Using musculoskeletal models to estimate in vivo total knee replacement kinematics and loads: effect of differences between models

Total knee replacement (TKR) is one of the most performed orthopedic surgeries to treat knee joint diseases in the elderly population. Although the survivorship of knee implants may extend beyond two decades, the poor outcome rate remains considerable. A recent computational approach used to better understand failure modes and improve TKR outcomes is based on the combination of musculoskeletal (MSK) and finite element models. This combined multiscale modeling approach is a promising strategy in the field of computational biomechanics; however, some critical aspects need to be investigated. In particular, the identification and quantification of the uncertainties related to the boundary conditions used as inputs to the finite element model due to a different definition of the MSK model are crucial. Therefore, the aim of this study is to investigate this problem, which is relevant for the model credibility assessment process. Three different generic MSK models available in the OpenSim platform were used to simulate gait, based on the experimental data from the fifth edition of the “Grand Challenge Competitions to Predict in vivo Knee Loads.” The outputs of the MSK analyses were compared in terms of relative kinematics of the knee implant components and joint reaction (JR) forces and moments acting on the tibial insert. Additionally, the estimated knee JRs were compared with those measured by the instrumented knee implant so that the “global goodness of fit” was quantified for each model. Our results indicated that the different kinematic definitions of the knee joint and the muscle model implemented in the different MSK models influenced both the motion and the load history of the artificial joint. This study demonstrates the importance of examining the influence of the model assumptions on the output results and represents the first step for future studies that will investigate how the uncertainties in the MSK models propagate on disease-specific finite element model results

Experimental validation of a subject-specific finite element model of lumbar spine segment using digital image correlation

Pathologies such as cancer metastasis and osteoporosis strongly affect the mechanical properties of the vertebral bone and increase the risk of fragility fractures. The prediction of the fracture risk with a patient-specific model, directly generated from the diagnostic images of the patient, could help the clinician in the choice of the correct therapy to follow. But before such models can be used to support any clinical decision, their credibility must be demonstrated through verification, validation, and uncertainty quantification. In this study we describe a procedure for the generation of such patient-specific finite element models and present a first validation of the kinematics of the spine segment. Quantitative computed tomography images of a cadaveric lumbar spine segment presenting vertebral metastatic lesions were used to generate the model. The applied boundary conditions replicated a specific experimental test where the spine segment was loaded in compression-flexion. Model predictions in terms of vertebral surface displacements were compared against the full-field experimental displacements measured with Digital Image Correlation. A good agreement was obtained from the local comparison between experimental data and simulation results (R2 > 0.9 and RMSE% <8%). In conclusion, this work demonstrates the possibility to apply the developed modelling pipeline to predict the displacement field of human spine segment under physiological loading conditions, which is a first fundamental step in the credibility assessment of these clinical decision-support technology

A Mathematical Model of a Solar Collector Augmented by a Flat Plate above Reflector: Optimum Inclination of Collector and Reflector

In this study a theoretical analysis of a collector augmented by a bottom booster reflector is presented. An analytical model has been developed and used to estimate the solar irradiation passing through the transparent cover of a flat collector, both with and without a bottom reflector. The analytical model is based on the anisotropic sky model and takes into account a finite length system with different angular configurations and reciprocal shading and reflections between reflector and collector. Computer simulations have been carried out in order to find the optimum angles of the reflector with respect to the plane of the collector. Optimal inclinations of the collector and reflector for each month at 39° N latitude have been identified

Microwaves as Diagnostic Tool for Pituitary Tumors: Preliminary Investigations

To date, tumors, the second cause of death worldwide, are a modern medicine plight. The development of rapid, cost-effective and reliable prevention and diagnostics tools is mandatory to support clinicians and ensure patients' adequate intervention. Pituitary tumors are a class of neoplasm, which calls for suitable and ad hoc diagnostic tools. Recently, microwaves have gained interest as a non-ionizing, non-invasive valuable diagnostic approach for identifying pathologic tissues according to their dielectric properties. This work deals with the preliminary investigation of the feasibility of using microwaves to diagnose pituitary tumors. In particular, it focuses on benign tumors of the adenohypophysis, e.g., the pituitary adenomas. It is assumed to access the region of interest of the pituitary region by following a trans-sphenoidal approach. The problem was modeled by developing an equivalent transmission line model of the multi-layered, lossy tissues (front bone of sphenoid sinuses, air in the sinuses, posterior bone of sphenoid sinuses, the pituitary gland and the tumor). The forward problem was developed to investigate the transmission coefficient for identifying the most favorable propagation conditions. Then, it was analyzed if, by the solution of an inverse problem, it is possible to reconstruct the permittivity and electrical conductivity profiles and identify the tumor presence. The results are promising since a maximum reconstruction error of 8% is found, in the worst case, thus paving the way for the use of microwaves for the diagnosis of pituitary tumors

Generation of Free Carriers in MoSe2 Monolayers Via Energy Transfer from CsPbBr3 Nanocrystals

Transition metal dichalcogenide (TMDCs) monolayers make an excellent component in optoelectronic devices such as photodetectors and phototransistors. Selenide-based TMDCs, specifically molybdenum diselenide (MoSe2) monolayers with low defect densities, show much faster photoresponses compared to their sulfide counterpart. However, the typically low absorption of the atomically thin MoSe2 monolayer and high exciton binding energy limit the photogeneration of charge carriers. Yet, integration of light-harvesting materials with TMDCs can produce increased photocurrents via energy transfer. In this article, it is demonstrated that the interaction of cesium lead bromide (CsPbBr3) nanocrystals with MoSe2 monolayers results into an energy transfer efficiency of over 86%, as ascertained from the quenching and decay dynamics of the CsPbBr3 nanocrystals emission. Notably, the increase in the MoSe2 monolayer emission in the heterostructure accounts only for 33% of the transferred energy. It is found that part of the excess energy generates directly free carriers in the MoSe2 monolayer, as a result of the transfer of energy into the exciton continuum. The efficiency of the heterostructure via enhanced photocurrents with respect to the single material unit is proven. These results demonstrate a viable route to overcome the high exciton binding energy typical for TMDCs, as such having an impact on optoelectronic processes that rely on efficient exciton dissociation

