Simulation-based Study Research Articles

Model-Based Bioequivalence Analysis to Assess and Predict the Relative Bioavailability of Valproic Acid Formulations.

Model-based bioequivalence (MBBE) encompasses the use of nonlinear mixed effect models supporting the estimation of pharmacokinetic endpoints to assess the relative bioavailability between multi-source drug products. This application emerges as a valuable alternative to the standard non-compartmental analysis (NCA) in bioequivalence (BE) studies in which dense sampling is not possible. In this work, we aimed to assess the application of MBBE compared to traditional methods in evaluating the relative bioavailability of two formulations with different drug release properties. Additionally, we sought to predict the performance of a modified-release formulation in a multiple-dose scenario, leveraging data from a single-dose study. MBBE analysis was implemented to estimate the BE endpoints (90%CI for the Test/Reference geometric mean ratio, T/R GMR) in area under the concentration-time curve (AUC) and maximum concentration (Cmax) using data from a single-dose, 2-period, 2-sequence BE study performed in 14 healthy subjects between a locally developed valproic acid extended-release formulation (Test) and the brand-name delayed-release formulation (Reference). Results were compared with the standard approach, revealing that MBBE analysis achieved higher discrimination between formulations for Cmax, addressing limitations of the experimental sampling design and highlighting an advantage for this model-based analysis even when rich data are available. Additionally, the bioequivalence outcome under the multiple-dose scenario was predicted through a simulation-based study for both total and unbound valproic acid concentrations, considering the impact of valproic acid saturable binding on BE conclusions. The MBBE analysis was superior to the NCA approach in detecting product-related differences, overcoming limitations in the study experimental design. Predictions for the multiple-dose scenario preclude that the extended-release properties of the Test formulation would persist at steady state, resulting in lower peak-to-trough fluctuation and bioequivalent performance in terms of the extent of drug absorption. Overall, these results should discourage unnecessary experimentation in healthy subjects.

A Simulation-Based Study on the Impact of Parametric Design on Outdoor Thermal Comfort and Urban Overheating

Under the current energy crisis and climate change, sustainable urban planning and building design are a priority to achieve a net-zero future, as energy use in buildings for thermal comfort is one of the major carbon emission contributors. To adapt to a rapidly growing and stringent urban environment, where buildings are causing more emissions due to more frequent and severe extreme hot weather events, the parametric design approach has great potential and flexibility in providing a sustainable solution by simulating different design scenarios. This study aims to analyse urban geometry and identify the impact of various built environment scenarios on outdoor thermal comfort under certain climates. The Grasshopper program was used along with the Ladybugs plug-in to provide visualised outcomes of outdoor thermal comfort, with simulation models on Rhinoceros 3D Version 7 SR37 (7.37.24107.1500). Comparing the thermal comfort performance of different design scenarios, based on building height, orientation and urban geometry, helps to identify which factors are more impactful on building design. This study demonstrates the workflow of parametric design in analysing the microclimate pattern and outdoor thermal comfort performance of the existing built environment in Melbourne, Australia, to provide an insight for stakeholders and builders to inform better decision-making in urban planning and building design in order to achieve a zero-emission future.

Assessment of University Parking Management System: A Simulation-Based Study

Assessment of University Parking Management System: A Simulation-Based Study

A Model for Occupational Pensions Privately Administered for Police and Military Personnel

Abstract In the context of legislation introduced in Romania through Law 1 of 2020 regarding occupational pensions, this paper presents an evaluation of occupational pension system for police and military personnel and takes into consideration privately administered funds that would complement the current system. The paper evaluates the impact of the complementary occupational pension system, focusing on its dual role as both a fiscal instrument for internal financing within Romania and a mechanism for enhancing social and economic security for retired police and military staff. The occupational pension system can diversify funding sources, potentially easing the national public debt burden, while offering a sustainable and adequate retirement income for service members. Furthermore, the analysis extends to the occupational pension system's efficacy in fostering workforce stability, particularly post-eligibility for military state pensions. The study addresses the system's potential influence on staff motivation and retention, underpinning its role in maintaining a robust and committed service workforce. This simulation-based study leverages international models and legislative frameworks to corroborate these benefits, providing a nuanced understanding of the occupational pension system’s role in the broader context of public service pensions.

