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Two different approaches for the linear-time solution of three-dimensional magnetostatic field problems encompassing large-scale linear systems with millions of degrees of freedom are presented. The $\varphi $ –method is formulated in terms of nodal variables, i.e., magnetic scalar potentials, and involves the solution of a curl-curl linear system for pre-processing and of a div-grad linear system. The A–method is formulated in terms of edge variables, i.e., line integrals of the magnetic vector potential, and involves the solution of a curl-curl linear system only. It is shown that these linear systems can be solved by flexible conjugate gradient in combination with the aggregation-based multigrid preconditioner (AGMG), tailored for div-grad problems, and with the aggregation-based (auxiliary-space) multigrid preconditioner (AGMG_CC), tailored for curl-curl problems. The robustness and efficiency of these solvers is illustrated using magnetostatic problems of practical interest, with linear or nonlinear media and having parts with complex geometry. Numerical results show that both AGMG and AGMG_CC are able to attain linear solution time in all cases considered, while being both faster and more robust than state-of-the-art algebraic multigrid solvers and preconditioned Krylov subspace solvers, typically adopted in commercial finite element software for electromagnetic analysis.

The linkage between the thrust for national unity and recovery of the lost independence represents the specific feature of Venice in the 1848 revolution and explains the stubborn will to fight. The lagoon after all, is the real strategic and geographical centre of gravity of the war in Italy. It would be necessary for the Italians to exploit in an effective way its position and its potential to defeat Austria. To neutralize it is the premise of any counter move of the Empire. Even if slowly, Venice deploys men and means adequate to the challenge, but the inability of the Savoy regime to understand this linkage and to appreciate the maritime dimension of the conflict, responsibility shared by the top ranks of Venice, allows the return of the Empire and its final victory.

The latency between traumatic brain injury (TBI) and the onset of epilepsy (PTE) represents an opportunity for counteracting epileptogenesis. Antiepileptogenesis trials are hampered by the lack of sensitive biomarkers that allow to enrich patient's population at-risk for PTE. We aimed to assess whether specific ECoG signals predict PTE in a clinically relevant mouse model with ∼60% epilepsy incidence. TBI was provoked in adult CD1 male mice by controlled cortical impact on the left parieto-temporal cortex, then mice were implanted with two perilesional cortical screw electrodes and two similar electrodes in the hemisphere contralateral to the lesion site. Acute seizures and spikes/sharp waves were ECoG-recorded during 1 week post-TBI. These early ECoG events were analyzed according to PTE incidence as assessed by measuring spontaneous recurrent seizures (SRS) at 5 months post-TBI. We found that incidence, number and duration of acute seizures during 3 days post-TBI were similar in PTE mice and mice not developing epilepsy (No SRS mice). Control mice with cortical electrodes (naïve, n = 5) or with electrodes and craniotomy (sham, n = 5) exhibited acute seizures but did not develop epilepsy. The daily number of spikes/sharp waves at the perilesional electrodes was increased similarly in PTE (n = 15) and No SRS (n = 8) mice vs controls (p

Traumatic brain injury (TBI) is a major worldwide neurological disorder with no neuroprotective treatment available. Three-dimensional (3D) in vitro models of brain contusion serving as a screening platform for drug testing are lacking. Here we developed a new in vitro model of brain contusion on organotypic cortical brain slices and tested its responsiveness to mesenchymal stromal cell (MSC) derived secretome. A focal TBI was induced on organotypic slices by an electromagnetic impactor. Compared to control condition, a temporal increase in cell death was observed after TBI by propidium iodide incorporation and lactate dehydrogenase release assays up to 48 h post-injury. TBI induced gross neuronal loss in the lesion core, with disruption of neuronal arborizations measured by microtubule-associated protein-2 (MAP-2) immunostaining and associated with MAP-2 gene down-regulation. Neuronal damage was confirmed by increased levels of neurofilament light chain (NfL), microtubule associated protein (Tau) and ubiquitin C-terminal hydrolase L1 (UCH-L1) released into the culture medium 48 h after TBI. We detected glial activation with microglia cells acquiring an amoeboid shape with less ramified morphology in the contusion core. MSC-secretome treatment, delivered 1 h post-injury, reduced cell death in the contusion core, decreased NfL release in the culture media, promoted neuronal reorganization and improved microglia survival/activation. Our 3D in vitro model of brain contusion recapitulates key features of TBI pathology. We showed protective effects of MSC-secretome, suggesting the model stands as a tractable medium/high throughput, ethically viable, and pathomimetic biological asset for testing new cell-based therapies.

