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This paper presents a continuum-molecular formulation for bi-dimensional micropolar media within the mathematical formalism of a revised peridynamic theory with oriented material points. A variational procedure is considered to derive the fundamental governing equations of the model, which postulates that material points interact through pair potentials allowing generalized pairwise actions to be derived as energy conjugates to properly defined pairwise deformation measures. While continuity of mass is assumed, constitutive laws are produced for long-range micro-interactions to reproduce the effective behavior of the material at the macro-scale. The definition of proper micromoduli functions respecting material symmetries and invariance properties allows then to obtain a non-local micropolar continuum based on pseudo-discrete kinematics, while providing a mechanism-based description of material anisotropy and coupling behaviors uncovered by classical elasticity. An analytic micro-macro moduli correspondence procedure is also established, based on the formal analogy with the constitutive tensor of centrosymmetric planar micropolar continua. As an important result of this research, we show that distinctive chiral effects of micropolar elasticity can be reproduced by introducing a directional independent pseudo-scalar pair potential, which turns out to be analytically vanishing when the rotationally invariant part of the corresponding continuum elastic tensor is invariant to mirror reflections as well. Moreover, the proposed formulation demonstrates sensitivity to elastic bending size-effect as specific property of structured materials homogenized as micropolar continua, and related to the characteristic length of their underlying microstructure. The resulting constitutive non-locality, which plays an important role in fracture problems, is conceptually separated with respect to the intrinsic non-local character of the model related to the integral nature of its governing equations, and then does not vanish when the horizon reduces to zero. The theoretical findings and the effectiveness of the model are successfully verified through illustrative examples referred to representative cases of structured materials homogenized as micropolar continua, including length-scale dependent quasi-static crack propagation as well as the mechanism-based description of the coupling between bulk strain and micro-rotation in elastic bi-dimensional homogenized chiral lattices. • Continuum-molecular formulation for bi-dimensional micropolar elasticity. • Mechanism-based description of material anisotropy and chiral properties. • All the symmetry classes of centrosymmetric 2D micropolar elasticity are covered. • Sensitivity to bending size-effect in microstructured solids is shown. • Analogies between continuum-molecular models and periodic lattice-like materials. [ABSTRACT FROM AUTHOR]

A spectro-hierarchical algorithm is proposed to determine an approximate solution to the elasto-dynamic problem for periodic heterogeneous materials. Such a homogenization scheme is derived by employing tools from perturbation theory in finite dimension used in the context of the celebrated Theorem of Nekhoroshev. In particular, it is shown how a classical algorithm based on a suitable hierarchy of harmonics can be implemented for the problem at hand, leading to the explicit construction of functions approximating the solution of the original problem with an error that is superexponentially small in the cell dimension. According to this approach, the fully homogenized model turns out to be naturally related to the "integrable case" of perturbation theory. Furthermore, all the featured constants are estimated explicitly. More importantly, a fully detailed bound of the threshold for the cell dimension is presented to ensure the validity of the theory. An example of application of the described theory is given in the final section for the case of a layered material. • The paper deals with the system of PDEs arising from elasto-dynamic problems in Cauchy materials. • Focuses on a novel approach based on perturbation theory to deal with homogenisation-type problems. • Provides an explicit scheme to approximate the solutions of the problem at hand. • Gives explicit estimates of validity of the theory. [ABSTRACT FROM AUTHOR]

A multifield asymptotic homogenization technique for periodic thermo-diffusive elastic materials is provided in the present study. Field equations for the first-order equivalent medium are derived and overall constitutive tensors are obtained in closed form. These lasts depend upon the micro constitutive properties of the different phases composing the composite material and upon periodic perturbation functions, which allow taking into account the effects of microstructural heterogeneities. Perturbation functions are determined as solutions of recursive non homogeneous cell problems emanated from the substitution of asymptotic expansions of the micro fields in powers of the microstructural characteristic size into local balance equations. Average field equations of infinite order are also provided, whose formal solution can be obtained through asymptotic expansions of the macrofields. With the aim of investigating dispersion properties of waves propagating inside the medium, proper integral transforms are applied to governing field equations of the homogenized medium. A quadratic generalized eigenvalue problem is thus obtained, whose solution characterizes the complex valued frequency spectrum of the first-order equivalent material. The validity of the proposed technique has been confirmed by the very good matching obtained between dispersion curves of the homogenized medium and the lowest frequency ones relative to the heterogeneous material. These lasts are computed from the resolution of a quadratic generalized eigenvalue problem over the periodic cell subjected to Floquet–Bloch boundary conditions. An illustrative benchmark is conducted referring to a Solid Oxide Fuel Cell (SOFC)-like material, whose microstructure can be modeled through the spatial tessellation of the domain with a periodic cell subjected to thermo-diffusive phenomena. [ABSTRACT FROM AUTHOR]

A non-local dynamic homogenization technique for the analysis of wave propagation in viscoelastic heterogeneous materials with a periodic microstructure is herein proposed. The asymptotic expansion of the micro-displacement field in the transformed Laplace domain allows obtaining, from the expression of the micro-scale field equations, a set of recursive differential problems defined over the periodic unit cell. Consequently, the cell problems are derived in terms of perturbation functions depending on the geometrical and physical-mechanical properties of the material and its microstructural heterogeneities. A down-scaling relation is formulated in a consistent form, which correlates the microscopic to the macroscopic transformed displacement field and its gradients through the perturbation functions. Average field equations of infinite order are determined by substituting the down-scaling relation into the micro-field equation. Based on a variational approach, the macroscopic field equation of a non-local continuum is delivered and the local and non-local overall constitutive and inertial tensors of the homogenized continuum are determined. The problem of wave propagation is investigated in case of a bi-phase layered material with orthotropic phases and axis of orthotropy parallel to the direction of layers as a representative example. In such a case, the local and non-local overall constitutive and inertial tensors are determined analytically. Finally, in order to test the reliability of the proposed approach, the dispersion curves obtained from the non-local homogenized model are compared with the curves provided by the Floquet-Bloch theory. [ABSTRACT FROM AUTHOR]

High dose Post transplant cyclophosphamide (PTCy) is now regarded as a very effective way of preventing acute and chronic GvHD, and it's use has rapidly expanded world-wide. [ABSTRACT FROM AUTHOR]

