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Development and application of a population pharmacokinetic model repository for caffeine dose tailoring in preterm infants

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EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY 2024年第9期20卷 923-938页

作者： Dai, Hao-Ran Guo, Hong-Li Hu, Ya-Hui Liu, Yun Lu, Ke-Yu Zhang, Yuan-Yuan Wang, Jie Ding, Xuan-Sheng Jiao, Zheng Cheng, Rui Chen, Feng Nanjing Med Univ Childrens Hosp Pharmaceut Sci Res Ctr Dept Pharm 72 Guangzhou Rd Nanjing 210008 Peoples R China China Pharmaceut Univ Sch Basic Med & Clin Pharm Nanjing Peoples R China Nanjing Med Univ Childrens Hosp Neonatal Intens Care Unit 72 Guangzhou Rd Nanjing Peoples R China Shanghai Jiao Tong Univ Shanghai Chest Hosp Sch Med Dept Pharm 241 Huaihai West Rd Shanghai 200030 Peoples R China

BackgroundConsiderable interindividual variability for the pharmacokinetics of caffeine in preterm infants has been demonstrated, emphasizing the importance of personalized dosing. This study aimed to develop and apply a repository of currently published population pharmacokinetic (PopPK) models of caffeine in preterm infants to facilitate model-informed precision dosing (MIPD).Research design and methodsLiterature search was conducted using PubMed, Embase, Scopus, and Web of Science databases. Relevant publications were screened, and their quality was assessed. PopPK models were reestablished to develop the model repository. Covariate effects were evaluated and the concentration-time profiles were simulated. An online simulation and calculation tool was developed as an *** PopPK models were finally included in the repository. Preterm infants' age and body size, especially the postnatal age and current weight, were identified as the most clinically critical covariates. Simulated blood concentration-time profiles across these models were comparable. Caffeine citrate-dose regimen should be adjusted according to the age and body size of preterm infants. The developed online tool can be used to facilitate clinical *** first developed repository of PopPK models for caffeine in preterm infants has a wide range of potential applications in the MIPD of caffeine.

关键词： Caffeine preterm infants population pharmacokinetics model-informed precision dosing model repository

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Factory optima: a web-based system for composition and analysis of manufacturing service networks based on a reusable model repository

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INTERNATIONAL JOURNAL OF COMPUTER INTEGRATED MANUFACTURING 2019年第3期32卷 206-224页

作者： Brodsky, Alexander Nachawati, Mohamad Omar Krishnamoorthy, Mohan Bernstein, William Z. Menasce, Daniel A. George Mason Univ Dept Comp Sci Fairfax VA 22030 USA NIST Syst Integrat Div Gaithersburg MD 20899 USA

This paper reports on the development of Factory Optima, a web-based system that allows manufacturing process engineers to compose, optimise and perform trade-off analysis of manufacturing and contract service networks based on a reusable repository of performance models. Performance models formally describe process feasibility constraints and metrics of interest, such as cost, throughput and CO2 emissions, as a function of fixed and control parameters, such as equipment and contract properties and settings. The repository contains performance models representing (1) unit manufacturing processes, (2) base contract services and (3) a composite steady-state service network. The proposed framework allows process engineers to hierarchically compose model instances of service networks, which can represent production cells, lines, factory facilities and supply chains, and perform deterministic optimisation based on mathematical programming and Pareto-optimal trade-off analysis. Factory Optima is demonstrated using a case study of a service network for a heat sink product which involves contract vendors and manufacturing activities, including cutting, shearing, Computer Numerical Control (CNC) machining with milling and drilling operations, quality inspection, finishing, and assembly.

