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Leeners, B.; Krueger, T.; Geraedts, K.; Tronci, E.; Mancini, T.; Ille, F.; Egli, M.; Roeblitz, S.; Wunder, D.; Saleh, L.; Schippert, C.; Hengartner, M.P. |
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Title |
Cognitive function in association with high estradiol levels resulting from fertility treatment |
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Journal Article |
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Year |
2021 |
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Hormones and Behavior |
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130 |
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104951 |
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Cognition, Estrogen, Estradiol, Fertility treatment, Attention, Cognitive bias |
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The putative association between hormones and cognitive performance is controversial. While there is evidence that estradiol plays a neuroprotective role, hormone treatment has not been shown to improve cognitive performance. Current research is flawed by the evaluation of combined hormonal effects throughout the menstrual cycle or in the menopausal transition. The stimulation phase of a fertility treatment offers a unique model to study the effect of estradiol on cognitive function. This quasi-experimental observational study is based on data from 44 women receiving IVF in Zurich, Switzerland. We assessed visuospatial working memory, attention, cognitive bias, and hormone levels at the beginning and at the end of the stimulation phase of ovarian superstimulation as part of a fertility treatment. In addition to inter-individual differences, we examined intra-individual change over time (within-subject effects). The substantial increases in estradiol levels resulting from fertility treatment did not relate to any considerable change in cognitive functioning. As the tests applied represent a broad variety of cognitive functions on different levels of complexity and with various brain regions involved, we can conclude that estradiol does not show a significant short-term effect on cognitive function. |
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0018-506x |
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MCLab @ davi @ Leeners2021104951 |
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185 |
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Sinisi, S.; Alimguzhin, V.; Mancini, T.; Tronci, E. |
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Reconciling interoperability with efficient Verification and Validation within open source simulation environments |
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Journal Article |
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2021 |
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Simulation Modelling Practice and Theory |
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102277 |
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Simulation, Verification and Validation, Interoperability, FMI/FMU, Model Exchange, Cyber-Physical Systems |
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A Cyber-Physical System (CPS) comprises physical as well as software subsystems. Simulation-based approaches are typically used to support design and Verification and Validation (V&V) of CPSs in several domains such as: aerospace, defence, automotive, smart grid and healthcare. Accordingly, many simulation-based tools are available to support CPS design. This, on one side, enables designers to choose the toolchain that best suits their needs, on the other side poses huge interoperability challenges when one needs to simulate CPSs whose subsystems have been designed and modelled using different toolchains. To overcome such an interoperability problem, in 2010 the Functional Mock-up Interface (FMI) has been proposed as an open standard to support both Model Exchange (ME) and Co-Simulation (CS) of simulation models created with different toolchains. FMI has been adopted by several modelling and simulation environments. Models adhering to such a standard are called Functional Mock-up Units (FMUs). Indeed FMUs play an essential role in defining complex CPSs through, e.g., the System Structure and Parametrization (SSP) standard. Simulation-based V&V of CPSs typically requires exploring different simulation scenarios (i.e., exogenous input sequences to the CPS under design). Many such scenarios have a shared prefix. Accordingly, to avoid simulating many times such shared prefixes, the simulator state at the end of a shared prefix is saved and then restored and used as a start state for the simulation of the next scenario. In this context, an important FMI feature is the capability to save and restore the internal FMU state on demand. This is crucial to increase efficiency of simulation-based V&V. Unfortunately, the implementation of this feature is not mandatory and it is available only within some commercial software. As a result, the interoperability enabled by the FMI standard cannot be fully exploited for V&V when using open-source simulation environments. This motivates developing such a feature for open-source CPS simulation environments. Accordingly, in this paper, we focus on JModelica, an open-source modelling and simulation environment for CPSs based on an open standard modelling language, namely Modelica. We describe how we have endowed JModelica with our open-source implementation of the FMI 2.0 functions needed to save and restore internal states of FMUs for ME. Furthermore, we present experimental results evaluating, through 934 benchmark models, correctness and efficiency of our extended JModelica. Our experimental results show that simulation-based V&V is, on average, 22 times faster with our get/set functionality than without it. |