We report 634 patients who underwent unmanipulated haploidentical (HAPLO) bone marrow transplantation (BMT) in two Centers. The diagnosis was acute myeloid leukemia (AML) (n = 251), acute lymphoblastic leukemia (ALL)(n = 107), myelodysplastic syndrome and myelofibrosis (MDS + MF) (n = 125) and chronic lymphoproliferative disorders (n = 151). Median age was 52 years (16–74). Graft versus host disease (GvHD) prophylaxis was intravenous cyclosporin (CSA) starting on day 0, oral mycophenolate on day +1, and post-transplant cyclophosphamide (PTCY) on days +3 + 5. Primary graft failure was seen in 23 patients (3,6%); 17 /23 (74%) were rescued with second HAPLO graft, and were alive at one year. The cumulative incidence of acute GvHD grade II-IV was 29% and 3% for grade III-IV; the cumulative incidence of moderate severe chronic GvHD was 23%: older donor and patients age were significant predictors of both acute and chronic GvHD. The overall non relapse mortality (NRM) at 2 years was 19%: 8%, 21% and 30% in patients aged <40, 41–60 > 60 years. Disease free survival (DFS) at 5 years was 64% for acute leukemia in first remission, 51% for acute leukemia CR2, 25% for acute leukemia advanced disease and 49% for MDS/MPN. We confirm, on a relatively large number of patients, that unmanipulated HAPLO BMT with PTCY on days +3 + 5, mostly after a myeloablative conditioning regimen, is followed by a low incidence of graft failure and grade III-IV GvHD; moderate severe chronic GvHD is 23% and NRM at 2 years 19%; 5 year DFS is influenced by remission status of the underlying disease. [ABSTRACT FROM AUTHOR]

Post-transplant cyclophosphamide (PTCy) allows safe and effective partially matched donor allogeneic blood or marrow transplantation (alloBMT), so that almost everyone in need of the procedure now has a donor. Moreover, PTCy and other recent advances have lowered alloBMT mortality rates to less than half of that seen before the turn of the century, at costs that are substantially less than most newly approved anticancer agents. These advances also make tailoring BMT based on patients' unique diseases and characteristics now feasible for further improving outcomes. Personalizing every aspect of alloBMT, including conditioning, donor, graft type, and post-transplant maintenance is now possible. For example, alloBMT's antitumor activity historically was restricted to the allogeneic graft-versus-tumor effect directed against histocompatibility antigens. However, replacing exhausted immune systems with healthy non-exhausted, non-tolerant ones likely can enhance the activity of novel targeted therapies. The impressive results seen with tyrosine kinase inhibitors after alloBMT for patients with both Ph+ acute lymphoblastic leukemia and FLT/ITD+ acute myeloid leukemia herald the potential of precision BMT. [ABSTRACT FROM AUTHOR]

Highlights • Enhanced homogenization technique to obtain thermodynamically consistent micropolar continuum models of the beam lattices. • Micropolar continuum model provide good approximations of the static and dynamic behaviour of the Lagrangian model. • Continualization technique based on a pseudo-differential down-scaling law. • Higher order models characterized by non-local inertia terms and spatial high gradient terms. Abstract The enhanced continualization approach proposed in this paper is aimed to overcome some drawbacks observed in the homogenization of beam lattices. To this end an enhanced homogenization technique is proposed and formulated to obtain consistent micropolar continuum models of the beam lattices and able to simulate with good approximation the boundary layer effects and the Floquet–Bloch spectrum of the Lagrangian model. The continualization technique here proposed is based on a transformation of the difference equation of motion of the discrete system via a proper down-scaling law into a pseudo-differential problem; a further McLaurin approximation is applied to obtain a higher order differential problem. The formulation is carried out for simple one-dimensional beam lattices that are, nevertheless, characterized by a rather wide variety of static and dynamic behaviors: the rod lattice, the beam lattice with node rotations and a 1D beam lattice model with generalized displacements. Higher order models may be obtained which are characterized by differential problems involving non-local inertia terms together with spatial high gradient terms. Moreover, the homogenized models obtained by the proposed enhanced continualization technique turn out to be energetically consistent and provide a good simulation of both the static response and of the acoustic spectrum of the original discrete models. The proposed homogenization procedure is first presented for the simple case of monoatomic axial chains. The beam lattice with node rotations and displacement prevented exhibits, in the static regime, decaying oscillations of the nodal rotation in the boundary layer which is well simulated by the homogenized model obtained by the proposed approach. Similar good results are obtained in the simulation of the optical spectrum. It is worth to note that in this case the homogenized model obtained via Padé approximation turns out to be energetically non-consistent. The analysis of the homogenized model derived from the beam lattice with transverse displacement and rotation of the nodes with elastic supports has shown that both the static and the dynamic response are strongly variable on the parameters of the Lagrangian model. Finally, several different cases have been considered and good simulations have been obtained both in describing the static response to prescribed displacements at the end nodes and in representing the Floquet–Bloch spectrum and the polarization vectors. Graphical abstract Image, graphical abstract [ABSTRACT FROM AUTHOR]

Highlights • A multi-field asymptotic homogenization technique for thermo-piezoelectric periodic materials is performed. • A consistent and exact determination of the overall constitutive tensors of the microstructured material is provided. • Characterization of microstructured unimorph and bimorph bender actuators behavior. • The effect of the microstructure on the global deflection of the benders has been investigated. Graphical abstract Abstract The use of integrated MicroElectroMechanical systems (MEMS) is recently spread thanks to their improved sensitivity, accuracy and reliability. Accurate preliminary computations born from the need of high precision in the manufacturing process of such devices. Piezoelectric materials are broadly employed in this field as direct converters between mechanical and electrical signals and some of these piezoelectric materials show pyroelectric features, which involve thermo-electrical interactions. Pyroelectric bending actuators are analyzed in the present study in plane conditions. They consists of active PZT layers with in-plane polarization and a microstructured composite layer characterized by a periodic microstructure where PZT fibers with an out of plane polarization are immersed in a polymeric matrix. The constitutive law of the composite layer at the mesoscale has been determined by means of a multi-field asymptotic homogenization technique, recently developed for thermo-piezoelectric materials. Overall constitutive equations characterizing the behavior of the microstructured layer at the mesoscale have been derived and the closed form of the overall constitutive tensors has been provided for the equivalent first-order (Cauchy) homogenized continuum. Deflection of unimorph and bimorph bender actuators has been investigated in relation to their geometrical features, exploiting the out of plane piezoelectric properties of the composite layer, which modify the stiffness of the entire bender. An accurate description of benders behavior at the structural length scale is of fundamental importance in order to design devices with high performances. In this regard, the influence of the microstructure on the global response of the actuator is investigated in the present study in order to understand how the composite material can be tailored to meet specific design requirements. [ABSTRACT FROM AUTHOR]

