Impact of coking plant to heavy metal characteristics in groundwater of surrounding areas: Spatial distribution, source apportionment and risk assessments.

Coking industry is a potential source of heavy metals (HMs) pollution. However, its impacts to the groundwater of surrounding residential areas have not been well understood. This study investigated the pollution characteristics and health risks of HMs in groundwater nearby a typical coking plant. Nine HMs including Fe, Zn, Mo, As, Cu, Ni, Cr, Pb and Cd were analyzed. The average concentration of total HMs was higher in the nearby area (244.27 µg/L) than that of remote area away the coking plant (89.15 µg/L). The spatial distribution of pollution indices including heavy metal pollution index (HPI), Nemerow index (NI) and contamination degree (CD), all demonstrated higher values at the nearby residential areas, suggesting coking activity could significantly impact the HMs distribution characteristics. Four sources of HMs were identified by Positive Matrix Factorization (PMF) model, which indicated coal washing and coking emission were the dominant sources, accounted for 40.4%, and 31.0%, respectively. Oral ingestion was found to be the dominant exposure pathway with higher exposure dose to children than adults. Hazard quotient (HQ) values were below 1.0, suggesting negligible non-carcinogenic health risks, while potential carcinogenic risks were from Pb and Ni with cancer risk (CR) values > 10-6. Monte Carlo simulation matched well with the calculated results with HMs concentrations to be the most sensitive parameters. This study provides insights into understanding how the industrial coking activities can impact the HMs pollution characteristics in groundwater, thus facilitating the implement of HMs regulation in coking industries.

A Monte Carlo study comparing dead-time losses of a gamma camera between tungsten functional paper and lead sheet for dosimetry in targeted radionuclide therapy with Lu-177.

OBJECTIVE: Dead-time loss is reported to be non-negligible for some patients with a high tumor burden in Lu-177 radionuclide therapy, even if the administered activity is 7.4 GBq. Hence, we proposed a simple method to shorten the apparent dead time and reduce dead-time loss using a thin lead sheet in previous work. The collimator surface of the gamma camera was covered with a lead sheet in our proposed method. While allowing the detection of 208-keV gamma photons of Lu-177 that penetrate the sheet, photons with energies lower than 208 keV, which cause dead-time loss, were shielded. In this study, we evaluated the usefulness of tungsten functional paper (TFP) for the proposed method using Monte Carlo simulation. METHODS: The count rates in imaging of Lu-177 administered to patients were simulated with the International Commission on Radiological Protection (ICRP) 110 phantom using the GATE Monte Carlo simulation toolkit. The simulated gamma cameras with a 0.5-mm lead sheet, 1.2-mm TFP, or no filter were positioned closely on the anterior and posterior sides of the phantom. The apparent dead times and dead-time losses at 24 h after administration were calculated for an energy window of 208 keV ± 10%. Moreover, the dead-time losses at 24-120 h were analytically assessed using activity excretion data of Lu-177-DOTATATE. RESULTS: The dead-time loss without a filter was 5% even 120 h after administration in patients with a high tumor burden and slow excretion, while those with a lead sheet and TFP were 0.22 and 0.58 times less than those with no filter, respectively. The count rates with the TFP were 1.3 times higher than those with the lead sheet, and the TFP could maintain primary count rates at 91-94% of those without a filter. CONCLUSIONS: Although the apparent dead time and dead-time loss with the lead sheet were shorter and less than those with TFP, those with TFP were superior to those without a filter. The advantage of TFP over the lead sheet is that the decrease in primary count rates was less.

Optimizing number of Raman spectra using an artificial neural network guided Monte Carlo simulation approach to analyze human cortical bone.

