the non-carcinogenic risk value for general exposure levels of fluoride in groundwater was 3.61×10−1, compared to 2.27×10−1 in surface water. Factors such as water transmission and distribution links, water period, and season affected the health risks of drinking water. The general exposure levels of trichloromethane in tap water had a higher carcinogenic risk of 1.75×10−7 compared with 8.17×10−8 in finished water. The general levels of arsenic exposure was higher in the dry season at 1.36×10−1, compared with 1.26×10−1 in the wet season. Conclusion Except that the carcinogenic risk of cadmium at general exposure levels in Shijiazhuang exceeds the maximum acceptable range recommended by US Environmental Protection Agency, the health risk values of the remaining 14 chemicals are below the maximum acceptable risk. The carcinogenic risk values of arsenic and chromium and the non-carcinogenic risk values of fluoride, arsenic, and nitrate are relatively high, but do not exceed the maximum acceptable ranges. The emphasis should be on the management of drinking water in highly exposed areas and populations.

Model construction and software design of computed tomography radiation system based on visualization / 生物医学工程学杂志

The Monte Carlo N-Particle (MCNP) is often used to calculate the radiation dose during computed tomography (CT) scans. However, the physical calculation process of the model is complicated, the input file structure of the program is complex, and the three-dimensional (3D) display of the geometric model is not supported, so that the researchers cannot establish an accurate CT radiation system model, which affects the accuracy of the dose calculation results. Aiming at these two problems, this study designed a software that visualized CT modeling and automatically generated input files. In terms of model calculation, the theoretical basis was based on the integration of CT modeling improvement schemes of major researchers. For 3D model visualization, LabVIEW was used as the new development platform, constructive solid geometry (CSG) was used as the algorithm principle, and the introduction of editing of MCNP input files was used to visualize CT geometry modeling. Compared with a CT model established by a recent study, the root mean square error between the results simulated by this visual CT modeling software and the actual measurement was smaller. In conclusion, the proposed CT visualization modeling software can not only help researchers to obtain an accurate CT radiation system model, but also provide a new research idea for the geometric modeling visualization method of MCNP.

Analysis of factors influencing the medical insurance balance of hospitalization expenses for gastric cancer surgery patients under DRG payment / 中华医院管理杂志

Objective:To analyze the influencing factors of the medical insurance balance of hospitalization expenses for gastric cancer surgery patients under DRG payment, for reference for promoting the reform of DRG payment in public hospitals and controlling hospitalization expenses reasonably.Methods:The gastric cancer patients enrolled in the gastroenterology department of a tertiary comprehensive hospital from January to July 2022 were selected as the research subjects. The indicators such as patient age, medical insurance balance, hospitalization expenses and their composition were extracted from the hospital information management system and the medical insurance settlement system a certain city. Descriptive analysis was conducted for all data, and stepwise multiple linear regression was used to analyze the influencing factors of patients′ medical insurance balance. Monte Carlo simulation method was used to simulate different combination scenarios of various influencing factors to analyze the probability of medical insurance balance.Results:A total of 205 patients were contained, including 117 in the medical insurance balance group and 88 in the loss group. The difference in hospitalization expenses and medical insurance balance between the two groups of patients were statistically significant ( P<0.05). The intervention of medical insurance specialists, correct DRG enrollment, parenteral nutrition preparation costs, anti infective drug costs, examination costs, and consumables costs were the influencing factors of patient medical insurance balance ( P<0.05). Through Monte Carlo simulation verification, patients with different cost parenteral nutrition preparations, or different anti infective drug schemes had the higher probability of medical insurance balance in the scenario where the medical insurance commissioner intervenes and the DRG enrollment was correct. Conclusions:The hospital adopted interventions from medical insurance specialists to ensure the correct DRG enrollment of patients, accurate use of parenteral nutrition and anti infective drugs, and reasonable control the cost of examinations and consumables, which could increase the probability of medical insurance balance for gastric cancer surgery patients. In the future, hospitals should further promote the procurement of drug consumables in bulk, reduce unnecessary examinations, develop standardized perioperative nutritional interventions and anti infection treatment pathways, ensure the accuracy of DRG enrollment, optimize clinical diagnosis and treatment pathways to improve the efficiency of medical insurance fund utilization and provide high-quality medical services for patients.