The free propagation of acoustic plane waves through cellular periodic materials is generally accompanied by a flow of mechanical energy across the adjacent cells. The paper focuses on the energy transport related to dispersive waves propagating through non-dissipative microstructured materials. The generic microstructure of the periodic cell is described by a beam lattice model, suitably reduced to the minimal space of dynamic degrees-of-freedom. The linear eigenproblem governing the wave propagation is stated and the complete eigensolution is considered to study both the real-valued dispersion functions and the complex-valued waveforms of the propagating elastic waves. First, a complete family of nondimensional quantities ( polarization factors ) is proposed to quantify the linear polarization or quasi-polarization, according to a proper energetic criterion. Second, a vector variable related to the periodic cell is introduced to assess the directional flux of mechanical energy, in analogy to the Umov–Poynting vector related to the material point in solid mechanics. The physical-mathematical relation between the energy flux and the velocity of the energy transport is recognized. The formal equivalence between the energy and the group velocity is pointed out, according to the mechanical assumptions. Finally, all the theoretical developments are successfully applied to the prototypical beam lattice material characterized by a periodic tetrachiral microstructure. As case study, the tetrachiral material offers interesting examples of perfect and nearly-perfect linear polarization. Furthermore, the nonlinear dependence of the energy fluxes on the elastic waveforms is discussed with respect to the acoustic and optical surfaces featuring the energy spectrum of the material. As final remark, the occurrence of negative refraction phenomena is found to characterize the high-frequency optical surface of the frequency spectrum. [ABSTRACT FROM AUTHOR]

Tetrachiral materials are characterized by a cellular microstructure made by a periodic pattern of stiff rings and flexible ligaments. Their mechanical behaviour can be described by a planar lattice of rigid massive bodies and elastic massless beams. The periodic cell dynamics is governed by a monoatomic structural model, conveniently reduced to the only active degrees-of-freedom. The paper presents an explicit parametric description of the band structure governing the free propagation of elastic waves. By virtue of multiparametric perturbation techniques, sensitivity analyses are performed to achieve an analytical asymptotic approximation of the dispersion functions. The parametric conditions for the existence of full band gaps in the low-frequency range are established. Furthermore, the band gap amplitude is analytically assessed in the admissible parameter range. In tetrachiral acoustic metamaterials, stop bands can be opened by the introduction of intra-ring resonators. Perturbation methods can efficiently deal with the consequent enlargement of the mechanical parameter space. Indeed high-accuracy parametric approximations are achieved for the band structure, enriched by the new optical branches related to the resonator frequencies. In particular, target stop bands in the metamaterial spectrum are analytically designed through the asymptotic solution of inverse spectral problems. [ABSTRACT FROM AUTHOR]

The present paper is focused on the acoustic behaviour of periodic beam-lattices metamaterials containing inertial viscoelastic resonators connected with elastic slender ligaments. A simplified model is considered where the ligaments are considered as massless and the viscoelastic resonators are contained inside rigid rings located at the lattice nodes. Firstly, a Lagrangian model is formulated in order to assess the influence of the dynamic and viscoelastic properties of the resonators on the acoustic behaviour. An equivalent generalized micropolar model is obtained through a continualization of the discrete model and the constitutive tensors and the equation of motion are formulated. The propagation of harmonic waves is assumed and the Christoffel equation for both the discrete and the continuum model are obtained. It is shown that the hermitian matrix governing the Christoffel equation of the Lagrangian model is approximated by the corresponding one from the micropolar model with an error O (|k| 3 ) [ABSTRACT FROM AUTHOR]

Tetrachiral materials are characterized by a cellular microstructure made by a periodic pattern of stiff rings and flexible ligaments. Their mechanical behaviour can be described by a planar lattice of rigid massive bodies and elastic massless beams. Therefore, the periodic cell dynamics is governed by a monoatomic structural model, conveniently reduced to the only active degrees-of-freedom. The paper presents an explicit parametric description of the Floquet-Bloch spectrum (or band structure) governing the propagation of elastic waves through the tetrachiral material. By virtue of multiparametric perturbation techniques, an analytical asymptotic approximation is achieved for the dispersion surfaces in the Brillouin zone. Since different optimization strategies tend to fail in opening low-frequency band gaps in the material spectrum, this specific design purpose is commonly pursued by introducing interring inertial resonators. The paper demonstrates that multiparametric perturbation methods can efficiently deal with the consequent enlargement of the parameter space, necessary to describe the resulting inertial metamaterial. Indeed, paying due attention to the doubling of internal resonance conditions, an accurate parametric approximations of the enriched band structure can be achieved. From the applicative perspective, the research findings furnish suited analytical tools for the optimal design of pass and stop bands. [ABSTRACT FROM AUTHOR]

In this paper, an advanced computational method is proposed, whose aim is to obtain an approximately optimal design of a particular class of acoustic metamaterials, by means of a novel combination of multi-objective optimization and dimensionality reduction. Metamaterials are modeled as beam lattices with internal local resonators coupled with the microstructure through a viscoelastic phase. The dynamics is governed by a set of integro-differential equations, that are transformed into the Z -Laplace space in order to derive an eigenproblem whose solution provides the dispersion relation of the free in-plane propagating Bloch waves. A multi-objective optimization problem is stated, whose aim is to achieve the largest multiplicative trade-off between the bandwidth of the first stop band and the one of the successive pass band in the metamaterial frequency spectrum. Motivated by the multi-dimensionality of the design parameters space, the goal above is achieved by integrating numerical optimization with machine learning. Specifically, the problem is solved by combining a sequential linear programming algorithm with principal component analysis, exploited as a data dimensionality reduction technique and applied to a properly sampled field of gradient directions, with the aim to perform an optimized sensitivity analysis. This represents an original way of applying principal component analysis in connection with multi-objective optimization. Successful performances of the proposed optimization method and its computational savings are demonstrated. [Display omitted] • Mechanical model departs from a viscoelastic metamaterial description. • A multi-objective optimization is exploited to optimize spectral functionalities. • Data-dimensionality reduction is performed through Principal Component Analysis. • Principal Component Analysis is combined in a novel way with optimization. • Computational efficiency of the adopted optimization method is demonstrated. [ABSTRACT FROM AUTHOR]