Monolithic all-perovskite tandem solar cells: advancing sustainable energy options

This paper discusses the results of a simulation-based study on lead-free perovskite tandem devices. Wide bandgap (1.8 eV) perovskite materials Cs2AgBi0.75Sb0.25Br6 as the top cell and narrow bandgap (1.3 eV) perovskite materials CsSnI3 as the bottom cell make up the simulated tandem cell device, respectively. The optimisation process involves individually fine-tuning both cells under standard solar radiation conditions of 100 W/m2. The tandem cells necessitate precise current matching between the two sub-cells. The current matching condition manifests at Jsc of 16 mA cm−2 when the top and bottom cells reach an optimised thickness of 700 nm and 65 nm, respectively. The optimised tandem cell achieves a 24.47% power conversion efficiency (PCE), a high Voc of 1.7278 V, and a high fill factor of 83.72%. Furthermore, tandem solar cells’ temperature dependence is examined in the 300 K to 400 K range, revealing that efficiency decreases with temperature due to a reduction in Jsc (short-circuit current). Notably, the current matching condition is primarily influenced by the top cell, which exhibits less variation than the bottom cell. This study paves the way for developing tandem solar cells made entirely of lead-free perovskites and presents a new approach for the experimental realisation of high-power conversion efficiency.

On the role of surface morphology in impacting-freezing dynamics of supercooled droplets

A thorough understanding of droplet impact and freezing is vital in preventing ice accretion on many outdoor devices. This simulation-based study investigated the effect of surface morphology on the impacting-freezing process of a supercooled droplet. Also, the variations of Weber number and supercooling temperature were studied numerically. The droplet impact and freezing process were simulated with the volume of fluid method and freezing model. A more accurate simulation was achieved by modeling the supercooled droplet and the dynamic contact angle. At the given ranges of the input parameters, the main factors that guaranteed droplet rebounding after collision were determined. The supercooling temperature and the groove width should be above 266 K and less than 0.21 mm, respectively. The droplet should also maintain its cohesion and integrity during impact. Creating grooves on a surface is novel and paves a new way to understand the impact and solidification of water droplets in supercooled conditions.

Comparing Leadership Skills of Senior Emergency Medicine Residents in 3-Year Versus 4-Year Programs During Simulated Pediatric Resuscitation: A Pilot Study.

The majority of pediatric patients in the United States (US) are evaluated and treated at general emergency departments. It is possible that discrepancies in length of emergency medicine (EM) residency training may allow for variable exposure to pediatric patients, critical resuscitations, and didactic events. The goal of this pilot study was to compare leadership skills of graduating EM residents from 3- to 4-year programs during simulated pediatric resuscitations using a previously validated leadership assessment tool, the Concise Assessment of Leader Management (CALM). This was a prospective, multicenter, simulation-based cohort pilot study that included graduating 3 rd - and 4 th -year EM resident physicians from 6 EM residency programs. We measured leadership performance across 3 simulated pediatric resuscitations (sepsis, seizure, cardiac arrest) using the CALM tool and compared leadership scores between the 3 rd - and 4 th -year resident cohorts. We also correlated leadership to self-efficacy scores. Data was analyzed for 47 participating residents (24 3 rd -year residents and 23 4 th -year residents). Out of a total possible CALM score of 66, residents from 3-year programs scored 45.2 [SD ± 5.2], 46.8 [SD ± 5.0], and 46.6 [SD ± 4.7], whereas residents from 4-year programs scored 45.5 [SD ± 5.2], 46.4 [SD ± 5.0], and 48.2 [SD ± 4.3] during the sepsis, seizure, and cardiac arrest cases, respectively. The mean leadership score across all 3 cases for the 3-year cohort was 46.2 [SD ± 4.8] versus 46.7 [SD ± 4.5] ( P = 0.715) for the 4-year cohort. These data show feasibility for a larger cohort project and, while not statistically significant, suggest no difference in leadership skills between 3 rd - and 4 th -year EM residents in our study cohort. This pilot study provides the basis of future work that will assess a larger multicenter cohort with the hope to obtain a more generalizable dataset.