Contamination status and exposure risk of mycotoxins in Coicis Semen / 中国中药杂志

By investigating the contamination status and predicting the exposure risk of mycotoxin in Coicis Semen, we aim to provide guidance for the safety supervision of Chinese medicinal materials and the formulation(revision) of mycotoxin limit standards. The content of 14 mycotoxins in the 100 Coicis Semen samples collected from five major markets of Chinese medicinal materials in China was determined by UPLC-MS/MS. The probability evaluation model based on Monte Carlo simulation method was established after Chi-square test and One-way ANOVA of the sample contamination data. Health risk assessment was performed on the basis of margin of exposure(MOE) and margin of safety(MOS). The results showed that zearalenone(ZEN), aflatoxin B_1(AFB_1), deoxynivalenol(DON), sterigmatocystin(ST), and aflatoxin B_2(AFB_2) in the Coicis Semen samples had the detection rates of 84%, 75%, 36%, 19%, and 18%, and the mean contamination levels of 117.42, 4.78, 61.16, 6.61, and 2.13 μg·kg~(-1), respectively. According to the limit standards in the Chinese Pharmacopoeia(2020 edition), AFB_1, AFs and ZEN exceeded the standards to certain extents, with the over-standard rates of 12.0%, 9.0%, and 6.0%, respectively. The exposure risks of Coicis Semen to AFB_1, AFB2, ST, DON, and ZEN were low, while 86% of the samples were contaminated with two or more toxins, which needs more attention. It is suggested that the research on the combined toxicity of different mycotoxins should be strengthened to accelerate the cumulative exposure assessment of mixed contaminations and the formulation(revision) of toxin limit standards.

The Challenges And Pitfalls Of Limb-Leads And Heart-Axis Calculations - The Differences Between the Overall Magnitudes of Bipolar and Augmented Unipolar Leads cannot be Explained with the Ohm's Law

Summary Our paper analyses the interdependence between the overall magnitudes and resistances of bipolar and augmented unipolar limb leads of electrocardiograms. The findings strongly indicate that the overall ratio of magnitude of the bipolar and augmented unipolar limb leads is not a constant value, whereas the overall ratio of resistance is a constant value. These results expand but partially contradict a previous study. The ratio of the magnitude of bipolar leads to augmented unipolar leads is between 1 and 4/3 with a mean value of 2/?3, and this ratio is a function of the electrical axis of the heart. Our results also show that the overall ratio of resistance between bipolar and augmented unipolar limb leads approaches the value of 4/3. Conclusively, the ratio of magnitudes between limb leads is not a constant value, the ratio of resistances can be assumed as a constant value and therefore the difference of magnitudes between limb leads cannot be explained with the Ohm's law.

Eficácia in sílico do florfenicol no tratamento de pododermatite infecciosa por Fusobacterium necrophorum em ovelhas / In sílico efficacy of florfenicol in the treatment of Fusobacterium necrophorum infectious pododermatitis in sheep

Objetivou-se comparar o efeito in silico do florfenicol nas doses de 20 e 30 mg/Kg em ovinos pelas vias intravenosa (IV) e intramuscular (IM), usando a modelagem PK/PD. Realizou-se uma simulação de Monte Carlo com base nos dados de concentração plasmática de um estudo publicado anteriormente. Calculou-se a área sob a curva (ASC) e as taxas de eficácia do florfenicol para os efeitos bacteriostático, bactericida e de erradicação bacteriológica. A dose de 20 mg/Kg IV demonstrou efeitos de erradicação de 100, 93 e 0% para CIM de 0,5, 1 e acima, respectivamente. O efeito bacteriostático foi de 99 e 90% para CIM de 4 e 2 µg/ml, enquanto o bactericida foi de 14% para CIM de 2 µg/ml. A dose de 30 mg/Kg IV apresentou 100% de erradicação para CIM de 1 µg/mL e 100% de efeito bactericida para CIM de 2 µg/mL. Há 100% de efeito bacteriostático em CIM de 4 µg/ml. As doses de 20 e 30 mg/Kg IM mostraram 100% de erradicação para CIM até 1 µg/mL e 0% para CIM maiores. O efeito bacteriostático foi mantido em 100% para uma CIM de 4 µg/mL em ambas as doses. Este estudo mostra o efeito de erradicação bacteriológica do florfenicol nas doses de 20 e 30 mg/Kg, IV e IM. Recomenda-se que seja feito um estudo de eficácia in vivo com a dose de 30mg/Kg IM em ovinos infectados por F. necrophorum com MIC superior a 2 µg/mL.