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MCLab @ davi @ Sinisi2021102277 |
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186 |
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Mancini, T.; Mari, F.; Massini, A.; Melatti, I.; Tronci, E. |
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Title |
On Checking Equivalence of Simulation Scripts |
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2021 |
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Journal of Logical and Algebraic Methods in Programming |
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100640 |
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Formal verification, Simulation based formal verification, Formal Verification of cyber-physical systems, System-level formal verification |
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To support Model Based Design of Cyber-Physical Systems (CPSs) many simulation based approaches to System Level Formal Verification (SLFV) have been devised. Basically, these are Bounded Model Checking approaches (since simulation horizon is of course bounded) relying on simulators to compute the system dynamics and thereby verify the given system properties. The main obstacle to simulation based SLFV is the large number of simulation scenarios to be considered and thus the huge amount of simulation time needed to complete the verification task. To save on computation time, simulation based SLFV approaches exploit the capability of simulators to save and restore simulation states. Essentially, such a time saving is obtained by optimising the simulation script defining the simulation activity needed to carry out the verification task. Although such approaches aim to (bounded) formal verification, as a matter of fact, the proof of correctness of the methods to optimise simulation scripts basically relies on an intuitive semantics for simulation scripting languages. This hampers the possibility of formally showing that the optimisations introduced to speed up the simulation activity do not actually omit checking of relevant behaviours for the system under verification. The aim of this paper is to fill the above gap by presenting an operational semantics for simulation scripting languages and by proving soundness and completeness properties for it. This, in turn, enables formal proofs of equivalence between unoptimised and optimised simulation scripts. |
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MCLab @ davi @ Mancini2021100640 |
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183 |
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Maggioli, F.; Mancini, T.; Tronci, E. |
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SBML2Modelica: Integrating biochemical models within open-standard simulation ecosystems |
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Journal Article |
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2019 |
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Bioinformatics |
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36 |
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7 |
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2165–2172 |
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SBML is the most widespread language for the definition of biochemical models. Although dozens of SBML simulators are available, there is a general lack of support to the integration of SBML models within open-standard general-purpose simulation ecosystems. This hinders co-simulation and integration of SBML models within larger model networks, in order to, e.g., enable in-silico clinical trials of drugs, pharmacological protocols, or engineering artefacts such as biomedical devices against Virtual Physiological Human models.Modelica is one of the most popular existing open-standard general-purpose simulation languages, supported by many simulators. Modelica models are especially suited for the definition of complex networks of heterogeneous models from virtually all application domains. Models written in Modelica (and in 100+ other languages) can be readily exported into black-box Functional Mock-Up Units (FMUs), and seamlessly co-simulated and integrated into larger model networks within open-standard language-independent simulation ecosystems.In order to enable SBML model integration within heterogeneous model networks, we present SBML2Modelica, a software system translating SBML models into well-structured, user-intelligible, easily modifiable Modelica models. SBML2Modelica is SBML Level 3 Version 2 -compliant and succeeds on 96.47% of the SBML Test Suite Core (with a few rare, intricate, and easily avoidable combinations of constructs unsupported and cleanly signalled to the user). Our experimental campaign on 613 models from the BioModels database (with up to 5438 variables) shows that the major open-source (general-purpose) Modelica and FMU simulators achieve performance comparable to state-of-the-art specialised SBML simulators.SBML2Modelica is written in Java and is freely available for non-commercial use at https://bitbucket.org/mclab/sbml2modelica |
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1367-4803 |
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MCLab @ davi @ ref10.1093/bioinformatics/btz860 |
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179 |
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Leeners, B.; Krueger, T.H.C.; Geraedts, K.; Tronci, E.; Mancini, T.; Egli, M.; Roeblitz, S.; Saleh, L.; Spanaus, K.; Schippert, C.; Zhang, Y.; Ille, F. |
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Associations Between Natural Physiological and Supraphysiological Estradiol Levels and Stress Perception |
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2019 |
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Frontiers in Psychology |
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10 |
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1296 |