Clinical Triggers and Vital Signs Influencing Crisis Acknowledgment and Calls for Help by Anesthesiologists: A Simulation-Based Observational Study

(J Clin Anesth. 2023;90:111235 |https://doi.org/10.1016/j.jclinane.2023.111235) Swiftly mobilizing resources in perioperative emergencies is crucial for patient survival, with anesthesiologists typically bearing this responsibility. Recognizing the urgency, the call for help is emphasized through formalized “stat” calls. However, the timing of seeking assistance remains subjective, posing a challenge. While empirical evidence highlights blood pressure thresholds indicative of harm, ambiguity surrounds terms like “early” in crisis management. An assumption that anesthesiologists must possess all answers hinders timely collaboration, impacting patient care. Factors affecting crisis acknowledgment, especially in simulated settings, were explored among MOCA course participants. Acknowledgment, a pivotal step in emergency response, was scrutinized alongside potential differences between active participants and observers. This investigation seeks to expose vulnerabilities in ACRM implementation, guiding future studies on crisis management in perioperative settings.

Model misspecification, measurement error, and apparent supralinearity in the concentration-response relationship between PM2.5 and mortality.

A growing number of studies have produced results that suggest the shape of the concentration-response (C-R) relationship between PM2.5 exposure and mortality is "supralinear" such that incremental risk is higher at the lowest exposure levels than at the highest exposure levels. If the C-R function is in fact supralinear, then there may be significant health benefits associated with reductions in PM2.5 below the current US National Ambient Air Quality Standards (NAAQS), as each incremental tightening of the PM2.5 NAAQS would be expected to produce ever-greater reductions in mortality risk. In this paper we undertake a series of tests with simulated cohort data to examine whether there are alternative explanations for apparent supralinearity in PM2.5 C-R functions. Our results show that a linear C-R function for PM2.5 can falsely appear to be supralinear in a statistical estimation process for a variety of reasons, such as spatial variation in the composition of total PM2.5 mass, the presence of confounders that are correlated with PM2.5 exposure, and some types of measurement error in estimates of PM2.5 exposure. To the best of our knowledge, this is the first simulation-based study to examine alternative explanations for apparent supralinearity in C-R functions.

Smartphone Use in the Management of Neurological Emergencies: A Simulation-Based Study.

Smartphone use in medicine is nearly universal despite a dearth of research assessing utility in clinical performance. We sought to identify and define smartphone use during simulated neuroemergencies. In this retrospective review of a prospective observational single-center simulation-based study, participants ranging from subinterns to attending physicians and stratified by training level (novice, intermediate, and advanced) managed a variety of neurological emergencies. The primary outcome was frequency and purpose of smartphone use. Secondary outcomes included success rate of smartphone use and performance (measured by completion of critical tasks) of participants who used smartphones versus those who did not. In subgroup analyses we compared outcomes across participants by level of training using t-tests and χ2 statistics. One hundred and three participants completed 245 simulation scenarios. Smartphones were used in 109 (45%) simulations. Of participants using smartphones, 102 participants looked up medication doses, 52 participants looked up management guidelines, 11 participants looked up hospital protocols, and 13 participants used smartphones for assistance with an examination scale. Participants found the correct answer 73% of the time using smartphones. There was an association between participant level and smartphone use with intermediate participants being more likely to use their smartphones than novice or advanced participants, 53% versus 29% and 26%, respectively (p < 0.05). Of the intermediate participants, those who used smartphones did not perform better during the simulation scenario than participants who did not use smartphones (smartphone users' mean score [standard deviation] = 12.3 [2.9] vs. nonsmartphone users' mean score [standard deviation] = 12.9 (2.7), p = 0.85). Participants commonly used smartphones in simulated neuroemergencies but use didn't confer improved clinical performance. Less experienced participants were the most likely to use smartphones and less likely to arrive at correct conclusions, and thus are the most likely to benefit from an evidence-based smartphone application for neuroemergencies.

