IU Indianapolis ScholarWorks :: Browsing by Subject "Modeling"

Browsing by Subject "Modeling"

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Balanced excitation and inhibition in temperature responses to meth
(Taylor & Francis, 2014-10-30) Molkov, Yaroslav I.; Zaretsky, Dmitry V.; Department of Mathematical Sciences, School of Science
Fatal hyperthermia after administration of various amphetamines is well-known clinical phenomenon, however, there is no consistent theory explaining its etiology and/or pathogenesis. Dose-dependence of temperature responses to methamphetamine is intricate. Recently, using mathematical modeling it was suggested that delicate interplay of excitatory and inhibitory mechanisms underlies this complexity.
Belantamab mafodotin for the treatment of relapsed/refractory multiple myeloma in heavily pretreated patients: a US cost-effectiveness analysis
(Taylor & Francis, 2021) Nikolaou, Andreas; Ambavane, Apoorva; Shah, Anshul; Ma, Wenkang; Tosh, Jon; Kapetanakis, Venediktos; Willson, Jenny; Wang, Feng; Hogea, Cosmina; Gorsh, Boris; Gutierrez, Ben; Sapra, Sandhya; Suvannasankha, Attaya; Samyshkin, Yevgeniy; Medicine, School of Medicine
Background: Patients with relapsed/refractory multiple myeloma (RRMM) require several lines of therapy, with typically shorter remission duration with each additional line. Research design and methods: The cost-effectiveness of belantamab mafodotin (belamaf; DREAMM-2; NCT03525678) was compared with selinexor plus dexamethasone (SEL+DEX; STORM Part 2; NCT02336815) among patients with RRMM who have received at least four prior therapies. The base case used a US commercial payer's perspective over a 10-year time horizon. Efficacy data were based on parametric survival analysis of DREAMM-2 and matching-adjusted indirect treatment comparison between DREAMM-2 and STORM Part 2, which assessed relative treatment effects between belamaf and SEL+DEX. Cost inputs included drug treatment, concomitant medications, adverse event management, subsequent treatments, and disease management. Results: Belamaf decreased total treatment costs per patient by $14,267 and increased patient life years by 0.74 and quality-adjusted life years (QALYs) by 0.49 versus SEL+DEX. Patients receiving belamaf accrued 0.12 fewer progression-free life years versus patients on SEL+DEX. Conclusions: From a US commercial payer's perspective, belamaf had lower costs, and increased QALYs and life-year gain, compared with SEL+DEX. Belamaf is therefore likely to be a cost-effective treatment option for patients with RRMM who have received four or more prior lines of therapy.
Build-A-Pelvis: a Low-cost Modeling Activity to Improve Medical Students’ Understanding of Perineal Anatomy
(Springer, 2019-07-26) Smith, Theodore C.; Husmann, Polly; Medicine, School of Medicine
Background: We demonstrate a low-cost, active learning module that provides medical students with a three-dimensional understanding of perineal anatomy. Activity: Student groups completed a perineal model and then reviewed another group's model of the opposite sex. Multiple pre- and post-module quizzes and correlated exam questions were analyzed. Self-reported understanding of perineal anatomy and usefulness of activity were reported. Results: Students showed significant increases between pre- and post-quiz scores and perceptions of understanding (p < 0.001). Outcomes on exam questions were significantly higher than non-participating counterparts (p = 0.011). Discussion: Thus, this low-cost modeling activity can benefit learning of perineal anatomy.
The challenges of modeling and forecasting the spread of COVID-19
(National Academy of Sciences, 2020-07-02) Bertozzi, Andrea L.; Franco, Elisa; Mohler, George; Short, Martin B.; Sledge, Daniel; Computer and Information Science, School of Science
The coronavirus disease 2019 (COVID-19) pandemic has placed epidemic modeling at the forefront of worldwide public policy making. Nonetheless, modeling and forecasting the spread of COVID-19 remains a challenge. Here, we detail three regional-scale models for forecasting and assessing the course of the pandemic. This work demonstrates the utility of parsimonious models for early-time data and provides an accessible framework for generating policy-relevant insights into its course. We show how these models can be connected to each other and to time series data for a particular region. Capable of measuring and forecasting the impacts of social distancing, these models highlight the dangers of relaxing nonpharmaceutical public health interventions in the absence of a vaccine or antiviral therapies.