Three-Body Dynamics and Self-Powering of an Electrodynamic Tether in a Plasmasphere

The dynamics of an electrodynamic tether in a three-body gravitational environment are investigated. In the classical two-body scenario the extraction of power is at the expense of orbital kinetic energy. As a result of power extraction, an electrodynamic tether satellite system loses altitude and deorbits. This concept has been proposed and well investigated in the past, for example for orbital debris mitigation and spent stages reentry. On the other hand, in the three-body scenario an electrodynamic tether can be placed in an equilibrium position fixed with respect to the two primary bodies without deorbiting, and at the same time generate power for onboard use. The appearance of new equilibrium positions in the perturbed three-body problem allow this to happen as the electrical power is extracted at the expenses of the plasma corotating with the primary body. Fundamental differences between the classical twobody dynamics and the new phenomena appearing in the circular restricted three-body problem perturbed by the electrodynamic force of the electrodynamic tether are shown in the paper. An interesting application of an electrodynamic tether placed in the Jupiter plasma torus is then considered, in which the electrodynamic tether generates useful electrical power of about 1 kW with a 20-km-long electrodynamic tether from the environmental plasma without losing orbital energy

Quantifying signal changes in nano-wire based biosensors

In this work, we present a computational methodology for predicting the change in signal (conductance sensitivity) of a nano-BioFET sensor (a sensor based on a biomolecule binding another biomolecule attached to a nano-wire field effect transistor) upon binding its target molecule. The methodology is a combination of the screening model of surface charge sensors in liquids developed by Brandbyge and co-workers [Sørensen et al., Appl. Phys. Lett., 2007, 91, 102105], with the PROPKA method for predicting the pH-dependent charge of proteins and protein-ligand complexes, developed by Jensen and co-workers [Li et al., Proteins: Struct., Funct., Bioinf., 2005, 61, 704-721, Bas et al., Proteins: Struct., Funct., Bioinf., 2008, 73, 765-783]. The predicted change in conductance sensitivity based on this methodology is compared to previously published data on nano-BioFET sensors obtained by other groups. In addition, the conductance sensitivity dependence from various parameters is explored for a standard wire, representative of a typical experimental setup. In general, the experimental data can be reproduced with sufficient accuracy to help interpret them. The method has the potential for even more quantitative predictions when key experimental parameters (such as the charge carrier density of the nano-wire or receptor density on the device surface) can be determined (and reported) more accurately. © 2011 The Royal Society of Chemistry

Possible Contexts of Use for In Silico trials methodologies: a consensus- based review

The term In Silico Trial indicates the use of computer modelling and simulation to evaluate the safety and efficacy of a medical product, whether a drug, a medical device, a diagnostic product or an advanced therapy medicinal product. Predictive models are positioned as new methodologies for the development and the regulatory evaluation of medical products. New methodologies are qualified by regulators such as FDA and EMA through formal processes, where a first step is the definition of the Context of Use (CoU), which is a concise description of how the new methodology is intended to be used in the development and regulatory assessment process. As In Silico Trials are a disruptively innovative class of new methodologies, it is important to have a list of possible CoUs highlighting potential applications for the development of the relative regulatory science. This review paper presents the result of a consensus process that took place in the InSilicoWorld Community of Practice, an online forum for experts in in silico medicine. The experts involved identified 46 descriptions of possible CoUs which were organised into a candidate taxonomy of nine CoU categories. Examples of 31 CoUs were identified in the available literature; the remaining 15 should, for now, be considered speculative

Production of Aluminum Stabilized Superconducting Cable for the Mu2e Transport Solenoid

The Fermilab Mu2e experiment [1] , [2] , currently under construction at Fermilab, has the goal of measuring the rare process of direct muon to electron conversion in the field of a nucleus. The experiment features three large superconducting solenoids: the production solenoid (PS), the transport solenoid (TS), and the detector solenoid (DS). The TS is an "S-shaped" solenoid that sits in between the PS and the DS producing a magnetic field ranging between 2.5 and 2.0 T. This paper describes the various steps that led to the successful procurement of over 740 km of superconducting wire and 44 km of Al-stabilized Rutherford cable needed to build the 52 coils that constitute the Mu2e TS cold mass. The main cable properties and results of electrical and mechanical test campaigns are summarized and discussed. Critical current measurements of the Al-stabilized cables are presented and compared to expected critical current values as measured on extracted strands from the final cables after chemical etching of the aluminum stabilizer. A robust and reliable approach to cable welding is presented, and the effect of cable bending on the transport current is also investigated and presented

Toward a Regulatory Pathway for the Use of in Silico Trials in The Ce Marking of Medical Devices

In Silico Trials methodologies will play a growing and fundamental role in the development and de-risking of new medical devices in the future. While the regulatory pathway for Digital Patient and Personal Health Forecasting solutions is clear, it is more complex for In Silico Trials solutions, and therefore deserves a deeper analysis. In this position paper, we investigate the current state of the art towards the regulatory system for in silico trials applied to medical devices while exploring the European regulatory system toward this topic. We suggest that the European regulatory system should start a process of innovation: in principle to limit distorted quality by different internal processes within notified bodies, hence avoiding that the more innovative and competitive companies focus their attention on the needs of other large markets, like the USA, where the use of such radical innovations is already rapidly developing