Heat exposure mitigation in renovated nearly zero-energy dwellings during concurrent heat waves and power outages

As heat waves increase in intensity and duration, the risk of heat exposure in dwellings in countries with mixed humid climates is expected to rise. The impact of heat waves on building performance has been extensively researched. However, building performance during concurrent heat waves and power outages needs further investigation to reduce the dependency on active cooling during critical infrastructure failures. This paper presents a simulation-based study of heat exposure risks for a nearly zero dwelling during a concurrent heat wave and power outage in Brussels, Belgium using weather data from field measurements. Combinations of promising passive design strategies like natural ventilation, cool roof, and solar shading were evaluated along key performance indicators like indoor overheating degree, standard effective temperature, exceedance hours, and heat index. The building performance results showed that existing building-level passive cooling renovation strategies like natural ventilation alone would not be sufficient to mitigate heat exposure with an indoor overheating degree of 0.59 °C. Therefore, they will require additional passive measures like solar shading using window louvres to mitigate heat exposure risks and lower indoor overheating to 0.19 °C. The findings provide unique insights that inform building renovation practices, setting the stage for future research on the topic.

Brood indicators are an early warning signal of honey bee colony loss-a simulation-based study.

Honey bees (Apis mellifera) are exposed to multiple stressors such as pesticides, lack of forage, and diseases. It is therefore a long-standing aim to develop robust and meaningful indicators of bee vitality to assist beekeepers While established indicators often focus on expected colony winter mortality based on adult bee abundance and honey reserves at the beginning of the winter, it would be useful to have indicators that allow detection of stress effects earlier in the year to allow for adaptive management. We used the established honey bee simulation model BEEHAVE to explore the potential of different indicators such as population size, number of capped brood cells, flight activity, abundance of Varroa mites, honey stores and a brood-bee ratio. We implemented two types of stressors in our simulations: 1) parasite pressure, i.e. sub-optimal Varroa treatment by the beekeeper (hereafter referred as Biotic stress) and 2) temporal forage gaps in spring and autumn (hereafter referred as Environmental stress). Neither stressor type could be detected by bee abundance or honey reserves at the end of the first year. However, all response variables used in this study did reveal early warning signals during the course of the year. The most reliable and useful measures seem to be related to brood and the abundance of Varroa mites at the end of the year. However, while in the model we have full access to time series of variables from stressed and unstressed colonies, knowledge of these variables in the field is challenging. We discuss how our findings can nevertheless be used to develop practical early warning indicators. As a next step in the interactive development of such indicators we suggest empirical studies on the importance of the number of capped brood cells at certain times of the year on bee population vitality.

The impact of video consultation on interprofessional collaboration and professional roles: a simulation-based study in prehospital stroke chain of care

ABSTRACT Healthcare is often conducted by interprofessional teams. Research has shown that diverse groups with their own terminology and culture greatly influence collaboration and patient safety. Previous studies have focused on interhospital teams, and very little attention has been paid to team collaboration between intrahospital and prehospital care. Addressing this gap, the current study simulated a common and time-critical event for ambulance nurses (AN) that also required contact with a stroke specialist in a hospital. Today such consultations are usually conducted over the phone, this simulation added a video stream from the ambulance to the neurologist on call. The aim of this study was to explore interprofessional collaboration between AN’s and neurologists when introducing video-support in the prehospital stroke chain of care. The study took place in Western Sweden. The simulated sessions were video recorded, and the participants were interviewed after the simulation. The results indicate that video has a significant impact on collaboration and can help to facilitate better understanding among different professional groups. The participants found the video to be a valuable complement to verbal information. The result also showed challenges in the form of a loss of patient focused care. Both ANs and neurologists saw the video as benefiting patient safety.