关键词： Performance models model repository optimisation analytics decision support service composition

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Fast model repository as Memory for Web Applications 13

Fast Model Repository as Memory for Web Applications

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13th International Baltic Conference on Databases and Information Systems (DB and IS)

作者： Kozlovics, Sergejs Univ Latvia Inst Math & Comp Sci Riga Latvia

ISBN: (纸本)9781614999416;9781614999409

We address the task of migrating standalone model-based applications to the web, where we face the need to synchronize models between the client and the server. Because of synchronization overhead and limited server memory that has to be shared among all connected users, there is the risk that the model storage could become a bottleneck. We propose a model repository that uses an efficient encoding of the model that resembles its Kolmogorov complexity and is suitable for direct sending over the network (with almost no serialization overhead). All traverse and query operations can also be implemented efficiently by introducing just 3 automatic indexes. By utilizing the OS paging mechanism, we are able to hold 10,000 and more repositories on a single server.

关键词： models model repository web applications

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A model repository Description Language - MRDL 15th

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15th International Conference on Software Reuse (ICSR)

作者： Hamid, Brahim Univ Toulosue IRIT 118 Route Narbonne F-31062 Toulouse 9 France

ISBN: (纸本)9783319351223;9783319351216

repository-based development of software systems has gained more attention recently by addressing new challenges such as security and dependability. However, there are still gaps in existing modeling languages and/or formalisms dedicated to define model repositories and the way how to reuse them in the automation of software development. Thus, there is a strong requirement for defining a model repository description language not only as a modeling approach, but also as a suitable instrument to support system and software engineers in the activity of search and retrieval of appropriate models beyond keyword-based search. Moreover, modeling approaches allow using tools for the specification and the exploitation of the designed artifacts (e.g. analysis and evaluation). The goal of this paper is to advance the state of the art in model repository description for software and systems engineering. In particular, we have designed a flexible and extensible modeling language, by means of an OMG style metamodel, to specify model repositories for modeling artifacts, and we have defined an operational architecture for development tools. In particular, we show the feasibility of our own approach by reporting some preliminary prototype providing a model-based repository of security and dependability (S&D) pattern models.

关键词： model repository Metamodel model-driven engineering Software system engineering

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Assessment of the SEMCO model-Based repository Approach for Software System Engineering 7th

Assessment of the SEMCO Model-Based Repository Approach for ...

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7th International Conference on model and Data Engineering (MEDI)

作者： Hamid, Brahim Univ Toulouse IRIT 118 Route Narbonne F-31062 Toulouse 9 France

ISBN: (纸本)9783319668543;9783319668536

We have developed a methodological tool support for software development based on the reuse of dedicated subsystems, that have been pre-engineered to adapt to a specific domain. This paper proposes an empirical evaluation of the proposed approach through its practical application to a use case in the railway domain with strong security and dependability requirements, followed by a description of a survey performed among domain experts to better understand their perceptions regarding our approach. The case study enables us to determine that our approach centered around a model-based repository of patterns leads to a reduction in the number of steps in the engineering process or to their simplification. The survey assists in assessing whether domain experts agree on the benefits of adopting the model-based repository approach in a real industrial context.

关键词： modeling artifact model-based repository model repository Metamodel model-driven engineering Software system engineering

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Developing a Blast Injury modeling Capability: Application of Concepts from the Defense M&S Domain

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JOURNAL OF DEFENSE modelING AND SIMULATION-APPLICATIONS METHODOLOGY TECHNOLOGY-JDMS 2025年第2期22卷 83-103页

作者： Byrne, Ryan Davis, Nichole Gupta, Raj Santago II, Anthony Tolk, Andreas MITRE Corp 7515 Colshire Dr Mclean VA 22102 USA US Army Med Res & Dev Command US Dept Def Blast Injury Res Coordinating Off Ft Detrick MD USA

Increases in computational power have contributed to growing interest in using modeling and simulation (M & S) to better understand and address blast injury for US service members. The development of an M & S capability that can comprehensively simulate human injury, lethality, and impairment due to blast injury threats in the military environment requires a large, coordinated integration of many models and simulations. This contribution describes how various lessons learned from the defense M & S domain were used to support the future development of an envisioned modeling Capability for blast injury by providing simulation functionality for simulation-based experimentation. It first addresses conceptually the interoperability challenges when more than one simulation can be or must be applied and possibly composed for the experiment. This leads to the development of a proposed concept of operations for the application of the modeling Capability and the development of a framework of services needed to allow the identification of an applicable simulation solution, selecting the subset of those simulations, composing them for the experiment, and assessing the results. As a nascent endeavor, anticipated challenges for implementing these concepts are discussed, leveraging lessons learned regarding interoperability, composability, use of services, repositories, and development of simulation compositions to conduct simulation-based experiments.