This study presents a novel methodology for optimizing the number of Raman spectra required per sample for human bone compositional analysis. The methodology integrates Artificial Neural Network (ANN) and Monte Carlo Simulation (MCS). We demonstrate the robustness of ANN in enabling prediction of Raman spectroscopy-based bone quality properties even with limited spectral inputs. The ANN algorithms tailored to individual sex and age groups, which enhance the specificity and accuracy of predictions in bone quality properties. In addition, ANN guided MCS systematically explores the variability and uncertainty inherent in different sample sizes and spectral datasets, leading to the identification of an optimal number of spectra per sample for characterizing human bone tissues. The findings suggest that as low as 2 spectra are sufficient for biochemical analysis of bone, with R2 values between real and predicted values of v1/PO4/Amide I and ∼I1670/I1640 ratios, ranging from 0.60 to 0.89. Our results also suggest that up to 8 spectra could be optimal when balancing other factors. This optimized approach streamlines experimental workflows, reduces data and acquisition costs. Additionally, our study highlights the potential for advancing Raman spectroscopy in bone research through the innovative integration of ANN-guided probabilistic modeling techniques. This research could significantly contribute to the broader landscape of bone quality analyses by establishing a precedent for optimizing the number of Raman spectra with sophisticated computational tools. It also sets a novel platform for future optimization studies in Raman spectroscopy applications in biomedical field.

Nanoscale dosimetry for a radioisotope-labeled metal nanoparticle using MCNP6.2 and Geant4.

BACKGROUND: Metal nanoparticles (MNPs) labeled with radioisotopes (RIs) are utilized as radio-enhancers due to their ability to amplify the radiation dose in their immediate vicinity. A thorough understanding of nanoscale dosimetry around MNPs enables their effective application in radiotherapy. However, nanoscale dosimetry around MNPs still requires further investigation. PURPOSE: This study aims to provide insight into the radio-enhancement effects of MNPs by elucidating nanoscale dosimetry surrounding MNPs labeled with Auger-emitting RIs. We particularly focus on distinguishing the respective dose contributions of photons and electrons emitted by Auger-emitting RIs in the context of dose enhancement. METHODS: A 50 nm diameter NP of silver (Ag) core and gold (Au) shell (Ag@Au NP) was assumed to emit mono-energetic electrons and photons (3, 5, 10, 20, and 30 keV), or the energy spectrum corresponding to one of three Auger-emitting RIs (103Pd, 125I, and 131Cs) from the Ag core. Nanoscale radial dose distributions around a single radioactive Ag@Au NP were evaluated in spherical shells of water. Monte Carlo simulations were conducted using single-event and track structure transport methods implemented in MCNP6.2 and Geant4-DNA-Au physics, respectively. To evaluate the extent of radio-enhancement by the Ag@Au NP, two scenarios were considered: Ag@Au NPs (Au shell included) and Ag@water NPs (Au shell replaced by water). RESULTS: The radial doses of 10, 20, and 30 keV electrons estimated by both codes were comparable. However, the radial doses of 3 and 5 keV electrons by MCNP6.2 were much larger near the NP surface than those by Geant4. There was a dose enhancement of a few % to tens % by the Au shell in the region of the NP surface to 10 µm, depending on the electron energy. The radial doses of photons with the Au shell were higher up to their secondary electron ranges than those without the Au shell. The maximum dose enhancement factor of photons occurred at 20 keV and was 63.4 by MCNP6.2 and 50.5 by Geant4. The overall radial doses of electrons were 1-2 orders of magnitude larger than those of photons. As a result, in cases of RIs emitting both electrons and photons, the radial doses up to electron ranges were dominantly governed by electrons. The dose enhancement estimated by both codes for the RIs ranged from a few % except in the immediate vicinity of the NP surface. CONCLUSION: Given the dominant contribution of electrons to radial doses of MNP labeled with Auger-emitting RIs, physical dose enhancement expected by interactions with photons was hindered. Since there are no available RIs emitting exclusively photons, achieving enhanced physical doses within a cell through a combination of MNPs and RIs appears currently unattainable. The radial doses of photons near the NP surface exhibited considerable discrepancies between the codes, primarily attributed to low-energy electrons. The difference may arise from higher cross-sections of Au inelastic scattering in Geant4-DNA-Au compared to MCNP6.2.

Visualization of spatial dose distribution for effective radiation protection education in interventional radiology: obtaining high-accuracy spatial doses.