We aimed to compare the in silico effect of florfenicol at doses of 20 and 30 mg/Kg in sheep by intravenous (IV) and intramuscular (IM) routes, using PK/PD modeling. We performed a Monte Carlo simulation based on plasma concentration data from a previously published study. We calculated the area under the curve (AUC) and the efficacy rates of florfenicol to bacteriostatic, bactericidal, and bacteriological eradication effects. The dose of 20 mg/Kg IV demonstrated 100, 93, and 0% eradication effects for MICs of 0.5, 1, and above, respectively. The bacteriostatic effect was 99 and 90% for MIC of 4 and 2 µg/ml, while the bactericide was 14% for MIC of 2 µg/ml. The 30 mg/Kg IV dose showed 100% eradication for MIC of 1 µg/mL and 100% bactericidal effect for MIC of 2 µg/mL. There is a 100% of bacteriostatic effect at MIC of 4 µg/ml. Doses of 20 and 30 mg/Kg IM showed 100% eradication for MIC up to 1 µg/mL and 0% for MIC above. The bacteriostatic effect was maintained at 100% for a MIC of 4 µg/mL at both doses. This study shows the bacteriological eradication effect of florfenicol at doses of 20 and 30 mg/Kg, IV, and IM. Therefore, we recommend an in vivo efficacy study with a dose of 30mg/Kg IM in sheep infected with F. necrophorum with MIC greater than two µg/mL.

Simulación de dosis absorbida en terapia molecular mediante método de Montecarlo utilizando software libre GEANT4: GATE

RESUMEN Fundamento: aún no existe una forma óptima para determinar la dosis absorbida por los tumores; este desconocimiento es la causa de que la dosis final del tratamiento sea impredecible. Por esta causa los pacientes pueden estar recibiendo dosis mayores que las mínimas requeridas para su correcto diagnóstico. Objetivo: crear un código fuente para un proyecto de aplicación del programa GATE en la simulación de la dosis absorbida en radioterapia molecular, por método Montecarlo, para un maniquí de Giap. Métodos: se realizó la simulación por método de Montecarlo a partir de modelar el maniquí de Giap, mediante la plataforma de simulación GATE. Se compararon los resultados obtenidos con la información reflejada en la bibliografía sobre las mejores prácticas estandarizadas. Resultados: se confeccionó un código fuente implementado en GATE para la determinación de la dosis absorbida en radioterapia molecular. Se obtuvo distribución no uniforme de dosis en un medio de actividad uniforme y un 2 % de incertidumbre aproximado (en buena correspondencia con los valores reportados en la literatura), los resultados permiten afirmar que la simulación de dosis por medio de la plataforma GATE es confiable, de poco gasto computacional y altamente recomendable. Conclusiones: es recomendable utilizar la plataforma GATE para la simulación del cálculo de la dosis absorbida por ser rápida, de bajo costo computacional y confiable.

ABSTRACT Background: there is still no optimal way to determine the dose absorbed by tumors; this lack of knowledge is the reason why the final dose of treatment is unpredictable. For this reason, patients may be receiving doses greater than the minimum required for their correct diagnosis. Objective: to create a source code for an application project of the GATE program in the simulation of absorbed dose in molecular radiotherapy, by Monte Carlo method, for a Giap phantom. Methods: the simulation was carried out by the Montecarlo method from modeling the Giap phantom, using the GATE simulation platform. The results obtained were compared with the information reflected in the bibliography on standardized best practices. Results: a source code implemented in GATE was prepared for the determination of the absorbed dose in molecular radiotherapy. Non-uniform distribution of doses was obtained in a medium with uniform activity and an approximate 2% uncertainty (in correspondence with the values reported in the literature), the results allow to affirm that the dose simulation through the GATE platform is reliable, of little computational expense and highly recommended. Conclusions: it is advisable to use the GATE platform for the simulation of the calculation of the absorbed dose because it is fast, of low computational cost and reliable.

Ferramenta in silico para desenvolvimento de métodos cromatográficos - aplicação em misturas de filtros solares / In silico tool for development of chromatographic methods - application in mixtures of sunscreensPalavras-chave em inglês

Planejamento de Experimentos (DoE) permite obter e explorar conhecimentos sobre inúmeros sistemas, facilitando a coleta de informações com reduzido número de experimentos. No entanto, DoE é restrito ao delineamento do desenho experimental. Para superar essa limitação e permitir uma previsão precisa dos tempos de retenção para uma seleção de filtros UV orgânicos sob diversas condições, usamos a Relação Quantitativa entre Estrutura e Retenção combinada com o método de Monte Carlo para desenvolver uma plataforma in silico capaz de prever o perfil cromatográfico de filtros UV orgânicos. Sete analitos foram usados para estabelecer o modelo de predição: benzofenona-3, avobenzona, ethilhexil triazona, octil dimetil PABA, metoxicinamato de octila, tinosorb® S e octocrileno. Os valores residuais obtidos no modelo de análise de regressão múltipla mostraram distribuição normal, homocedasticidade e independência. Os coeficientes de determinação (R2) e predição (R2 pred) foram de 99,82% e 99,71%, respectivamente. A plataforma in silico apresentou grande potencial para predição do perfil cromatográfico de filtros UV orgânicos, da coeluição de analitos, de seus parâmetros cromatográficos, além de permitir, sem experimentação, uma visão geral do comportamento de retenção de compostos sob diversas condições cromatográficas