关键词： Blast injury composability conceptual alignment interoperability model curation model repository

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EvoStore: Towards Scalable Storage of Evolving Learning models 24

EvoStore: Towards Scalable Storage of Evolving Learning Mode...

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33rd International Symposium on High-Performance Parallel and Distributed Computing (HPDC)

作者： Underwood, Robert Madhyastha, Meghana Burns, Randal Nicolae, Bogdan Argonne Nat Lab Lemont IL 60439 USA Johns Hopkins Univ Baltimore MD USA

ISBN: (纸本)9798400704130

Deep Learning (DL) has seen rapid adoption in all domains. Since training DL models is expensive, both in terms of time and resources, application workflows that make use of DL increasingly need to operate with a large number of derived learning models, which are obtained through transfer learning and fine-tuning. At scale, thousands of such derived DL models are accessed concurrently by a large number of processes. In this context, an important question is how to design and develop specialized DL model repositories that remain scalable under concurrent access, while addressing key challenges: how to query the DL model architectures for specific patterns? How to load/store a subset of layers/tensors from a DL model? How to efficiently share unmodified layers/tensors between DL models derived from each other through transfer learning? How to maintain provenance and answer ancestry queries? State of art leaves a gap regarding these challenges. To fill this gap, we introduce EvoStore, a distributed DL model repository with scalable data and metadata support to store and access derived DL models efficiently. Large-scale experiments on hundreds of GPUs show significant benefits over state-of-art with respect to I/O and metadata performance, as well as storage space utilization.

关键词： AI model repository Network Architecture Search Regulartized Evolution Distributed AI for HPC

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A Proposal for a models-meet-Data repository For Digital Twins in Construction Engineering 21

A Proposal for a Models-meet-Data Repository For Digital Twi...

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21st International Conference on Software Architecture (ICSA)

作者： Zech, Philipp Pobitzer, Philipp Froech, Georg Breu, Ruth Univ Innsbruck Dept Comp Sci Tyrol Austria Univ Innsbruck Unit Construct Management & Tunneling Tyrol Austria

ISBN: (纸本)9798350366266;9798350366259

Digital twins enable real-time, model- and databased simulations of physical assets or systems yielding more effective monitoring, analysis, and decision-making for enhanced performance and efficiency. The construction industry is highly interested in utilizing digital twins due to their potential to facilitate collaboration along the building life cycle, optimizing building energy usage, asset life cycle management, and data-driven decision-making to achieve sustainability objectives. Currently, necessary technological solutions that effectively tackle the inherent challenge of federating and integrating models and data that arises in these scenarios are however missing. Expanding upon the achievements of model-based engineering and its technological infrastructure, we propose a model repository for digital twins that tackles the models-meet-data challenge and establishes a technological basis for collaborative workflows. To this end, we carried out an extended requirements elicitation, architectural synthesis, and validation procedures. Preliminary empirical findings using an initial prototype suggest that the repository exhibits the necessary scalability, performance and isolation for collaborative work.