Circadian variability of body temperature responses to methamphetamine
(American Physiological Society, 2018-01) Behrouzvaziri, Abolhassan; Zaretskaia, Maria V.; Rusyniak, Daniel E.; Zaretsky, Dmitry V.; Molkov, Yaroslav I.; Mathematical Sciences, School of Science
Vital parameters of living organisms exhibit circadian rhythmicity. Although rats are nocturnal animals, most of the studies involving rats are performed during the day. The objective of this study was to examine the circadian variability of the body temperature responses to methamphetamine. Body temperature was recorded in male Sprague-Dawley rats that received intraperitoneal injections of methamphetamine (Meth, 1 or 5 mg/kg) or saline at 10 AM or at 10 PM. The baseline body temperature at night was 0.8°C higher than during the day. Both during the day and at night, 1 mg/kg of Meth induced monophasic hyperthermia. However, the maximal temperature increase at night was 50% smaller than during the daytime. Injection of 5 mg/kg of Meth during the daytime caused a delayed hyperthermic response. In contrast, the same dose at night produced responses with a tendency toward a decrease of body temperature. Using mathematical modeling, we previously showed that the complex dose dependence of the daytime temperature responses to Meth results from an interplay between inhibitory and excitatory drives. In this study, using our model, we explain the suppression of the hyperthermia in response to Meth at night. First, we found that the baseline activity of the excitatory drive is greater at night. It appears partially saturated and thus is additionally activated by Meth to a lesser extent. Therefore, the excitatory component causes less hyperthermia or becomes overpowered by the inhibitory drive in response to the higher dose. Second, at night the injection of Meth results in reduction of the equilibrium body temperature, leading to gradual cooling counteracting hyperthermia.
Combined reflectance spectroscopy and stochastic modeling approach for noninvasive hemoglobin determination via palpebral conjunctiva
(Wiley, 2014-01-08) Kim, Oleg; McMurdy, John; Jay, Gregory; Lines, Collin; Crawford, Gregory; Alber, Mark; Medicine, School of Medicine
A combination of stochastic photon propagation model in a multilayered human eyelid tissue and reflectance spectroscopy was used to study palpebral conjunctiva spectral reflectance for hemoglobin (Hgb) determination. The developed model is the first biologically relevant model of eyelid tissue, which was shown to provide very good approximation to the measured spectra. Tissue optical parameters were defined using previous histological and microscopy studies of a human eyelid. After calibration of the model parameters the responses of reflectance spectra to Hgb level and blood oxygenation variations were calculated. The stimulated reflectance spectra in adults with normal and low Hgb levels agreed well with experimental data for Hgb concentrations from 8.1 to 16.7 g/dL. The extracted Hgb levels were compared with in vitro Hgb measurements. The root mean square error of cross-validation was 1.64 g/dL. The method was shown to provide 86% sensitivity estimates for clinically diagnosed anemia cases. A combination of the model with spectroscopy measurements provides a new tool for noninvasive study of human conjunctiva to aid in diagnosing blood disorders such as anemia.
Effects of stress-dependent growth on evolution of sulcal direction and curvature in models of cortical folding
(Elsevier, 2023) Balouchzadeh, Ramin; Bayly, Philip V.; Garcia, Kara E.; Radiology and Imaging Sciences, School of Medicine
The majority of human brain folding occurs during the third trimester of gestation. Although many studies have investigated the physical mechanisms of brain folding, a comprehensive understanding of this complex process has not yet been achieved. In mechanical terms, the "differential growth hypothesis" suggests that the formation of folds results from a difference in expansion rates between cortical and subcortical layers, which eventually leads to mechanical instability akin to buckling. It has also been observed that axons, a substantial component of subcortical tissue, can elongate or shrink under tensile or compressive stress, respectively. Previous work has proposed that this cell-scale behavior in aggregate can produce stress-dependent growth in the subcortical layers. The current study investigates the potential role of stress-dependent growth on cortical surface morphology, in particular the variations in folding direction and curvature over the course of development. Evolution of sulcal direction and mid-cortical surface curvature were calculated from finite element simulations of three-dimensional folding in four different initial geometries: (i) sphere; (ii) axisymmetric oblate spheroid; (iii) axisymmetric prolate spheroid; and (iv) triaxial spheroid. The results were compared to mid-cortical surface reconstructions from four preterm human infants, imaged and analyzed at four time points during the period of brain folding. Results indicate that models incorporating subcortical stress-dependent growth predict folding patterns that more closely resemble those in the developing human brain. Statement of significance: Cortical folding is a critical process in human brain development. Aberrant folding is associated with disorders such as autism and schizophrenia, yet our understanding of the physical mechanism of folding remains limited. Ultimately mechanical forces must shape the brain. An important question is whether mechanical forces simply deform tissue elastically, or whether stresses in the tissue modulate growth. Evidence from this paper, consisting of quantitative comparisons between patterns of folding in the developing human brain and corresponding patterns in simulations, supports a key role for stress-dependent growth in cortical folding.