Introduction A significant environmental risk factor for neurodegenerative disease is traumatic brain injury (TBI). However, it is not clear how TBI results in ongoing chronic neurodegeneration. Animal studies show that systemic inflammation is signalled to the brain. This can result in sustained and aggressive microglial activation, which in turn is associated with widespread neurodegeneration. We aim to evaluate systemic inflammation as a mediator of ongoing neurodegeneration after TBI.Methods and analysis TBI-braINFLAMM will combine data already collected from two large prospective TBI studies. The CREACTIVE study, a broad consortium which enrolled >8000 patients with TBI to have CT scans and blood samples in the hyperacute period, has data available from 854 patients. The BIO-AX-TBI study recruited 311 patients to have acute CT scans, longitudinal blood samples and longitudinal MRI brain scans. The BIO-AX-TBI study also has data from 102 healthy and 24 non-TBI trauma controls, comprising blood samples (both control groups) and MRI scans (healthy controls only). All blood samples from BIO-AX-TBI and CREACTIVE have already been tested for neuronal injury markers (GFAP, tau and NfL), and CREACTIVE blood samples have been tested for inflammatory cytokines. We will additionally test inflammatory cytokine levels from the already collected longitudinal blood samples in the BIO-AX-TBI study, as well as matched microdialysate and blood samples taken during the acute period from a subgroup of patients with TBI (n=18).We will use this unique dataset to characterise post-TBI systemic inflammation, and its relationships with injury severity and ongoing neurodegeneration.Ethics and dissemination Ethical approval for this study has been granted by the London—Camberwell St Giles Research Ethics Committee (17/LO/2066). Results will be submitted for publication in peer-review journals, presented at conferences and inform the design of larger observational and experimental medicine studies assessing the role and management of post-TBI systemic inflammation.

The fast solution of three-dimensional eddy current problems is still an open problem, especially when real-size finite element models with millions of degrees of freedom are considered. In order to lower the number of degrees of freedom a magnetic scalar potential can be used in the insulating parts of the model. This may become difficult when the model geometry presents some conductive parts which are multiply connected. In this work a multigrid-based algoritm is proposed that allows for a calculation in linear-time of cohomology, which is needed to introduce the scalar potential without cuts. This algorithm relies on an algebraic multigrid solver for curl-curl field problems, which ensures optimal computational complexity. Numerical results show that the novel algorithm outperforms state-of-the-art methods for cohomology generation based on homological algebra. In addition, based on this algoritm, novel $a,v$ - $\varphi $ and $t$ - $\varphi $ formulations to analyze three-dimensional eddy current problems in multiply connected domains are proposed. Both formulations, after discretization by the cell method, lead to a complex symmetric system of linear equations amenable to fast iterative solution by Krylov-subspace solvers. These formulations are able to provide very accurate numerical results, with a minimum amount of degrees of freedoms to represent the eddy current model. In this way the computational performance is improved compared to the classical $A,V$ - $A$ formulation typically implemented in finite element software for electromagnetic design.

Abstract Background Hip fracture is one of the most common orthopedic causes of hospital admission in frail elderly patients. Hip fracture fixation in this class of patients is considered a high-risk procedure. Preoperative physical examination, plasma natriuretic peptide levels (BNP, Pro-BNP), and cardiovascular scoring systems (ASA-PS, RCRI, NSQIP-MICA) have all been demonstrated to underestimate the risk of postoperative complications. We designed a prospective multicenter observational study to assess whether preoperative lung ultrasound examination can predict better postoperative events thanks to the additional information they provide in the form of “indirect” and “direct” cardiac and pulmonary lung ultrasound signs. Methods LUSHIP is an Italian multicenter prospective observational study. Patients will be recruited on a nation-wide scale in the 12 participating centers. Patients aged > 65 years undergoing spinal anesthesia for hip fracture fixation will be enrolled. A lung ultrasound score (LUS) will be generated based on the examination of six areas of each lung and ascribing to each area one of the four recognized aeration patterns—each of which is assigned a subscore of 0, 1, 2, or 3. Thus, the total score will have the potential to range from a minimum of 0 to a maximum of 36. The association between 30-day postoperative complications of cardiac and/or pulmonary origin and the overall mortality will be studied. Considering the fact that cardiac complications in patients undergoing hip surgery occur in approx. 30% of cases, to achieve 80% statistical power, we will need a sample size of 877 patients considering a relative risk of 1.5. Conclusions Lung ultrasound (LU), as a tool within the anesthesiologist’s armamentarium, is becoming increasingly widespread, and its use in the preoperative setting is also starting to become more common. Should the study demonstrate the ability of LU to predict postoperative cardiac and pulmonary complications in hip fracture patients, a randomized clinical trial will be designed with the scope of improving patient outcome. Trial registration ClinicalTrials.gov, NCT04074876. Registered on August 30, 2019.