• A novel layered metamaterial for vibration mitigation and energy absorption is proposed. • Adjacent layers consist of plane lattices having hexachiral topology with alternate chirality. • A continuum model is considered to get an effective description of the discrete system. • The metamaterial exhibits interesting bilateral, dissipative and self-recovering properties. A novel energy absorbing material is proposed for the design of shock absorbers and vibrational dampers. A layered architectured microstructure is put forward consisting of the repetition of plane lattices having hexachiral topology with alternate chirality, each being designed as a periodic assembly of rigid disks connected by elastic ligaments. Because of the chiral topology of the single layer, the rotation of the rigid disks takes place when in-plane stress states are applied so implying a relative rotation between the disks of adjacent lattices with opposite chirality. Pins passing through for each stacking of disks impose them the same in-plane displacement. Moreover, frictional dissipative mechanisms at the interface between adjacent disks according to two different compression modes orthogonal to the layers make the metamaterial suitable for either reusing or self-recovering the initial configuration. In the first case the pre-tensioning of the pins implies the compression of plane frictional interfaces. The frictional sliding compatible with the disk relative rotation implies an overall hysteretic bilinear response with remarkable energy dissipation. The metamaterial may be reused once the pins are relaxed and re-tensioned. In the latter case no pre-tension is applied to the pins and the compressive force between the disks is obtained through saw-tooth shaped interfaces between adjacent disks to get elastically constrained transverse dilation when the relative rotations at the interfaces take place. The overall response turns out to be highly dissipative and self-recovering, i.e. able to return to the initial configuration when removing the applied stresses. As shown in the examples the quasi-static behavior of the proposed metamaterial makes it a candidate as an efficient vibration damper and a shock absorber characterized by i) hysteretic response with remarkable energy dissipation under biaxial stress states; ii) reuse or self-recovering after the energy absorption event; iii) bilateral response, i.e. equal behavior under both tension and compression. [ABSTRACT FROM AUTHOR]

• 2% to 5% of healthy donors have a suboptimal stem cell mobilization. • There are no definite criteria for estimating the probability of poor mobilization. • Older age and low baseline white blood cell count affect stem cell mobilization. • A score based on age and white blood cell count predicts suboptimal mobilization. • Suboptimal mobilization score can help in the management of transplant procedure. Allogeneic peripheral blood stem cells mobilization is now the basis of most stem cell transplants. In a very limited number of cases, mobilization is suboptimal leading to further collection procedures, to suboptimal cell doses infusion with delayed engraftment time, increased risks of transplant procedure and of related costs. To date we have no recognized and shared criteria for early estimating the probability of poor mobilization in healthy donors. We then analyzed allogeneic peripheral blood stem cell donations performed at the Fondazione Policlinico Universitario A.Gemelli IRCCS Hospital from January 2013 to December 2021 in order to identify premobilization factors associated with successful mobilization. The following data were collected: age, gender, weight, complete blood cell count at baseline, G-CSF dose, number of collection procedures, CD34+ cell count in peripheral blood on the first day of collection, CD34+ cell dose per kg body weight of recipient. Mobilization efficacy was defined according to the number of CD34+ cells in peripheral blood on day +5 of G-CSF administration. We classified donors as sub-optimal mobilizers or good mobilizers according to the achievement of the 50 CD34+ cell/μL threshold. We observed 30 suboptimal mobilizations in 158 allogeneic peripheral blood stem cell donations. Age and baseline white blood cell count were factors significantly associated with negative or positive impact on mobilization, respectively. We did not find significant differences in mobilization based on gender or G-CSF dose. Using cut-off values of 43 years and 5.5×109/L WBC count, we built a suboptimal mobilization score: donors who reach 2, 1 or 0 points have a 46%, 16% or 4% probability of suboptimal mobilization, respectively. Our model explains 26% of the variability of mobilization confirming that most of the mobilization magnitude depends on genetically determined factors; however, suboptimal mobilization score is a simple tool providing an early assessment of mobilization efficacy before G-CSF administration begins in order to support allogeneic stem cells selection, mobilization and collection. Through a systematic review, we looked for confirmation of our findings. According to the published articles, all the variables we included in our model are confirmed to be strongly related to the success of mobilization. We believe that score system approach could be applied in clinical practice to assess the risk of mobilization failure at baseline allowing for a priori intervention. [ABSTRACT FROM AUTHOR]

This study proposes a multi-field asymptotic homogenization for the analysis of thermo-piezoelectric materials with periodic microstructures. The effect of the microstructural heterogeneity is taken into account by means of periodic perturbation functions, which derive from the solution of nonhomogeneous recursive cell problems defined over the unit periodic cell. A strong coupling is present between the microdisplacement field and the microelectric potential field, since the mechanical and the electric problems are fully coupled in the asymptotically expanded microscale field equations. The microdisplacement, the electric potential, and the relative temperature fields have been related to the macroscopic quantities and to their gradients in the derived down-scaling relations. Average field equations of infinite order have been obtained and the closed form of the overall constitutive tensors has been determined for the equivalent first-order homogenized continuum. A formal solution of such equations has been derived by means of an asymptotic expansion of the macrofields. The accuracy of the proposed formulation is assessed in relation to illustrative examples of a bi-material periodic microstructure subjected to harmonic body forces, free charge densities, and heat sources, whose periodicity is much greater than the characteristic microstructural size. The good agreement obtained between the solution of the homogenized model and the finite element solution of the original heterogeneous material problem confirms the validity of the proposed formulation. [ABSTRACT FROM AUTHOR]

The in-plane acoustic behavior of non-centrosymmetric lattices having nodes endowed with mass and rotational inertia and connected by massless ligaments with asymmetric elastic properties has been analyzed through a discrete model and a continuum micropolar model. In the first case the propagation of harmonic waves and the dispersion functions have been obtained by the discrete Floquet–Bloch approach. It is shown that the optical branch departs from a critical point with vanishing group velocity and is decreasing for increasing the norm of the wave vector. A micropolar continuum model has been derived through a continualization method based on a down-scaling law from a second-order Taylor expansion of the generalized macro-displacement field. It is worth noting that the second order elasticity tensor coupling curvatures and micro-couples turns out to be negative-definite also in the general case of non-centrosymmetric lattice. The eigenvalue problem governing the harmonic propagation in the micropolar non-centrosymmetric continuum results in general characterized by a hermitian full matrix that is exact up to the second order in the wave vector. Examples concerning square and equilateral triangular lattices have been analyzed and their acoustic properties have been derived with the discrete and continuum models. The dependence of the Floquet–Bloch spectra on the lattice non-centrosymmetry is shown together with validity limits of the micropolar model. Finally, in consideration of the negative definiteness of the second order elastic tensor of the micropolar model, the loss of strong hyperbolicity of the equation of motion has been investigated. [ABSTRACT FROM AUTHOR]