In recent years, eye lens exposure among radiation workers has become a serious concern in medical X-ray fluoroscopy and interventional radiology (IVR), highlighting the need for radiation protection education and training. This study presents a method that can maintain high accuracy when calculating spatial dose distributions obtained via Monte Carlo simulation and establishes another method to three-dimensionally visualize radiation using the obtained calculation results for contributing to effective radiation-protection education in X-ray fluoroscopy and IVR. The Monte Carlo particle and heavy ion transport code system (PHITS, Ver. 3.24) was used for calculating the spatial dose distribution generated by an angiography device. We determined the peak X-ray tube voltage and half value layer using Raysafe X2 to define the X-ray spectrum from the source and calculated the X-ray spectrum from the measured results using an approximation formula developed by Tucker et al. Further, we performed measurements using the "jungle-gym" method under the same conditions as the Monte Carlo calculations for verifying the accuracy of the latter. An optically stimulated luminescence dosimeter (nanoDot dosimeter) was used as the measuring instrument. In addition, we attempted to visualize radiation using ParaView (version 5.12.0-RC2) using the spatial dose distribution confirmed by the above calculations. A comparison of the measured and Monte Carlo calculated spatial dose distributions revealed that some areas showed large errors (12.3 and 24.2%) between the two values. These errors could be attributed to the scattering and absorption of X-rays caused by the jungle gym method, which led to uncertain measurements, and (2) the angular and energy dependencies of the nanoDot dosimetry. These two causes explain the errors in the actual values, and thus, the Monte Carlo calculations proposed in this study can be considered to have high-quality X-ray spectra and high accuracy. We successfully visualized the three-dimensional spatial dose distribution for direct and scattered X-rays separately using the obtained spatial dose distribution. We established a method to verify the accuracy of Monte Carlo calculations performed through the procedures considered in this study. Various three-dimensional spatial dose distributions were obtained with assured accuracy by applying the Monte Carlo calculation (e.g., changing the irradiation angle and adding a protective plate). Effective radiation-protection education can be realized by combining the present method with highly reliable software to visualize dose distributions.

Stress sensitivity analysis of vuggy porous media based on two-scale fractal theory.

Interparticle pore space and vugs are two different scales of pore space in vuggy porous media. Vuggy porous media widely exists in carbonate reservoirs, and the permeability of this porous media plays an important role in many engineering fields. It has been shown that the change of effective stress has important effects on the permeability of vuggy porous media. In this work, a fractal permeability model for vuggy porous media is developed based on the fractal theory and elastic mechanics. Besides, a Monte Carlo simulation is also implemented to obtain feasible values of permeability. The proposed model can predict the elastic deformation of the fractal vuggy porous media under loading stress, which plays a crucial role in the variations of permeability. The predicted permeability data based on the present fractal model are compared with experimental data, which verifies the validity of the present fractal permeability model for vuggy porous media. The parameter sensitivity analysis indicates that the permeability of stress-sensitivity vuggy porous media is related to the capillary fractal dimension, capillary fractal tortuosity dimension, Young's modulus, and Poisson's ratio.

Monte Carlo Model Validation of 6MV Beam of OMID, the First Iranian Linear Accelerator.

Monte Carlo (MC) techniques are regarded as an accurate method to simulate the dose calculation in radiotherapy for many years. The present paper aims to validate the simulated model of the 6-MV beam of OMID linear accelerator (BEHYAAR Company) by EGSnrc codes system and also investigate the effects of initial electron beam parameters (energy, radial full width at half maximum, and mean angular spread) on dose distributions. For this purpose, the comparison between the calculated and measured percentage depth dose (PDD) and lateral dose profiles was done by gamma index (GI) with 1%-1 mm acceptance criteria. MC model validating was done for 3 cm × 3 cm, 5 cm × 5 cm, 8 cm × 8 cm, 10 cm × 10 cm, and 20 cm × 20 cm field sizes. To study the sensitivity of model to beam parameters, the field size was selected as 10 cm × 10 cm and 30 cm × 30 cm. All lateral dose profiles were obtained at 10 cm. Excellent agreement was achieved with a 99.2% GI passing percentage for PDD curves and at least 93.8% GI for lateral dose profiles for investigated field sizes. Our investigation confirmed that the lateral dose profile severely depends on the considered source parameters in this study. PDD only considerably depends on the initial electron beam energy. Therefore, source parameters should not be specified independently. These results indicate that the current model of OMID 6-MV Linac is well established, and the accuracy of the simulation is high enough to be used in various applications.

Pollution area identification, receptor model-oriented sources and probabilistic health hazards to prioritize control measures for heavy metal management in soil.