The control of Terraferma by road and riverine communication it was a geopolitical imperative for Venetian strategy. Especially the need to command the rivers was imposed by the same It was imposed by the geographic nature of the Lagoon City as well as of the Stato di Terra for assuring the Republic’s security and prosperity. The Lagoon, indeed, is commanded by the many (and often navigable, particularly at the time of the Serenissima) rivers of the Po Valley, as the interruption or dryness of the Padani rivers could even cause the lagoon to disappear, thereafter needing an efficient defense and maintenance. At the same time, they were essential to fuel the wealth of the maritime state built by the Venetians. In fact, the rivers constituted the interconnection of the long-distance sea routes, on which international trading flowed. The state and the maritime power of Venice can only be understood by taking into serious consideration the importance of the rivers, which influenced the Republic’s decisions in every phase of its existence, but particularly during the great expansion into the mainland in the fifteenth century.

Abstract Post-traumatic epilepsy (PTE) accounts for 5% of all epilepsies and 10–20% of the acquired forms. The latency between traumatic brain injury (TBI) and epilepsy onset in high-risk patients offers a therapeutic window for intervention to prevent or improve the disease course. However, progress towards effective treatments has been hampered by the lack of sensitive prognostic biomarkers of PTE, and of therapeutic targets. There is therefore a pressing clinical need for preclinical PTE models suitable for biomarker discovery and drug testing. We characterized in-depth a model of severe TBI induced by controlled cortical impact evolving into PTE in CD1 adult male mice. To identify sensitive measures predictive of PTE development and severity, TBI mice were longitudinally monitored by video-electrocorticography (ECoG), examined by MRI, and tested for sensorimotor and cognitive deficits and locomotor activity. At the end of the video-ECoG recording mice were killed for brain histological analysis. PTE occurred in 58% of mice with frequent motor seizures (one seizure every other day), as determined up to 5 months post-TBI. The weight loss of PTE mice in 1 week after TBI correlated with the number of spontaneous seizures at 5 months. Moreover, the recovery rate of the sensorimotor deficit detected by the SNAP test before the predicted time of epilepsy onset was significantly lower in PTE mice than in those without epilepsy. Neuroscore, beam walk and cognitive deficit were similar in all TBI mice. The increase in the contusion volume, the volume of forebrain regions contralateral to the lesioned hemisphere and white matter changes over time assessed by MRI were similar in PTE and no-PTE mice. However, brain histology showed a more pronounced neuronal cell loss in the cortex and hippocampus contralateral to the injured hemisphere in PTE than in no-PTE mice. The extensive functional and neuropathological characterization of this TBI model, provides a tool to identify sensitive measures of epilepsy development and severity clinically useful for increasing PTE prediction in high-risk TBI patients. The high PTE incidence and spontaneous seizures frequency in mice provide an ideal model for biomarker discovery and for testing new drugs.

We present a novel a,v-q hybrid method for solving large-scale time-harmonic eddy-current problems. This method combines a hybrid unsymmetric formulation based on the cell method and the boundary element method with a hierarchical matrix-compression technique based on randomized singular value decomposition. The main advantage is that the memory requirements are strongly reduced compared to the corresponding hybrid method without matrix compression while retaining the same robust solution strategy consisting of a simple construction of the preconditioner. In addition, the matrix-compression accuracy and efficiency are enhanced compared to traditional compression methods, such as adaptive cross approximation. The numerical results show that the proposed hybrid approach can also be effectively used to analyze large-scale eddy-current problems of engineering interest.