Response of sediment microbial communities to the flow effect of the triangular artificial reef: A simulation-based experimental study

Artificial reefs (ARs), as an important tool for habitat restoration, play significant impacts on benthic microbial ecosystems. This study utilized 16S rRNA gene sequencing technology and computational fluid dynamics (CFD) flow simulation to investigate the effects of flow field distribution around ARs on microbial community structure. The results revealed distinct regional distribution patterns of microbial communities affected by different hydrodynamic conditions. Flow velocity and flow regime of water in sediment-water interface shaped the microbial community structure. The diversity and richness in R–HF were significantly decreased compared to other five regions (p < 0.05). At the phyla and OUT levels, most abundant taxa (1>%) showed an enrichment trend in R–HB. However, more than half of differentially abundant taxa were enriched in R–HB, which was significantly correlated with organic matter (OM). Bugbase phenotypic predictions indicated a low abundance of the anaerobic phenotype in R–HF and a high abundance of the biofilm-forming phenotype in R–HB.

Defining management strategies for acute severe ulcerative colitis using predictive models: a simulation-modeling study.

Robust management algorithms are required to reduce the residual risk of colectomy in acute severe ulcerative colitis (ASUC) refractory to standard infliximab salvage therapy. The aim of this study was to evaluate the performance and benefits of alternative ASUC management strategies using simulated prediction models of varying accuracy. This was a simulation-based modeling study using a hypothetical cohort of 5,000 steroid-refractory ASUC patients receiving standard infliximab induction. Simulated predictive models were used to risk-stratify patients and escalate treatment in patients at high risk of failing standard infliximab induction. The main outcome of interest was colectomy by 3 months. The 3-month colectomy rate in the base scenario where all 5,000 patients received standard infliximab induction was 23%. The best-performing management strategy assigned high-risk patients to sequential Janus kinase inhibitor inhibition and mediumrisk patients to accelerated infliximab induction. Using a 90% area under the curve (AUC) prediction model and optimistic treatment efficacy assumptions, this strategy reduced the 3-month colectomy rate to 8% (65% residual risk reduction). Using an 80% AUC prediction model with only modest treatment efficacy assumptions, the 3-month colectomy rate was reduced to 15% (35% residual risk reduction). Overall management strategy efficacy was highly dependent on predictive model accuracy and underlying treatment efficacy assumptions. This is the first study to simulate predictive model-based management strategies in steroid-refractory ASUC and evaluate their effect on short-term colectomy rates. Future studies on predictive model development should incorporate simulation studies to better understand their expected benefit.

Reflecting on Reflection in Clinical Social Work: Unsettling a Key Social Work Strategy

Abstract This study calls into question some of assumptions within social work education and practice regarding the transformational potential of reflection-on-practice. Participants (n = 34) in this simulation-based study each engaged in two clinically focused simulations, each followed by an interview which included observing segments of their video-recorded simulations. The objectives of this study are to make some sense of the misalignments between participants’ post-simulation reflections of their practice behaviours, and the practice behaviours observed by the research team, and later by participants themselves. Findings illustrate that: (i) how clients and the session are understood in the moment can be different than how they are understood post-client engagement; (ii) reflections of practice behaviours can be tied to how individuals want to be, which are not necessarily aligned with how they are in the moment; and (iii) reflections are intertwined with awareness of oneself. These results identify some of the limitations of individualised reflective activities, and demonstrate the powerful potential of collective reflection on recordings of simulations to challenge memory distortions, retrospective biases and to promote greater accountability to ourselves as social workers, and to those we work with.