The elastic wave propagation is investigated in a beam lattice material characterized by a square periodic cell with anti-tetrachiral microstructure. With reference to the Floquet-Bloch spectrum, focus is made on the band structure enrichments and modifications which can be achieved by equipping the cellular microstructure with tunable local resonators. By virtue of its composite mechanical nature, the so-built inertial meta-material gains enhanced capacities of passive frequency-band filtering. Indeed the number, placement and properties of the inertial resonators can be designed to open, shift and enlarge the band gaps between one or more pairs of consecutive branches in the frequency spectrum. In order to improve the meta-material performance, several nonlinear optimization problems are formulated. The largest among the band gap amplitudes in the low-frequency range is selected as suited objective function. Proper inequality constraints are introduced to restrict the admissible solutions within a compact set of mechanical and geometric parameters, including only physically realistic properties of both the lattice and the resonators. The optimization problems related to full and partial band gaps are solved by using a globally convergent version of the numerical method of moving asymptotes, combined with a quasi-Monte Carlo multi-start technique. The optimal solutions are numerically computed, discussed and compared from the qualitative and quantitative viewpoints, bringing to light the limits and potential of the meta-material performance. The clearest trends emerging from the numerical analyses are pointed out and interpreted from the physical viewpoint. Finally, some specific recommendations about the microstructural design of the meta-material are synthesized. [ABSTRACT FROM AUTHOR]

Lattice-like materials featuring periodic planar tessellation of regular rigid blocks connected by linear elastic interfaces and chiral or achiral properties are considered. The chirality results from a uniform rotation of the blocks with respect to their centroidal joining line and leads to interesting auxetic and dispersive acoustic behaviors. The governing equations of the discrete Lagrangian model are properly manipulated via the novel enhanced continualization scheme in such a way to obtain equivalent non-local integral and gradient-type higher-order continua. Based on the formal Taylor series expansion of the integral kernels or the corresponding pseudo-differential functions accounting for shift operators and proper pseudo-differential downscaling laws, the proposed enhanced continualization technique allows formulating homogeneous non-local continuum models of increasing orders, analytically featured by characteristic non-local constitutive and inertial terms. The enhanced continualization shows thermodynamic consistency in the definition of the overall non-local constitutive tensors, as well as qualitative agreement and quantitative convergent matching of the actual complex frequency band structure. The theoretical findings are successfully verified though the study of wave dispersion and attenuation properties as referred to a representative tetrachiral geometry. • An enhanced dynamic continualization scheme for block-lattices is proposed. • Identification of non-local integral-type and gradient-type higher order continua. • Thermodynamically-consistent constitutive laws are obtained. • Dispersive Bloch-wave propagation in tetrachiral material is analyzed. [ABSTRACT FROM AUTHOR]

The class of anti-tetrachiral cellular materials is phenomenologically characterized by a strong auxeticity of the elastic macroscopic response. The auxetic behavior is activated by rolling-up deformation mechanisms developed by the material microstructure, composed by a periodic pattern of stiff rings connected by flexible ligaments. A linear beam lattice model is formulated to describe the free dynamic response of the periodic cell, in the absence of a soft matrix. After a static condensation of the passive degrees-of-freedom, a general procedure is applied to analyze the wave propagation in the low-dimensional space of the active degrees-of-freedom. The exact dispersion functions are compared with explicit – although approximate – dispersion relations, obtained from asymptotic perturbation solutions of the eigenproblem governing the Floquet–Bloch theory. A general hierarchical scheme is outlined to formulate and solve the perturbation equations, taking into account the dimension of the perturbation vector. Original recursive formulas are presented to achieve any desired order of asymptotic approximation. For the anti-tetrachiral material, the fourth-order asymptotic solutions are found to approximate the dispersion curves with fine agreement over wide regions of the parameter space. The asymptotic eigensolutions allow an accurate sensitivity analysis of the material spectrum under variation of the key physical parameters, including the cell aspect ratio, the ligament slenderness and the spatial ring density. Finally, the explicit dependence of the dispersion functions on the mechanical parameters may facilitate the custom design of specific spectral properties, such as the wave velocities and band gap amplitudes. [ABSTRACT FROM AUTHOR]

Magneto-electro-elastic (MEE) materials are attracting an increasing amount of scientific interest in physics, for their valuable potential in the functional management of mechanical-to-magnetoelectric energy conversions. The present paper focuses on heterogeneous MEE media – artfully realized by virtue of the periodic repetition of a multi-phase elementary cell – which represent promising solutions to passively control the propagation of multifield Bloch waves. Specifically, the linear continuum model governing the coupled free dynamics of a cellular non-dissipative MEE material is formulated for the unbounded three-dimensional domain. Then, the governing equations are specialized for a periodic layered waveguide with perfect inter-layer interfaces. The Floquet–Bloch decomposition is employed to analytically determine the uni-modular transfer matrix of the heterogeneous multi-layered cell. The related eigenproblem, governed by a palindromic characteristic polynomial in the Floquet multipliers, is solved in closed form to analyze the dispersion properties in the real-valued frequency domain and complex-valued wavenumber domain. Alternatively, a perturbation scheme is outlined to asymptotically approximate the exact eigensolutions. The dispersion spectra, composed of propagation and attenuation branches, are parametrically investigated for a two-layered periodic waveguide. The corresponding band structures are assessable a priori by leveraging the formal analogy with the stability analysis for non-autonomous dynamical systems. As main findings, slow-propagating quasi-shear-elastic waves and fast-propagating quasi-magneto-electric waves are found to dominate the low-frequency and high-frequency ranges, respectively, although some crossing points between the respective spectral branches can be detected. Quantitatively different but qualitatively similar behaviors of propagation and/or attenuation are observed for the quasi-shear-elastic waves and quasi-magneto-electric waves. Consequently, pass–pass, pass–stop and stop–stop bands of frequencies can be recognized and tuned by varying the key physical parameters. This rich spectral scenario opens the way for the functional customization of MEE-based metafilters or metapropagators, purposely designed to govern the transfer, localization, conversion, harvesting of energy across large frequency ranges. • Free wave propagation through a periodic non-dissipative MEE material is studied • The dispersion properties of periodic layered waveguide are analytically derived • Floquet multipliers are derived by solving the palindromic characteristic polynomial • Perturbation scheme is outlined to asymptotically approximate the eigensolutions • Pass–pass, pass–stop and stop–stop bands of frequencies can be recognized and tuned [Display omitted] [ABSTRACT FROM AUTHOR]