A novel mortar approach for the domain decomposition of field problems discretized in terms of nodal variables by the cell method is here proposed. This approach allows the use of both arbitrary polyhedral meshes and non-conforming discretizations, without limitations or complications due to the mesh type or the model geometry. Therefore, it provides a new domain decomposition method that can be practically used in engineering applications for coupling different parts of a model, which can be independently discretized and then reassembled together. More precisely: 1) Any part of the computational domain is first separately modeled in order to assess the mesh type and size that are best suited for ensuring an accurate local field reconstruction; 2) The different discretized parts can be combined together in order to obtain an accurate solution of a composite problem, while maintaining the local discretizations already determined. As a main advantage over existing mortar approaches, the algebraic structure of the final matrix system-derived by the cell method discretization-is not altered by the introduction of mortar interface conditions. As a result, the same preconditioning and iterative solver strategy can be extended as is to the proposed mortar method. This approach is validated by a convergence analysis on an analytical test case and its effectiveness for practical applications is assessed on a real-sized engineering problem.

A hybrid $a - \varphi $ Cell Method formulation for solving eddy–current problems in 3–D multiply–connected regions is presented. By using the magnetic scalar potential the number of degrees of freedom in the exterior domain with respect to the $A,V - A$ formulation, typically implemented in commercial software for electromagnetic design, can be almost halved. On the other hand, the use of the magnetic vector potential in the interior domain improves the flexibility with respect to $T - \Omega $ formulation, since both conductive and magnetic parts can be easily modeled. By using a Cell Method variant, based on an augmented dual grid for discretization, electric and magnetic variables can be consistently coupled at the interface between interior and exterior domain. Global basis functions needed for representing the magnetic field in the insulating region are obtained by using for the first time iterative solvers relying on auxiliary space preconditioner and aggregation–based algebraic multigrid, with linear optimal complexity. These represent highly–efficient alternatives to traditional computational topology algorithms based on the concept of thick cut. As a result, an indefinite symmetric matrix system, amenable to fast iterative solution, is obtained. Numerical tests show high accuracy and fast convergence of the $a - \varphi $ method on test cases with complex topology. Computational cost for both matrix assembly and linear system solution is limited even for large problems. Comparisons show that the $a - \varphi $ method provides better performance than existing methods such as $A,V - A$ and $h - \varphi $ .

Aneurysmal subarachnoid hemorrhage (SAH) is a substantial cause of mortality and morbidity worldwide. Moreover, survivors after the initial bleeding are often subject to secondary brain injuries and delayed cerebral ischemia, further increasing the risk of a poor outcome. In recent years, the renin–angiotensin system (RAS) has been proposed as a target pathway for therapeutic interventions after brain injury. The RAS is a complex system of biochemical reactions critical for several systemic functions, namely, inflammation, vascular tone, endothelial activation, water balance, fibrosis, and apoptosis. The RAS system is classically divided into a pro-inflammatory axis, mediated by angiotensin (Ang)-II and its specific receptor AT1R, and a counterbalancing system, presented in humans as Ang-(1–7) and its receptor, MasR. Experimental data suggest that upregulation of the Ang-(1–7)/MasR axis might be neuroprotective in numerous pathological conditions, namely, ischemic stroke, cognitive disorders, Parkinson’s disease, and depression. In the presence of SAH, Ang-(1–7)/MasR neuroprotective and modulating properties could help reduce brain damage by acting on neuroinflammation, and through direct vascular and anti-thrombotic effects. Here we review the role of RAS in brain ischemia, with specific focus on SAH and the therapeutic potential of Ang-(1–7).

A novel h-φ approach for solving 3-D time-harmonic eddy current problems is presented. It makes it possible to limit the number of degrees of freedom required for the discretization such as the T-Ω method, while overcoming topological issues related to it when multiply connected domains are considered. Global basis functions, needed for representing magnetic field in the insulating region, are obtained by a fast iterative solver. The computation of thick cuts by high-complexity computational topology tools, typically required by the T-Ω method, is thus avoided. The final matrix system turns out to be symmetric and full-rank unlike the more classical A-A method, which requires gauging of magnetic vector potential to ensure uniqueness. Numerical tests show that the proposed method is accurate and the field problem solution is obtained in a reasonable computational time even for 3-D models with millions of mesh elements.