Identifying the primary source of heavy metals (HMs) pollution and the key pollutants is crucial for safeguarding eco-health and managing risks in industrial vicinity. For this purpose, this investigation was carried out to investigate the pollution area identification with soil static environmental capacity (QI), receptor model-oriented critical sources, and Monte Carlo simulation (MCS) based probabilistic environmental and human health hazards associated with HMs in agricultural soils of Narayanganj, Bangladesh. The average concentration of Cr, Ni, Cu, Cd, Pb, Co, Zn, and Mn were 98.67, 63.41, 37.39, 1.28, 23.93, 14.48, 125.08, and 467.45 mg/kg, respectively. The geoaccumulation index identified Cd as the dominant metal, indicating heavy to extreme contamination in soils. The QI revealed that over 99% of the areas were polluted for Ni and Cd with less uncertain regions whereas Cr showed a significant portion of areas with uncertain pollution status. The positive matrix factorization (PMF) model identified three major sources: agricultural (29%), vehicular emissions (25%), and industrial (46%). The probabilistic assessment of health hazards indicated that both carcinogenic and non-carcinogenic risks for adult male, adult female, and children were deemed unacceptable. Moreover, children faced a higher health hazard compared to adults. For adult male, adult female, and children, industrial operations contributed 48.4%, 42.7%, and 71.2% of the carcinogenic risks, respectively and these risks were associated with Ni and Cr as the main pollutants of concern. The study emphasizes valuable scientific insights for environmental managers to tackle soil pollution from HMs by effectively managing anthropogenic sources. It could aid in devising strategies for environmental remediation engineering and refining industry standards.

Design of a compact and portable space neutron spectrometer based on Monte Carlo.

With the rapid development of space exploration, the detection of space neutron radiation is becoming increasingly important. The currently widely used Bonner sphere spectrometer have drawbacks such as large size and weight, as well as low fault tolerance, when detecting space neutron spectra. This paper describes in detail a new type of space neutron spectrometer (SNS), which has two different specifications to adapt to the directional and non-directional neutron field environment, and can measure the directional neutron energy spectrum. For the directed neutron field, SNS integrates 12 3He thermal neutron counters (diameter 3 cm: 3, diameter 4 cm: 6, diameter 5 cm: 3) and uses cylindrical polyethylene as a moderator. For non-directed neutron fields, SNS integrates 9 3He thermal neutron counters (diameter 3 cm: 4, diameter 4 cm: 3, diameter 5 cm: 2) located in a single structure made of polyethylene, boron-containing polyethylene and gadolinium. The device is capable of providing a strong directional response in the energy range of thermal neutrons up to 20 MeV, with little sensitivity to neutrons coming from directions other than the axis of the cylinder. The Monte Carlo transport code FLUKA was used to determine the final configuration of the instrument, including the arrangement, number, and position of thermal neutron counters. In addition, the response matrix of the instrument was calculated using FLUKA code. This device can replace traditional Bonner sphere spectrometer for measuring space neutrons, and it also provides reference value for downsized and lightweight neutron spectrometers on the ground.

Systematic assessment of source identification and ecological and probabilistic health risks of potentially toxic elements (PTEs) in soils of a typical coal mining area in Guanzhong region.

Mining activities may cause the accumulation of potentially toxic elements (PTEs) in surrounding soils, posing ecological threats and health dangers to the local population. Therefore, a comprehensive assessment using multiple indicators was used to quantify the level of risk in the region. The results showed that the mean values of the nine potentially toxic elements in the study area were lower than the background values only for Cr, and the lowest coefficient of variation was 17.1 % for As, and the spatial distribution characteristics of the elements indicate that they are enriched by different factors. The elements Hg and Cd, which have substantial cumulative features, are the key contributors to ecological risk in the study region, which is overall at moderate risk. APCS-MLR model parses out 4 possible sources: mixed industrial, mining and transportation sources (53.98 %), natural sources (24.56 %), atmospheric deposition sources (12.60 %), and agricultural production sources (8.76 %). The probabilistic health risks show that children are more susceptible to health risks than adults; among children, the safety criteria (HI < 1 and CR < 10-4) were surpassed by 29.29 % of THI and 8.58 % of TCR. According to source-orientated health hazards, the element Ni significantly increases the risk of cancer. Mixed sources from industry, mining, and transportation are important sources of health risks. The results of this research provide some scientific references for the management and decrease of regional ecological and health risks.