Evaluation of the detectability of flaws in a two layer structure: A simulation-based PoD study incorporating correlated variables

Evaluation of the detectability of flaws in a two layer structure: A simulation-based PoD study incorporating correlated variables

Ion implantation induced p-type conductivity in FeS2 thin film

In pursuing sustainable energy solutions, thin-film solar cells based on the Copper zinc tin sulfide (CZTS) absorber material have garnered significant attention due to their earth-abundant and non-toxic composition. However, the modest efficiency demonstrated by CZTS solar cells has prompted researchers to investigate novel approaches to improve their performance. An area of potential advancement entails the integration of appropriate hole transport layers (HTLs). In this simulation-based study, we focused on FeS2 as a highly promising candidate for use as an HTL in CZTS-based solar cells. FeS2, traditionally considered n-type, was tailored to achieve p-type conductivity through the negative ion implantation (O, P, and As) process. 40 keV ion beam was utilized, with three doses (105, 1010, 1015 cm−2) applied for each ion beam. We demonstrate successful p-type doping of FeS2 with a hole concentration of ∼1020 cm−3 in case of 1015 cm−2 dose, paving the way for its integration as an effective HTL within the CZTS solar cell structure.

Studying Modern Formula 1 Front Wing at Medium Cornering Speeds

A simulation-based study of three different types of front wing designs used in modern Formula 1 cars was done. The study mainly focuses on the aerodynamic forces that a Formula One car generates mainly the Downforce, the Drag force, &amp; the Lateral force at low cornering speeds. These forces were studied in detail &amp; taking a closer look at how they migrate during the dynamic conditions the car is thrown at various Side Slip (Yaw) Angles, these results were compared with the wing Scuderia Ferrari used in the 1998 formula 1 championship to better understand the inherent problems faced in those previous designs. A brief study of the flow field &amp; flow lines was conducted along with the vortex generation for all three wings. Vortex formation and management is a prominent part of research being carried out for a formula 1 car, so a brief study on the phenomenon of vortex generation &amp; Y250 vortex formation was also carried out. The studies were carried out over typical medium-speed corners where the speed ranges between 150-220 KM/Hr. A study on the effect of the flow field of the top element on the lower element was carried out where the 5th element was removed from each of the three wings &amp; the effect on the downforce &amp; drag value was analysed along with the pressure field.&#x0D; Keywords: Modern formula 1, Front wing designs, Cornering speeds, aerodynamic forces, Side Slip (Yaw) Angles, Centre of pressure (CoP), Lateral force, CFD, Downforce

Emergency airway management in the prone position: an observational mannequin-based simulation study

IntroductionAccidental extubation during prone position can be a life-threatening emergency requiring rapid establishment of the airway. However, there is limited evidence of the best airway rescue method for this potentially catastrophic emergency. The aim of this study was to determine the most effective method to recover the airway in case of accidental extubation during prone positioning by comparing three techniques (supraglottic airway, video laryngoscopy, and fiber-optic bronchoscopy) in a simulated environment.MethodsEleven anesthesiologists and 12 anesthesia fellows performed the simulated airway management using 3 different techniques on a mannequin positioned prone in head pins. Time required for definitive airway management and the success rates were measured.ResultsThe success rates of airway rescue were 100% with the supraglottic airway device (SAD), 69.6% with the video laryngoscope (CMAC), and 91.3% with the FOB. The mean (SD) time to insertion was 18.1 (4.8) s for the supraglottic airway, 78.3 (32.0) s for the CMAC, and 57.3 (24.6) s for the FOB. There were significant differences in the time required for definitive airway management between the SAD and FOB (t = 5.79, p < 0.001, 95% CI = 25.92–52.38), the SAD and CMAC (t = 8.90, p < 0.001, 95% CI = 46.93–73.40), and the FOB and CMAC (t = 3.11, p = 0.003, 95% CI = 7.78–34.25).ConclusionThe results of this simulation-based study suggest that the SAD I-gel is the best technique to manage accidental extubation during prone position by establishing a temporary airway with excellent success rate and shorter procedure time. When comparing techniques for securing a definitive airway, the FOB was more successful than the CMAC.