A simplified model of periodic chiral beam-lattices containing local resonators has been formulated to obtain a better understanding of the influence of the chirality and of the dynamic characteristics of the local resonators on the acoustic behaviour. The beam-lattice models are made up of a periodic array of rigid heavy rings, each one connected to the others through elastic slender massless ligaments and containing an internal resonator made of a rigid disk in a soft elastic annulus. The band structure and the occurrence of low frequency band-gaps are analysed through a discrete Lagrangian model. For both the hexa- and the tetrachiral lattice, two acoustic modes and four optical modes are identified and the influence of the dynamic characteristics of the resonator on those branches is analysed together with some properties of the band structure. By approximating the ring displacements of the discrete Lagrangian model as a continuum field and through an application of the generalized macro-homogeneity condition, a generalized micropolar equivalent continuum has been derived, together with the overall equation of motion and the constitutive equation given in closed form. The validity limits of the dispersion functions provided by the micropolar model are assessed by a comparison with those obtained by the discrete model. [ABSTRACT FROM AUTHOR]

A comprehensive characterization of the novel class of anti-tetrachiral cellular solids, both considering the static and the dynamic response, is provided in the paper. The heterogeneous material is characterized by a periodic microstructure made of equi-spaced rings each interconnected by four ligaments. In the most general case, rings and ligaments are surrounded by a softer matrix and the rings can be filled by a different material. First, the first order linear elastic homogenized constitutive response is estimated resorting to two different microstructural models: a discrete model, in which the ligaments are modeled as beams and the presence of the matrix is neglected and the equivalent elastic properties are evaluated through a simplified analytical approach, and a more detailed continuous model, where the actual properties of matrix, ligaments and rings, varying in the 2D domain, are considered and the first order computational homogenization is adopted. Special attention is given to the dependence of the 2D overall Cauchy-type elastic constants on the mechanical and geometrical parameters characterizing the microstructure. The results, indeed, show the existence of large variations in the linear elastic constants and degree of anisotropy. A comparison with available experimental results confirms the validity of the analytical and numerical approaches adopted. Finally, the rigorous Floquet–Bloch approach is applied to the periodic cell of the cellular solid to evaluate the dispersion of propagation waves along the orthotropic axes in the framework of elasticity and to detect band gaps characterizing the material. A numerical approach, based on the first order computational homogenization, is also adopted and the rigorous and approximate solutions are compared. [ABSTRACT FROM AUTHOR]

Mechanical metamaterials composed of a non dissipative periodic microstructure of flexible ligaments and stiff rings, viscoelastically coupled with local resonators, are considered. By following a variational approach, the linear damped dynamics are described according to a beam lattice formulation, valid for a generic coordination number. A consistent theoretical description of the viscoelastic ring-resonator coupling is introduced, leading to an integral–differential form of the governing equations. The enlargement of the model dimension by addition of viscoelastic states allows to conveniently describe the metamaterial dynamics through a system of ordinary differential equations. Therefore, the application of the Z -transform and a suitable mapping in the wavevector space allows to obtain the system of ordinary differential equations governing the free and forced propagation of damped waves. Subsequently, the polynomial eigenproblem ruling the harmonic free wave propagation in the complex frequency domain is stated by applying the bilateral Laplace transform, whereas an analytical procedure is outlined to solve the forced wave propagation problem in the time domain. The triangular beam lattice metamaterial is considered as significant benchmark for application of the theoretical and methodological framework. Considering first the free wave propagation, the properties of the dynamic stiffness matrix are discussed and the dispersion frequency spectrum is parametrically investigated, with focus on the spectral effects of the viscoelastic coupling. The dependence of the stop bandwidth amplitude between the low and high-frequency spectral branches on the relaxation time characterizing the viscous function is also highlighted and discussed. Moreover, the forced response to a harmonic external point source is numerically investigated in the time domain. The results are qualitatively compared and quantitatively discussed by distinguishing the fundamental cases of non-resonant, resonant and quasi-resonant excitation frequency. [Display omitted] • Mechanical metamaterials are modeled as beam lattices with damped local resonators. • Integral–differential viscoelastic laws are expressed by added dynamic states. • Free and forced wave propagation is investigated in the frequency and time domains. • Complex dispersion spectra are determined for triangular beam lattice metamaterials. • Forced responses are analyzed for non-resonant and resonant excitation frequencies. [ABSTRACT FROM AUTHOR]

A novel class of Fibonacci-based high performance tunable hierarchical waveguides is here proposed and special focus is devoted to the design of adaptive-passive control systems for the Bloch wave propagation. By exploiting the features of periodic approximants, the metamaterial is conceived by the proper repetition of an elementary cell along a fixed direction. This elementary cell is made up of two building blocks repeated according to the Fibonacci sequence, to form a quasi-periodic finite microstructured system The former building block is made of a homogeneous elastic material, while the latter is a microstructured two-phase laminate. One of these phases is piezoelectric shunted by a suitably conceived electrical circuit, such that the constitutive properties of the piezoelectric phase are tuned by adjusting its equivalent impedance/admittance. Moreover, the overall constitutive properties of the microstructured layer are determined, exploiting the scale separation, via an asymptotic homogenization scheme. Then, it is possible to determine the frequency band structure of the tunable waveguide by exploiting the transfer matrix approach. With the aim of providing broad design directions, attention is paid to characterizing the dispersion waves properties of the tunable Fibonacci-like superlattices described by several generations of the Fibonacci sequence and for different values of the orientation angle of the two-phase laminate. [Display omitted] • New hierarchical waveguides are designed via tunable Fibonacci-like superlattices. • Different Fibonacci generations of the metamaterial are investigated. • Mechanical properties are tuned using a piezoelectric shunting phase. • The characterization gives useful information for optimal design of acoustic filters. [ABSTRACT FROM AUTHOR]