Monte Carlo calculated absorbed-dose energy dependence of EBT3 and EBT4 films for 5-200 MeV electrons and 100 keV-15 MeV photons.

PURPOSE: To use Monte Carlo simulations to study the absorbed-dose energy dependence of GAFChromic EBT3 and EBT4 films for 5-200 MeV electron beams and 100 keV-15 MeV photon beams considering two film compositions: a previous EBT3 composition (Bekerat et al.) and the final composition of EBT3/current composition of EBT4 (Palmer et al.). METHODS: A water phantom was simulated with films at 5-50 mm depth in 5 mm intervals. The water phantom was irradiated with flat, monoenergetic 5-200 MeV electron beams and 100 and 150 keV kilovoltage and 1-15 MeV megavoltage photon beams and the dose to the active layer of the films was scored. Simulations were rerun with the films defined as water to compare the absorbed-dose response of film to water, f - 1 ( Q ) = D f i l m D w a t e r $f^{-1}(Q)=\frac{D_{film}}{D_{water}}$ . RESULTS: For electrons, the Bekerat et al. composition had variations in f - 1 ( Q ) $f^{-1}(Q)$ of up to ( 1.9 ± 0.1 ) % $(1.9\,\pm \,0.1)\%$ from 5 to 200 MeV. Similarly, the Palmer et al. composition had differences in f - 1 ( Q ) $f^{-1}(Q)$ up to ( 2.5 ± 0.2 ) % $(2.5 \pm 0.2)\%$ from 5 to 200 MeV. For photons, f - 1 ( Q ) $f^{-1}(Q)$ varied up to ( 2.4 ± 0.3 ) % $(2.4 \pm 0.3)\%$ and ( 4.5 ± 0.7 ) % $(4.5 \pm 0.7)\%$ from 100 keV to 15 MeV for the Bekerat et al. and Palmer et al. compositions, respectively. The depth of films did not appear to significantly affect f - 1 ( Q ) $f^{-1}(Q)$ for photons at any energy and for electrons at energies > $>$  50 MeV. However, for 5 and 10 MeV electrons, decreases of up to ( 10.2 ± 1.1 ) % $(10.2 \pm 1.1)\%$ in f - 1 ( Q ) $f^{-1}(Q)$ were seen due to stacked films and increased beam attenuation in films compared to water. CONCLUSIONS: The up to ( 2.5 ± 0.2 ) % $(2.5 \pm 0.2)\%$ and ( 4.5 ± 0.7 ) % $(4.5 \pm 0.7)\%$ variations in f - 1 ( Q ) $f^{-1}(Q)$ for electrons and photons, respectively, across the energies considered in this study indicate the importance of calibrating films with the energy intended for measurement. Additionally, this work emphasizes potential issues with stacking films to measure depth dose curves, particularly for electron beams with energies ≤ $\le$ 10 MeV.

Design Optimisation of a Flat-Panel, Limited-Angle TOF-PET Scanner: A Simulation Study.

In time-of-flight positron emission tomography (TOF-PET), a coincidence time resolution (CTR) below 100 ps reduces the angular coverage requirements and, thus, the geometric constraints of the scanner design. Among other possibilities, this opens the possibility of using flat-panel PET detectors. Such a design would be more cost-accessible and compact and allow for a higher degree of modularity than a conventional ring scanner. However, achieving adequate CTR is a considerable challenge and requires improvements at every level of detection. Based on recent results in the ongoing development of optimised TOF-PET photodetectors and electronics, we expect that within a few years, a CTR of about 75 ps will be be achievable at the system level. In this work, flat-panel scanners with four panels and various design parameters were simulated, assessed and compared to a reference scanner based on the Siemens Biograph Vision using NEMA NU 2-2018 metrics. Point sources were also simulated, and a method for evaluating spatial resolution that is more appropriate for flat-panel geometry is presented. We also studied the effects of crystal readout strategies, comparing single-crystal and module readout levels. The results demonstrate that with a CTR below 100 ps, a flat-panel scanner can achieve image quality comparable to that of a reference clinical scanner, with considerable savings in scintillator material.

Risk assessment and soil heavy metal contamination near marble processing plants (MPPs) in district Malakand, Pakistan.