Recently, there have been significant developments in the field of vibration energy harvesters to feed sensors for structural health monitoring in aeronautics and other high technology fields. Within the framework of the EU InComEss project, new eco-friendly piezoelectric materials are under development. A foreseen application is vibration energy harvesting from the wing slats of aircraft. Semi-analytical models of the vibrating slat make it possible to estimate the maximum voltage that can be generated by a piezoelectric patch bonded to a slat surface. A more detailed analysis must consider details of the three-dimensional geometry of both the harvester and the bonding layer. This can only be carried out with multiphysics finite element software. A finite element model of a whole slat would require a large computational effort as millions of elements are typically needed to model very thin piezoelectric layers. To simplify this analysis, an integrated analytical–numerical method is proposed in this paper. A large-scale analytical model of the whole slat was used to calculate loads on the portion of the slat where a piezoelectric patch was attached. Then, a small-scale finite element model of the portion of the slat with the piezoelectric patch was used to calculate the open circuit voltage generated by the patch. The response of the harvester to random excitation, typical of aeronautic applications, was calculated. The effects of the details of the harvester design on the generated voltage were analyzed and discussed.

Abstract We aimed to evaluate the quality of clinical evidence that substantiated approval of cancer medicines by the European Medicines Agency (EMA) in the last decade. We performed a systematic review and data synthesis of EMA documents in agreement with PRISMA guidelines. We included the European Public Assessment Reports, Summaries of Product Characteristics, and published randomized controlled trials (RCTs) on anti‐cancer drugs approved by EMA from 2010 to 2019, and excluded drugs not indicated for targeting solid or hematological tumors and non‐innovative treatments. We synthesized frequencies of approvals differentiating between unblinded and blinded RCTs with and without overall survival (OS) as a predefined primary outcome measure. We assessed the frequency of post‐approval RCTs for indications without at least one RCT at the time of approval. Of 199 approvals, 159 (80%) were supported by at least one RCT, 63 (32%) by at least one RCT having OS as the primary or co‐primary endpoint, 74 (37%) by at least one blinded RCT, and 30 (15%) by at least one blinded RCT having OS as the primary or co‐primary endpoint. Whereas 40 approvals (20%) were not supported by any RCT and, of those, 9 (22%) were followed by a post‐approval RCT. While the majority of approvals of cancer medicines approved by EMA was supported by at least one RCT, we noted substantial methodological heterogeneity of the studies. Clinical trial registration: PROSPERO registration number CRD42020206669.

A parametric model order reduction method combined with a polynomial spectral approximation is applied for the first time to a Volume Integral Equation method accelerated by a low-rank matrix compression technique. Such an approach allows for drastically reducing the computational cost required by uncertainty quantifications in electromagnetic problems. Moreover, the proposed numerical tool can be adopted for computing stochastic information (e.g. mean, variance, probability density function) of any electromagnetic quantity of interest, in order to test the reliability of industrial devices with uncertainties on the material parameters. Conductive, dielectric, and magnetic media which exhibit uncorrelated and correlated random material parameters are considered by the proposed method.

Introduction and aims Traumatic brain injury (TBI) often results in persistent disability, due particularly to cognitive impairments. Outcomes remain difficult to predict but appear to relate to axonal injury. Several new approaches involving fluid and neuroimaging biomarkers show promise to sensitively quantify axonal injury. By assessing these longitudinally in a large cohort, we aim both to improve our understanding of the pathophysiology of TBI, and provide better tools to predict clinical outcome.Methods and analysis BIOmarkers of AXonal injury after TBI is a prospective longitudinal study of fluid and neuroimaging biomarkers of axonal injury after moderate-to-severe TBI, currently being conducted across multiple European centres. We will provide a detailed characterisation of axonal injury after TBI, using fluid (such as plasma/microdialysate neurofilament light) and neuroimaging biomarkers (including diffusion tensor MRI), which will then be related to detailed clinical, cognitive and functional outcome measures. We aim to recruit at least 250 patients, including 40 with cerebral microdialysis performed, with serial assessments performed twice in the first 10 days after injury, subacutely at 10 days to 6 weeks, at 6 and 12 months after injury.Ethics and dissemination The relevant ethical approvals have been granted by the following ethics committees: in London, by the Camberwell St Giles Research Ethics Committee; in Policlinico (Milan), by the Comitato Etico Milano Area 2; in Niguarda (Milan), by the Comitato Etico Milano Area 3; in Careggi (Florence), by the Comitato Etico Regionale per la Sperimentazione Clinica della Regione Toscana, Sezione area vasta centro; in Trento, by the Trento Comitato Etico per le Sperimentazioni Cliniche, Azienda Provinciale per i Servizi Sanitari della Provincia autonoma di Trento; in Lausanne, by the Commission cantonale d’éthique de la recherche sur l’être humain; in Ljubljana, by the National Medical Ethics Committee at the Ministry of Health of the Republic of Slovenia. The study findings will be disseminated to patients, healthcare professionals, academics and policy-makers including through presentation at conferences and peer-reviewed publications. Data will be shared with approved researchers to provide further insights for patient benefit.Trial registration number NCT03534154.