Exploring the role of the Kӧlliker-Fuse nucleus in breathing variability via mathematical modeling
(Wiley, 2024) John, S. R.; Barnett, W. H.; Abdala, A. P. L.; Zoccal, D. B.; Rubin, J. E.; Molkov, Y. I.; Anatomy, Cell Biology and Physiology, School of Medicine
The Kӧlliker-Fuse nucleus (KF), which is part of the parabrachial complex, participates in the generation of eupnea under resting conditions and the control of active abdominal expiration when increased ventilation is required. Moreover, dysfunctions in KF neuronal activity are believed to play a role in the emergence of respiratory abnormalities seen in Rett syndrome (RTT), a progressive neurodevelopmental disorder associated with an irregular breathing pattern and frequent apneas. Relatively little is known, however, about the intrinsic dynamics of neurons within the KF and how their synaptic connections affect breathing pattern control and contribute to breathing irregularities. In this study, we use a reduced computational model to consider several dynamical regimes of KF activity paired with different input sources to determine which combinations are compatible with known experimental observations. We further build on these findings to identify possible interactions between the KF and other components of the respiratory neural circuitry. Specifically, we present two models that both simulate eupneic as well as RTT-like breathing phenotypes. Using nullcline analysis, we identify the types of inhibitory inputs to the KF leading to RTT-like respiratory patterns and suggest possible KF local circuit organizations. When the identified properties are present, the two models also exhibit quantal acceleration of late-expiratory activity, a hallmark of active expiration featuring forced exhalation, with increasing inhibition to KF, as reported experimentally. Hence, these models instantiate plausible hypotheses about possible KF dynamics and forms of local network interactions, thus providing a general framework as well as specific predictions for future experimental testing.
Modeling of machining process of EB-PVD ceramic coatings using discrete element method
(Elsevier, 2022-08) Zhang, Jian; Sagar, Sugrim; Dube, Tejsh; Yang, Xuehui; Choi, Hyunhee; Jung, Yeon-Gil; Koo, Dan Daehyun; Zhang, Jing; Mechanical and Energy Engineering, School of Engineering and Technology
In this work, a new discrete element model (DEM) for simulating the machining process of thermal barrier coatings is presented. The effects of cutting processing parameters, including cutting depth and cutting speed, on the cutting force and chip morphology are studied. In the model, a columnar grain microstructure mimicking the electron-beam physical vapor deposition (EB-PVD) coating is used. The results show that, as the cutting depth increases, the cutting chip morphology changes from fine powder form (ductile mode) to large chuck pieces (brittle mode). The transition depth or the critical cutting depth is determined based on the Griffith fracture criterion. The transition is also illustrated using the numbers of broken bonds and cutting energy changes in the DEM model. In the ductile mode, the number of broken bonds is increased gradually. In contrast, at larger cutting depths, the brittle mode causes a step-wise increase. Moreover, the maximum cutting force is found correlated to the cutting depth, which agrees well with an analytical solution based on fracture mechanics principles. The period in the cutting force is consistent with the diameter of the column grain. Finally, the cutting speed has little effect on the cutting force and chip morphology due to no strain rate sensitivity.
Modeling of Temperature Swing Effect in Silica Reinforced Porous Anodized Aluminum Based Thermal Barrier Coating
(SAE International, 2021) Gulhane, Abhilash; Zhang, Jian; Yang, Xuehui; Lu, Zhe; Park, Hye-Yeong; Jung, Yeon-Gil; Li, Yafeng; Zhang, Jing; Mechanical and Energy Engineering, School of Engineering and Technology
This paper presents a finite element (FE) based model to simulate the temperature swing phenomenon of Silica Reinforced Porous Anodized Aluminum (SiRPA) thermal barrier coatings (TBCs). A realistic 3D SiRPA coating microstructure is constructed, based on the morphology of an experimentally grown coating structure, and the known relationship of geometry and anodization parameters. The coatings’ thermophysical properties are first computed using the FE model. The predicted thermal conductivity, thermal diffusivity, and bulk density are compared well with the experimental values. Also, transient thermal analysis is conducted to model the temperature swing effect of the coating by comparing the temperature fluctuation of SiRPA coating with conventional Yttria Stabilized Zirconia (YSZ) based TBCs. With the predicted thermophysical properties, the model is capable to predict the “temperature swing” effect of SiRPA by a transient thermal analysis. Temperature fluctuation of SiRPA is found greater compared to YSZ coating, suggesting its applicability in internal combustion engines. The porosity-dependent thermal conductivity of SiRPA coating is numerically derived. The thermal conductivity decreases linearly with increasing total porosity. The modeling data illustrate that the SiRPA coating shows a higher fluctuation compared to YSZ based TBCs, suggesting its applicability in internal combustion engines.

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