Soil heavy metals (HMs) pollution is a growing global concern, mainly in regions with rapid industrial growth. This study assessed the concentrations, potential sources, and health risks of HMs in agricultural soils near marble processing plants in Malakand, Pakistan. A total of 21 soil samples were analyzed for essential and toxic HMs via inductively coupled plasma‒optical emission spectrometry (ICP‒OES), and probabilistic health risks were evaluated via Monte Carlo simulation. The concentrations (mg/kg) of Ca (29,250), P (805.5) and Cd (4.5) exceeded the average shale limits of 22,100, 700, and 3.0 mg/kg, respectively, and indices such as Nemerow's synthetic contamination index (NSCI) and the geoaccumulation index (Igeo) categorized the soil sites as moderately polluted. The potential ecological risk index (PERI) indicated considerable to high ecological risk for As and Cd. The deterministic analysis indicated non-carcinogenic risks for children (HI > 1), whereas the probabilistic analysis suggested no significant risk (HI < 1) for both adults and children. Both methods indicated that the total cancer risk for Cr, Ni, Cd, and As exceeded the USEPA safety limits of 1.0E-06 and 1.0E-04. Sensitivity analysis identified heavy metal concentration, exposure duration, and frequency as key risk factors. The study suggested that HM contamination is mainly anthropogenic, poses a threat to soil and human health, and highlights the need for management strategies and surveillance programs to mitigate these risks.

A Comparison of Green, Delta, and Monte Carlo Methods to Select an Optimal Approach for Calculating the 95% Confidence Interval of the Population-attributable Fraction: Guidance for Epidemiological Research.

Objectives: This study aimed to compare the Delta, Greenland, and Monte Carlo methods for estimating 95% confidence intervals (CIs) of the population-attributable fraction (PAF). The objectives were to identify the optimal method and to determine the influence of primary parameters on PAF calculations. Methods: A dataset was simulated using hypothetical values for primary parameters (population, relative risk [RR], prevalence, and variance of the beta estimator [V(ß Ì‚)]) involved in PAF calculations. Three methods (Delta, Greenland, and Monte Carlo) were used to estimate the 95% CIs of the PAFs. Perturbation analysis was performed to assess the sensitivity of the PAF to changes in these parameters. An R Shiny application, the "GDM-PAF CI Explorer," was developed to facilitate the analysis and visualization of these computations. Results: No significant differences were observed among the 3 methods when both the RR and p-value were low. The Delta method performed well under conditions of low prevalence or minimal RR, while Greenland's method was effective in scenarios with high prevalence. Meanwhile, the Monte Carlo method calculated 95% CIs of PAFs that were stable overall, though it required intensive computational resources. In a novel approach that utilized perturbation for sensitivity analysis, V[ß Ì‚] was identified as the most influential parameter in the estimation of CIs. Conclusions: This study emphasizes the necessity of a careful approach for comparing 95% CI estimation methods for PAFs and selecting the method that best suits the context. It provides practical guidelines to researchers to increase the reliability and accuracy of epidemiological studies.

Geographical analysis of fluoride and nitrate and its probabilistic health risk assessment utilizing Monte Carlo simulation and GIS in potable water in rural areas of Mathura region, Uttar Pradesh, northern India.

Human health is being increasingly exposed to fluoride and nitrate ingestion globally due to anthropogenic alternations in groundwater resources. In the present research work, a hazard quotient (HQ), Monte Carlo simulation (MCS), and geographic information systems (GIS) have been used to estimate the non-carcinogenic health risk of nitrate and fluoride in vulnerable adults, teenagers, and children living in far-flung areas of Uttar Pradesh, Northern India. About 110 samples from some nearby populations were collected and analyzed for nitrates by ion chromatography and fluoride by a fluoride-selective electrode. The results indicated that the concentrations of fluoride and nitrate in the sampling areas ranged from 0.21 to 1.71 mg/L and 0.4-183.54 mg/L, respectively, with mean concentrations of about 1.20 mg/L and 51.52 mg/L for fluoride and nitrate, respectively. The results indicated that 27.27 % of the fluoride samples (27 out of 110) and 45.45 % of the nitrate samples (44 out of 110) were above the standard limits set by WHO. The calculated average HQ values fluoride and Nitrate for children, teenagers and adults were 1.88, 0.98, 0.90 and 3.02, 1.57, 1.45 respectively The 95th percentile HQ values for fluoride were 2.87 for children and 1.03 for adults, while those for nitrate were 4.10 for children and 1.98 for adults. Results of the health risk assessment show that there is a high potential for both non-carcinogenic and cancer risks from fluoride and nitrate through the consumption of groundwater. The Monte Carlo simulation showed the uncertainties and increased risks for children; therefore, one can infer that rural groundwater of the Mathura region, Uttar Pradesh, India, must be treated to make it potable for consumption.