Vibration energy harvesters in industrial applications usually take the form of cantilever oscillators covered by a layer of piezoelectric material and exploit the resonance phenomenon to improve the generated power. In many aeronautical applications, the installation of cantilever harvesters is not possible owing to the lack of room and/or safety and durability requirements. In these cases, strain piezoelectric harvesters can be adopted, which directly exploit the strain of a vibrating aeronautic component. In this research, a mathematical model of a vibrating slat is developed with the modal superposition approach and is coupled with the model of a piezo-electric patch directly bonded to the slat. The coupled model makes it possible to calculate the power generated by the strain harvester in the presence of the broad-band excitation typical of the aeronautic environment. The optimal position of the piezoelectric patch along the slat length is discussed in relation with the modes of vibration of the slat. Finally, the performance of the strain piezoelectric harvester is compared with the one of a cantilever harvester tuned to the frequency of the most excited slat mode.

A unified discretization framework, based on the concept of augmented dual grids, is proposed for devising hybrid formulations which combine the Cell Method and the Boundary Element Method for static and quasi-static electromagnetic field problems. It is shown that hybrid approaches, already proposed in literature, can be rigorously formulated within this framework. As a main outcome, a novel direct hybrid approach amenable to iterative solution is derived. Both direct and indirect hybrid approaches, applied to an axisymmetric model, are compared with a reference third-order 2D FEM solution. The effectiveness of the indirect approach, equivalent to the direct approach, is finally tested on a fully 3D benchmark with more complex topology.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. In the last 30 years several neuroprotective agents, attenuating the downstream molecular and cellular damaging events triggered by TBI, have been extensively studied. Even though many drugs have shown promising results in the pre-clinical stage, all have failed in large clinical trials. Mesenchymal stromal cells (MSCs) may offer a promising new therapeutic intervention, with preclinical data showing protection of the injured brain. We selected three of the critical aspects identified as possible causes of clinical failure: the window of opportunity for drug administration, the double-edged contribution of mechanisms to damage and recovery, and the oft-neglected role of reparative mechanisms. For each aspect, we briefly summarized the limitations of previous trials and the potential advantages of a newer approach using MSCs.

The impact of raindrops on a dry surface leads to a splashing phenomenon that dissipates a lot of energy. To improve energy collection, a novel piezoelectric raindrop energy harvester equipped with a spoonful of water was developed. The advantages and the drawbacks of this solution were analyzed with the aid of numerical simulations. A series of experimental tests were carried out in a laboratory with simulated raindrops. Experimental results showed that the negative effect of the added water mass was exceeded by the positive effects related to the impact of the raindrop on a liquid surface. Tests carried out connecting the harvester to a resistive load showed that the prototype was able to collect more energy than a simple cantilever harvester.

Piezoelectric cantilever harvesters have a large power output at their natural frequency, but in some applications the frequency of ambient vibrations is different from the harvester’s frequency and/or ambient vibrations are periodic with some harmonic components. To cope with these operating conditions harvesters with integrated trimming devices (ITDs) are proposed. Some prototypes are developed with the aid of an analytical model and tested with an impulsive method. Results show that a small trimming device can lower the main resonance frequency of a piezoelectric harvester of the same extent as a larger tip mass and, moreover, it generates at high frequency a second resonance peak. A multi-physics numerical finite element (FE) model is developed for predicting the generated power and for performing a stress-strain analysis of harvesters with ITDs. The numerical model is validated on the basis of the experimental results. Several configurations of ITDs are conceived and studied. Numerical results show that the harvesters with ITDs are able to generate relevant power at two frequencies, owing to the particular shape of the modes of vibration. The stress in the harvesters with ITDs is smaller than the stress in the harvester with a tip mass trimmed to the same frequency.