The present work proposes a variational-asymptotic homogenization technique for non-conventional thermo-viscoelastic periodic microstructured materials. According to second sound theories, the heat flux vector linearly depends upon the history of temperature gradient and the heat conduction tensor represents the kernel of the relative hereditary integral, thus overcoming the paradox inferred from the usual Fourier's law of thermal waves propagating at infinite speed. Down-scaling relations have been provided in the frequency domain, relating the transformed micro displacement and relative temperature fields to the corresponding macro variables and their gradients through frequency-dependent perturbation functions which convey the influence of the underlying microstructural heterogeneity. Average field equations of infinite order have been derived. Transformed field equations of the equivalent first-order medium have been obtained as Euler–Lagrange equations of a suitable functional whose first variation is properly truncated. They are characterized by frequency-dependent overall constitutive tensors, whose closed form has been provided. A benchmark test assesses the capabilities of the proposed homogenization method, where the solutions relative to a periodic, bi-phase, thermo-viscoelastic material and to the equivalent homogenized medium match under the hypothesis of periodic source terms. [Display omitted] • Homogenization scheme for non conventional thermo-viscoelastic materials. • Second sound theories are taken into account in the heat flux constitutive law. • Macro-field equations are obtained as Euler–Lagrange equations of power-like functional. • Frequency-dependent overall constitutive tensors have been determined. • Benchmark tests of a multi-field bi-phase periodic medium are performed. [ABSTRACT FROM AUTHOR]

The homogenization of periodic hexachiral and tetrachiral honeycombs is dealt with two different techniques. The first is based on a micropolar homogenization. The second approach, developed to analyse two-dimensional periodic cells consisting of deformable portions such as the ring, the ligaments and possibly a filling material, is based on a second gradient homogenization developed by the authors. The obtained elastic moduli depend on the parameter of chirality, namely the angle of inclination of the ligaments with respect to the grid of lines connecting the centers of the rings. For hexachiral cells the auxetic property of the lattice together with the elastic coupling modulus between the normal and the asymmetric strains is obtained; a property that has been confirmed here for the tetrachiral lattice. Unlike the hexagonal lattice, the classical constitutive equations of the tetragonal lattice turns out to be characterized by the coupling between the normal and shear strains through an elastic modulus that is an odd function of the parameter of chirality. Moreover, this lattice is found to exhibit a remarkable variability of the Young’s modulus and of the Poisson’s ratio with the direction of the applied uniaxial stress. Finally, a simulation of experimental results is carried out. [ABSTRACT FROM AUTHOR]

Highlights: [•] Patients undergoing haematopoietic stem-cell transplantation (HSCT) were studied. [•] Alveolar–capillary membrane diffusing capacity (D M,CO) and pulmonary capillary volume (V C) were calculated. [•] Before HSCT, D M,CO was ∼40% less than in healthy controls while V C was not different. [•] After HSCT, D M,CO further decreased by ∼22% while V C did not change. [•] Lung density, serum reactive oxygen metabolites and C-reactive protein increased after HSCT. [Copyright &y& Elsevier]

Cord blood transplant (CBT) in adult patients is scarcely utilized because of the risk of graft failure or very delayed platelet recovery. To improve the capacity and the speed to engraft, we have developed an intra-bone (IB) cord blood transplant technique. 75 patients with hematological malignancies, categorized by disease phase as early (18%), intermediate (20%) and advanced (62%), were transplanted. The median cell dose (TNC) infused was: 2.6 (1.35–5.4)×107/kg; the HLA disparity was: 12 cases=5/6, 62 cases=4/6 and 1 case=3/6 matched antigens. 72/75 patients engrafted (96%); median day of recovery of neutrophils (PMN) >500×109/L and platelets (PLT) >20 000×109/L was: 23 (14–44) and 35 (16–70) days respectively. The outcomes at 2 years according to Kaplan–Meier are: OS=46%±5; RI=18%±2; NRM=39%±5. Acute GVHD incidence/severity was: grade 0–I=64%, II=14%, III–IV=0%. The incidence of Chronic GVHD was globally low but in 3 cases was very severe. Intra-bone CBT is associated with high rate of engraftment, early and robust platelet recovery, low incidence of acute GVHD. A very promising aspect is that the relapse rate is low considering the advanced phase of the disease in two/thirds of patients. A suitable CBU was found for nearly every patient searching for a CBU. Therefore, IB CBT extends the possibility to transplant any patient for whom this approach represents the sole possibility of long-term survival. [Copyright &y& Elsevier]

Defining conditioning regimen intensity has become a critical issue for the hemopoietic stem cell transplant (HSCT) community. In the present report we propose to define conditioning regimens in 3 categories: (1) myeloablative (MA) conditioning, (2) reduced-intensity conditioning (RIC), and (3) nonmyeloablative (NMA) conditioning. Assignment to these categories is based on the duration of cytopenia and on the requirement for stem cell (SC) support: MA regimens cause irreversible cytopenia and SC support is mandatory. NMA regimens cause minimal cytopenia, and can be given also without SC support. RIC regimens do not fit criteria for MA or NMA regimens: they cause cytopenia of variable duration, and should be given with stem cell support, although cytopenia may not be irreversible. This report also assigns commonly used regimens to one of these categories, based upon the agents, dose, or combinations. Standardized classification of conditioning regimen intensities will allow comparison across studies and interpretation of study results. [Copyright &y& Elsevier]

Abstract: Matching for HLA class I alleles, including HLA-C, is an important criterion for outcome of unrelated donor transplantation. However, haplotype-mismatched transplantations for myeloid malignancies, mismatched for killer immunoglobulin-like receptor (KIR) ligands in the graft-versus-host (GVH) direction, is associated with lower rates of graft-versus-host disease (GVHD), relapse, and mortality. This study investigated the effect of KIR ligand mismatching on the outcome of unrelated donor transplantation. The outcomes after 1571 unrelated donor transplantations for myeloid malignancies where donor–recipient pairs were HLA-A, -B, -C, and -DRB1 matched (n = 1004), GVH KIR ligand–mismatched (n = 137), host-versus-graft (HVG) KIR ligand–mismatched (n = 170), and HLA-B and/or –C–mismatched but KIR ligand–matched (n = 260) were compared using Cox regression models. Treatment-related mortality (TRM), treatment failure, and overall mortality were lowest after matched transplantations. Patients who received grafts from donors mismatched at the KIR ligand in the GVH or HVG direction and mismatched at HLA-B and/or C but matched at the KIR ligand had similar rates of TRM, treatment failure, and overall mortality. There were no differences in leukemia recurrence between the 4 groups. These results do not support the choice of an unrelated donor on the basis of KIR ligand mismatch determined from HLA typing. [Copyright &y& Elsevier]