Toward Model-Informed Precision Dosing for Remimazolam: A Population Pharmacokinetic-Pharmacodynamic Analysis.

Remimazolam, widely used for procedural sedation and general anesthesia, is a new ultra short-acting benzodiazepine for intravenous sedation and anesthesia. We aim to characterize the pharmacokinetics/pharmacodynamics (PK/PD) of remimazolam and its metabolite CNS 7054 in healthy Chinese volunteers using population analysis and suggest an optimal dosing regimen for sedation therapy. Data were collected from a single-center, placebo-controlled, randomized, and dose-escalation clinical pharmacology study. Forty-six healthy volunteers received a single infusion dose of remimazolam, while nine healthy subjects received a continuous infusion of remimazolam. A population PK/PD model was established and RxODE and Shiny in R were used to design the remimazolam dosing regimens. A three-compartment model best described the PK of remimazolam and a two-compartment model with one transit compartment was adopted for CNS 7054. The relationship between exposure and the bispectral index was best described using an effect compartment model with an inhibitory sigmoid model. Additionally, a web-based dashboard was developed to provide individualized dosing regimens, complemented by a graphical illustration of the PK/PD profiles of the proposed dosing regimen. The established population PK/PD model characterized the dose-exposure-response relationship of remimazolam well, which could be applied to optimize individual dosing regimens.

Pharmacokinetics of Piperacillin-Tazobactam in Critically Ill Patients with Open Abdomen and Vacuum-Assisted Wound Closure: Dosing Considerations Using Monte Carlo Simulation.

BACKGROUND: Open abdomen with vacuum-assisted wound closure therapy (OA/VAC) is frequently used in critically ill patients although the impact of OA/VAC on antibiotics pharmacokinetics (PK) remains unknown. We thus aimed to characterize the PK of piperacillin-tazobactam (PTZ) in critically ill patients with OA/VAC and assess the optimal dosing regimens based on pharmacodynamics (PD) target attainment. METHODS: Over a 15-month study period, 45 patients with OA/VAC treated with PTZ administered continuously and adapted to 24 h creatinine clearance (CLCR) underwent measurements of free concentrations in their plasma, urine, VAC exudate, and peritoneal fluid. Population PK modeling was performed considering the effect of covariates, and Monte Carlo simulations were employed to determine the probability of target attainment (PTA) for the PK/PD targets (100% fT > 16 mg/L) in the plasma and at the peritoneal site at steady state. RESULTS: Piperacillin concentrations were described using a two-compartment model, with age and total body weight as significant covariates for central volume of distribution (V1) and estimated renal function for clearance (CL). Tazobactam concentrations were described using a two-compartment model with estimated renal function as a significant covariate. The central volume of distributions V1 of piperacillin and tazobactam were 21.2 and 23.2 L, respectively. The VAC-induced peritoneal clearance was negligible compared to renal clearance. Most patients achieved the desirable PK/PD target when using a CLCR-pondered PTZ dosing regimen from 12 g/1.5 g/day to 20 g/2.5 g/day. CONCLUSIONS: Despite a wide inter-individual variability, the influence of OA/VAC on piperacillin and tazobactam PK parameters is not straightforward. The use of a CLCR-pondered PTZ dosing regimen from 12 g/1.5 g/day to 20 g/2.5 g/day is needed to reach a PTA > 85%.

Reliability-Based Design Optimization for Polymer Electrolyte Membrane Fuel Cells: Tackling Dimensional Uncertainties in Manufacturing and Their Effects on Costs of Cathode Gas Diffusion Layer and Bipolar Plates.