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Stress is a risk factor for impaired general, mental and reproductive health. The role of physiological and supraphysiological estradiol concentrations in stress perception and stress processing is less well understood. We therefore, conducted a prospective observational study to investigate the association between estradiol, stress perception and stress-related cognitive performance within serial measurements either during the natural menstrual cycle or during fertility treatment, where estradiol levels are strongly above the physiological level of a natural cycle and consequently, represent a good model to study dose-dependent effects of estradiol. Data from 44 women receiving in vitro fertilization at the Department of Reproductive Endocrinology in Zurich, Switzerland was compared to data from 88 women with measurements during their natural menstrual cycle. The german version of the Perceived Stress Questionnaire (PSQ) and the Cognitive Bias Test (CBT), in which cognitive performance is tested under time stress were used to evaluate subjective and functional aspects of stress. Estradiol levels were investigated at four different time points during the menstrual cycle and at two different time points during a fertility treatment. Cycle phase were associated with PSQ worry and cognitive bias in normally cycling women, but different phases of fertility treatment were not associated with subjectively perceived stress and stress-related cognitive bias. PSQ lack of joy and PSQ demands related to CBT in women receiving fertility treatment but not in women with a normal menstrual cycle. Only strong changes of the estradiol level during fertility treatment were weakly associated with CBT, but not with subjectively experienced stress. Our research emphasises the multidimensional character of stress and the necessity to adjust stress research to the complex nature of stress perception and processing. Infertility is associated with an increased psychological burden in patients. However, not all phases of the process to overcome infertility do significantly increase patient stress levels. Also, research on the psychological burden of infertility should consider that stress may vary during the different phases of fertility treatment. |
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MCLab @ davi @ ref10.3389/fpsyg.2019.01296 |
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178 |
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Sinisi, S.; Alimguzhin, V.; Mancini, T.; Tronci, E.; Mari, F.; Leeners, B. |
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Optimal Personalised Treatment Computation through In Silico Clinical Trials on Patient Digital Twins |
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2020 |
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Fundamenta Informaticae |
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174 |
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283-310 |
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Artificial Intelligence; Virtual Physiological Human; In Silico Clinical Trials; Simulation; Personalised Medicine; In Silico Treatment Optimisation |
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In Silico Clinical Trials (ISCT), i.e. clinical experimental campaigns carried out by means of computer simulations, hold the promise to decrease time and cost for the safety and efficacy assessment of pharmacological treatments, reduce the need for animal and human testing, and enable precision medicine. In this paper we present methods and an algorithm that, by means of extensive computer simulation-based experimental campaigns (ISCT) guided by intelligent search, optimise a pharmacological treatment for an individual patient (precision medicine ). We show the effectiveness of our approach on a case study involving a real pharmacological treatment, namely the downregulation phase of a complex clinical protocol for assisted reproduction in humans. |
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IOS Press |
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1875-8681 |
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MCLab @ davi @ |
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187 |
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Chen, Q.M.; Finzi, A.; Mancini, T.; Melatti, I.; Tronci, E. |
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MILP, Pseudo-Boolean, and OMT Solvers for Optimal Fault-Tolerant Placements of Relay Nodes in Mission Critical Wireless Networks |
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2020 |
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Fundamenta Informaticae |
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174 |
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229-258 |
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In critical infrastructures like airports, much care has to be devoted in protecting radio communication networks from external electromagnetic interference. Protection of such mission-critical radio communication networks is usually tackled by exploiting radiogoniometers: at least three suitably deployed radiogoniometers, and a gateway gathering information from them, permit to monitor and localise sources of electromagnetic emissions that are not supposed to be present in the monitored area. Typically, radiogoniometers are connected to the gateway through relay nodes . As a result, some degree of fault-tolerance for the network of relay nodes is essential in order to offer a reliable monitoring. On the other hand, deployment of relay nodes is typically quite expensive. As a result, we have two conflicting requirements: minimise costs while guaranteeing a given fault-tolerance. In this paper, we address the problem of computing a deployment for relay nodes that minimises the overall cost while at the same time guaranteeing proper working of the network even when some of the relay nodes (up to a given maximum number) become faulty (fault-tolerance ). We show that, by means of a computation-intensive pre-processing on a HPC infrastructure, the above optimisation problem can be encoded as a 0/1 Linear Program, becoming suitable to be approached with standard Artificial Intelligence reasoners like MILP, PB-SAT, and SMT/OMT solvers. Our problem formulation enables us to present experimental results comparing the performance of these three solving technologies on a real case study of a relay node network deployment in areas of the Leonardo da Vinci Airport in Rome, Italy. |