Design of Experiments (DoE) allows obtaining and explorer knowledge about innumerous systems, facilitating the information collection with reduced number of experiments. However, DoE is restricted to the limited range which experimental design was delineated. In order to overcome this limitation and enable accurate prediction of retention times for a selection of organic UV filters under various conditions, we used the Quantitative Structure-Retention Relationships tool combined with Monte Carlo method to develop an in silico platform capable of predicting chromatographic profile of organic UV filters. Seven analytes were used to established to prediction model: benzophenone-3, butyl methoxydibenzoilmethane, ethylhexyl triazone, ethylhexyl dimetyl PABA, ethylhexyl methoxycinnamate, bisethylhexyloxyphenol methoxyphenyl triazine and octocrylene. Residual values obtained from multiple regression analysis model showed normal distribution, homoscedasticity, and independence. Determination (R2) and prediction (R2 pred) coefficients were found to be 99,82% and 99,71%, respectively. In silico platform presented great potential for predicting chromatographic profile of organic UV filters, analytes coelution, chromatographic parameters and allowing, without experimentation, an overview of retention behavior of compounds under various chromatographic conditions

Simulation of detection efficiency of a portable NaI(Tl) γ spectrometer for monitoring 131I in the thyroid / 中华放射医学与防护杂志

Objective:To simulate the effects of different thyroid-neck phantoms and monitoring positions on the detection efficiency of portable γ spectrometer, and to provide guidance for more accurate on-site measurement of 131I activity in the human thyroid. Methods:Based on the models of 4 typical thyroid-neck phantoms and a 3-inch NaI (TI) γ spectrometer used for the measurement of 131I in the thyroid and combined with the possible field monitoring scenarios, the Monte Carlo method was used to simulate and calculate the detection efficiency of the spectrometer under different conditions of monitoring distance, thyroid depth and thyroid volume. Results:The detection efficiency decreased significantly with the increase in the distance between the detector and the neck surface. The efficiency close to the neck surface was about 15 times that at 15 cm away from the neck surface. The detection efficiency decreased significantly with the increase in thyroid depth. When it was measured at the surface of the neck, the detection efficiency of thyroid at depth of 2 mm was about 3.6 times that of 30 mm. The detection efficiency decreases with the increase in thyroid volume. When it was measured at the neck surface, the detection efficiency of thyroid with 1 ml volume was 1.71 times that with 30 ml. The detection efficiency decreased with the center-point offset of the detector, especially at the neck surface, an offset of 2 cm would reduce the detection efficiency by about 15%.Conclusions:Not only the measurement distance used in calibration, but also the information of the depth and volume of thyroid in the neck-thyroid phantom, is important to know in advance for an accurate measurement of 131I activity in thyroid by using a portable gamma spectrometer.

Preliminary study on Monte Carlo-based simulation and verification of spot scanning carbon ion beam model / 中华放射医学与防护杂志

Objective:To develop a spot scanning carbon ion beam model based on Monte Carlo code FLUKA and verify the accuracy of physical dose.Methods:A geometric model of the treatment nozzle was established in FLUKA. Various parameters such as monoenergy nominal energy, Gaussian energy spectrum distribution, initial spot size, and beam angular distribution in the model were adjusted to match the reference data of integral depth dose (IDD) and in-air spot size measuremed experimentally. Carbon ion beam plans were generated by using the treatment planning system (TPS). The difference in output dose distribution between FLUKA and TPS was compared by the gamma analysis.Results:The differences in Bragg peak width, beam range, and distal falloff width extracted from the IDD curve between the FLUKA model and measured vaues were less than 0.1 mm, with the maximum difference in spot sizes of 0.17 mm. Under the criterion of 2 mm/2% in all the simulations, 2D- and 3D-γ pass rates were all above 95%.Conclusions:An accurate spot scanning carbon beam model was developed based on the Monte Carlo code FLUKA. It has the potential to be used for not only the verification of clinical treatment plans, but also the development of new ion beam therapy equipment and the calculation of biologically effective dose.