Polymer Electrolyte Membrane Fuel Cells (PEMFCs) have emerged as a pivotal technology in the automotive industry, significantly contributing to the reduction of greenhouse gas emissions. However, the high material costs of the gas diffusion layer (GDL) and bipolar plate (BP) create a barrier for large scale commercial application. This study aims to address this challenge by optimizing the material and design of the cathode, GDL and BP. While deterministic design optimization (DDO) methods have been extensively studied, they often fall short when manufacturing uncertainties are introduced. This issue is addressed by introducing reliability-based design optimization (RBDO) to optimize four key PEMFC design variables, i.e., gas diffusion layer thickness, channel depth, channel width and land width. The objective is to maximize cell voltage considering the material cost of the cathode gas diffusion layer and cathode bipolar plate as reliability constraints. The results of the DDO show an increment in cell voltage of 31 mV, with a reliability of around 50% in material cost for both the cathode GDL and cathode BP. In contrast, the RBDO method provides a reliability of 95% for both components. Additionally, under a high level of uncertainty, the RBDO approach reduces the material cost of the cathode GDL by up to 12.25 $/stack, while the material cost for the cathode BP increases by up to 11.18 $/stack Under lower levels of manufacturing uncertainties, the RBDO method predicts a reduction in the material cost of the cathode GDL by up to 4.09 $/stack, with an increase in the material cost for the cathode BP by up to 6.71 $/stack, while maintaining a reliability of 95% for both components. These results demonstrate the effectiveness of the RBDO approach in achieving a reliable design under varying levels of manufacturing uncertainties.

Natural background level, source apportionment and health risk assessment of potentially toxic elements in multi-layer aquifers of arid area in Northwest China.

Groundwater contaminated by potentially toxic elements has become an increasing global concern for human health. Therefore, it is crucial to identify the sources and health risks of potentially toxic elements, especially in arid areas. Despite the necessity, there is a notable research gap concerning the sources and risks of these elements within multi-layer aquifers in such regions. To address this gap, 54 phreatic and 24 confined groundwater samples were collected from an arid area in Northwest China. This study aimed to trace the sources and evaluate the human health risks of potentially toxic elements by natural background level (NBL), positive matrix factorization (PMF) model, and health risk model. Findings revealed exceeding levels of potentially toxic elements existed in phreatic and confined aquifers. Source apportionment and NBL results indicated that mineral dissolution, evaporation, redox reactions, and human activities were the main factors for elevated concentrations of potentially toxic elements. High Fe and Mn concentrations were attributed to reduction environments, while F accumulation resulted from slow runoff, and irrigation from the Yellow River. Due to high F levels, more than one-third of groundwater samples (phreatic: 33.14 %, confined: 56.22 %) posed non-carcinogenic health risks to population groups. Adults displayed higher carcinogenic risks (phreatic: 19.47 %, confined: 34.16 %) than infants (phreatic: 0 %, confined: 0 %) and children (phreatic: 1.26 %, confined: 7.97 %) owing to the toxic elements of Cr. The confined aquifer presented greater health risks than the phreatic aquifer. Consequently, controlling the levels of F and Cr in multi-layered aquifers is key to reducing health risks. These findings provide valuable insights into protecting groundwater from contamination by potentially toxic elements in multi-layered aquifers worldwide.

Precision Dosing of Meropenem in Adults with Normal Renal Function: Insights from a Population Pharmacokinetic and Monte Carlo Simulation Study.

This study aimed to develop a population pharmacokinetic (PK) model for meropenem in healthy adults and explore optimal dosing regimens for patients with normal renal function. PK samples were obtained from 12 healthy participants, which were analyzed using noncompartmental analysis and nonlinear mixed-effect modeling. The PK profiles of meropenem were characterized using a two-compartment model, and serum creatinine level was identified as a significant covariate affecting total clearance. Monte Carlo simulations were conducted using this model to inform dosing recommendations. The target index for meropenem efficacy was defined as the cumulative percentage over 24 h during which free (f) drug concentration exceeded the minimum inhibitory concentration (MIC) under steady state conditions (fT>MIC). These simulations indicated that the current dosage regimen of 1 g for 30 min infusions every 8 h achieved a 90% probability of target attainment (PTA) for 40%fT>MIC when the MIC was <2 mg/L. However, to achieve more stringent therapeutic targets, such as a 90%PTA for 100%fT>MIC or a 90%PTA for 100%fT>4MIC, higher doses administered as 3 h extended infusions or as continuous infusions may be necessary. These results highlight the need for model-informed precision dosing to enhance the efficacy of meropenem therapy across various MIC levels and therapeutic targets.