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IOS Press |
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MCLab @ davi @ |
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188 |
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Tortora, L.; Meynen, G.; Bijlsma, J.; Tronci, E.; Ferracuti, S. |
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Neuroprediction and A.I. in Forensic Psychiatry and Criminal Justice: A Neurolaw Perspective |
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2020 |
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Frontiers in Psychology |
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11 |
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220 |
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Advances in the use of neuroimaging in combination with A.I., and specifically the use of machine learning techniques, have led to the development of brain-reading technologies which, in the nearby future, could have many applications, such as lie detection, neuromarketing or brain-computer interfaces. Some of these could, in principle, also be used in forensic psychiatry. The application of these methods in forensic psychiatry could, for instance, be helpful to increase the accuracy of risk assessment and to identify possible interventions. This technique could be referred to as ‘A.I. neuroprediction,’ and involves identifying potential neurocognitive markers for the prediction of recidivism. However, the future implications of this technique and the role of neuroscience and A.I. in violence risk assessment remain to be established. In this paper, we review and analyze the literature concerning the use of brain-reading A.I. for neuroprediction of violence and rearrest to identify possibilities and challenges in the future use of these techniques in the fields of forensic psychiatry and criminal justice, considering legal implications and ethical issues. The analysis suggests that additional research is required on A.I. neuroprediction techniques, and there is still a great need to understand how they can be implemented in risk assessment in the field of forensic psychiatry. Besides the alluring potential of A.I. neuroprediction, we argue that its use in criminal justice and forensic psychiatry should be subjected to thorough harms/benefits analyses not only when these technologies will be fully available, but also while they are being researched and developed. |
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MCLab @ davi @ Neuroprediction-2020 |
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Fischer, S.; Ehrig, R.; Schaefer, S.; Tronci, E.; Mancini, T.; Egli, M.; Ille, F.; Krueger, T.H.C.; Leeners, B.; Roeblitz, S. |
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Mathematical Modeling and Simulation Provides Evidence for New Strategies of Ovarian Stimulation |
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2021 |
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Frontiers in Endocrinology |
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12 |
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117 |
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New approaches to ovarian stimulation protocols, such as luteal start, random start or double stimulation, allow for flexibility in ovarian stimulation at different phases of the menstrual cycle. It has been proposed that the success of these methods is based on the continuous growth of multiple cohorts (“waves”) of follicles throughout the menstrual cycle which leads to the availability of ovarian follicles for ovarian controlled stimulation at several time points. Though several preliminary studies have been published, their scientific evidence has not been considered as being strong enough to integrate these results into routine clinical practice. This work aims at adding further scientific evidence about the efficiency of variable-start protocols and underpinning the theory of follicular waves by using mathematical modeling and numerical simulations. For this purpose, we have modified and coupled two previously published models, one describing the time course of hormones and one describing competitive follicular growth in a normal menstrual cycle. The coupled model is used to test ovarian stimulation protocols in silico. Simulation results show the occurrence of follicles in a wave-like manner during a normal menstrual cycle and qualitatively predict the outcome of ovarian stimulation initiated at different time points of the menstrual cycle. |
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MCLab @ davi @ ref10.3389/fendo.2021.613048 |
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Cesta, Amedeo; Fratini, Simone; Orlandini, Andrea; Finzi, Alberto; Tronci, Enrico |
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Flexible Plan Verification: Feasibility Results |
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2011 |
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Fundamenta Informaticae |
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111-137 |
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Sapienza @ mari @ fi11 |
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