关键词： Digital Twin models-meet-data model repository Digital Twin repository Architecture Analysis

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Multi-objective model transformation chain exploration with MOMoT

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INFORMATION AND SOFTWARE TECHNOLOGY 2024年 174卷

作者： Eisenberg, Martin Sahay, Apurvanand Di Ruscio, Davide Iovino, Ludovico Wimmer, Manuel Pierantonio, Alfonso Johannes Kepler Univ Linz CDL MINT Linz Austria Amrita Vishwa Vidyapeetham Amrita Sch Comp Bengaluru India Univ Aquila Laquila Italy Gran Sasso Sci Inst Laquila Italy

Context: The increasing complexity of modern systems leads to an increasing amount of artifacts that are used along the model-based software and systems development lifecycle. This also includes model transformations, which serve for mapping models between representations, e.g., for verification and validation purposes. Objectives: model repositories manage this variety of artifacts and promote reusability, but should also enable the bundling of compatible artifacts. Therefore, model transformations should be reused and arranged into transformation chains to support more complex transformation scenarios. The resulting transformation should correspond to the user's interest in terms of quality criteria such as model coverage, transformation coverage, and number of transformation steps, thus assembling such chains becomes a multi -objective problem. Methods: A novel multi -objective approach for exploring possible transformation chains residing in model repositories is presented. MOMoT, a model-driven optimization framework, is leveraged to explore the transformation space spanned by the repository. For demonstration, three differently populated repositories are considered. Results: We have extended MOMoT with an exhaustive, multi -objective search that explores the entire model transformation space defined by graph transformation rules, allowing all possible transformation chains to be considered as solution. Accordingly, the optimal solutions were identified in the demonstration cases with negligible computation time. Conclusion: The approach assists modelers when there are multiple chains for transforming an input model to a specified output model to consider. Our evaluation shows that the approach elicits all legitimate transformation chains, thus enabling the modelers to consider trade-offs in view of multiple criteria selection.

关键词： model-driven optimization Transformation chain Multi-objective graph traversal model repository

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Unveiling interactions between intervertebral disc morphologies and mechanical behavior through personalized finite element modeling

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FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY 2024年 12卷 1384599页

作者： Munoz-Moya, Estefano Rasouligandomani, Morteza Ruiz Wills, Carlos Chemorion, Francis Kiptengwer Piella, Gemma Noailly, Jerome Univ Pompeu Fabra Dept Engn BCN MedTech Barcelona Spain InSilicoTrials Technol Dept Informat Technol Trieste Italy

Introduction: Intervertebral Disc (IVD) Degeneration (IDD) is a significant health concern, potentially influenced by mechanotransduction. However, the relationship between the IVD phenotypes and mechanical behavior has not been thoroughly explored in local morphologies where IDD originates. This work unveils the interplays among morphological and mechanical features potentially relevant to IDD through Abaqus UMAT ***: A groundbreaking automated method is introduced to transform a calibrated, structured IVD finite element (FE) model into 169 patient-personalized (PP) models through a mesh morphing process. Our approach accurately replicates the real shapes of the patient's Annulus Fibrosus (AF) and Nucleus Pulposus (NP) while maintaining the same topology for all models. Using segmented magnetic resonance images from the former project MySpine, 169 models with structured hexahedral meshes were created employing the Bayesian Coherent Point Drift++ technique, generating a unique cohort of PP FE models under the Disc4All initiative. Machine learning methods, including Linear Regression, Support Vector Regression, and eXtreme Gradient Boosting Regression, were used to explore correlations between IVD morphology and ***: We achieved PP models with AF and NP similarity scores of 92.06\% and 92.10\% compared to the segmented images. The models maintained good quality and integrity of the mesh. The cartilage endplate (CEP) shape was represented at the IVD-vertebra interfaces, ensuring personalized meshes. Validation of the constitutive model against literature data showed a minor relative error of 5.20%.Discussion: Analysis revealed the influential impact of local morphologies on indirect mechanotransduction responses, highlighting the roles of heights, sagittal areas, and volumes. While the maximum principal stress was influenced by morphologies such as heights, the disc's ellipticity influenced the minimum principal stress. Results suggest th

关键词： patient-specific intervertebral disc morphing algorithm finite element method machine learning model repository patient-personalized morphological analysis

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