Abstract: This is an update of a randomized study on antithymocyte globulin (ATG; Thymoglobulin) before transplantation in patients undergoing unmanipulated marrow transplantation from unrelated donors. The median follow-up for surviving patients is 5.7 years. At last follow-up, chronic graft-versus-host disease (GVHD) was scored in 60% of non-ATG and in 37% of ATG patients (P = .05), and extensive chronic GVHD was present in 41% and 15%, respectively (P = .01). Chronic lung dysfunction was diagnosed in 51% versus 19% of patients (P = .005). Forced vital capacity decreased significantly with time in non-ATG patients (P = .005), but not in patients who received ATG (P = .30). The proportion of patients with Karnofsky scores of ≥90% at 4 years was 57% versus 89% in non-ATG versus ATG patients (P = .03). The actuarial 6-year survival for all patients randomized was 31% versus 44% (non-ATG versus ATG; P = .80). The cumulative incidence of transplant-related mortality was 51% versus 41% (P = .70) and of relapse was 32% versus 40% (P = .90). For patients who survived 1 year, transplant-related mortality was 25% versus 3% (P = .03), and actuarial survival was 58% versus 85% (P = .09). In conclusion, the addition of ATG to cyclosporine/methotrexate provides significant protection against extensive chronic GVHD and chronic lung dysfunction, reduces late transplant mortality, and improves quality of life in patients undergoing unrelated donor transplantation. [Copyright &y& Elsevier]

Objective: To compare the suppressive effect of mesenchymal stem cells (MSC), derived from normal individuals or severe aplastic anemia patients (SAA), on T-cell activation. Patients and Methods: We studied bone marrow MSC from 19 healthy donors and 23 SAA patients in different phases of the disease: at diagnosis (n=3), following immunosuppressive therapy (IS) (n=16), or after a bone marrow transplant (BMT) (n=4). MSC were tested for T-cell suppression in the following assays: mixed lymphocyte reaction (MLR), phytohemaglutinin (PHA)-primed cultures, activation surface markers, γ-IFN production, hematopoietic colony formation (CFC), production of cyclic ADP–ribose (cADPR). Results: The abnormalities of SAA MSC included: 1) significantly lower suppression of T-cell proliferation induced by alloantigens (p =0.009) or PHA (p =0.006); 2) impaired capacity to suppress CD38 expression on PHA-primed T cells (p =0.001); 3) impaired ability to suppress γ-IFN production in PHA cultures, resulting in an 11-fold higher γ-IFN concentration; 4) no preventive effect on T cell–mediated inhibition of CFC; and 5) significantly reduced (p =0.009) production of cADPR, a universal calcium mobilizer. MSC-mediated suppression of PHA-induced T-cell proliferation was restored to control levels in 3 of 4 patients post-BMT. Conclusion: The ability of MSC to downregulate T-cell priming, proliferation, and cytokine release is deficient in patients with SAA, persists indefinitely after immunosuppressive therapy, but seems to be restored after BMT. Whether these abnormalities are relevant to the pathogenesis of aplastic anemia remains to be determined. [Copyright &y& Elsevier]

The main purpose of the present paper is to solve the thermodynamic inconsistencies that result when deriving equivalent micropolar and/or higher order micropolar models of periodic beam-lattice materials through standard continualization schemes which provide a non-positive defined elastic potential energy. Despite this, such models are capable of accurately simulating the optical branches of the discrete Lagrangian model, a property lacking in the thermodynamically consistent standard micropolar continuum. To overcome these energetic inconsistencies while preserving good simulations of the frequency band structure, a dynamic high-frequency consistent continualization is proposed. This continualization scheme is based on a first order regularization approach coupled with a suitable transformation of the difference equation of motion of the discrete Lagrangian system into pseudo-differential equations. A formal Taylor expansion of the pseudo-differential operators allows to obtain differential field equations at various orders according to the continualization order. Thermodynamically consistent higher order micropolar continua having non-local positive defined elastic and kinetic energy are obtained. Finally, the convergence of the frequency band structure of the higher order micropolar models to that of the discrete Lagrangian system is shown as the continualization order increases. [ABSTRACT FROM AUTHOR]

It is well known that the classical energetically consistent micropolar model has limits in simulating the frequency band structure of packed granular materials (see Merkel et al., 2011). It is here shown that if a standard continualization of the difference equation of motion of the discrete model is carried out, an equivalent micropolar continuum is obtained which is able to accurately simulate the optical branches of the discrete model. Nevertheless, this homogenized continuum presents non-positive defined elastic potential energy, a deficiency that limits the reliability of the model and implies instability phenomena (destabilizing effects) in the acoustic branches. This drawback is circumvented here through an high-frequency dynamic homogenization scheme which is based on an enhanced continualization of the discrete governing equations into pseudo-differential equations. Through a formal Taylor expansion of the pseudo-differential operators a higher order differential equation corresponding to the governing equation of a non-local continuum thermodynamically consistent are obtained. The resulting approach allows obtaining an equivalent micropolar continuum characterized by inertial non-locality. Moreover, higher order continua with non-local constitutive and inertial terms may be derived. The proposed continuum models are proved to be able to accurately describe both the static and dynamic behavior of the discrete granular model. Finally, the convergence to the response of the discrete system is shown when increasing the order of the higher order continuum. [ABSTRACT FROM AUTHOR]

• Asymptotic homogenization of thermoelasticity theory with one relaxation time. • Elastic, thermal dilatation and heat conduction overall constitutive tensors. • Multiphase materials with a periodic microstructure. • Dispersion functions benchmark between the homogenized and the heterogeneous one. [Display omitted] A multi-scale variational-asymptotic homogenization method for periodic microstructured materials in presence of thermoelasticity with periodic spatially dependent one relaxation time is introduced. The asymptotic expansions of the micro-displacement and the micro-temperature fields are rewritten on the transformed Laplace space and expressed as power series of the microstructural length scale, leading to a set of recursive differential problems over the periodic unit cell. The solution of such cell problems leads to the perturbation functions. Up-scaling and down-scaling relations are then defined, and the latter allow expressing the microscopic fields in terms of the macroscopic ones and their gradients. The variational-asymptotic scheme to establish an equivalence between the equations at macro-scale and micro-scale is developed. Average field equations of infinite order are also derived. The efficiency of the proposed technique was tested in relation to a bi-dimensional orthotropic layered body with orthotropy axis parallel to the direction of the layers, where the mechanical and temperature constitutive properties were well established. The dispersion curves of the homogenized medium, truncated at the first order are compared with the dispersion curves of the heterogeneous continuum obtained by the Floquet-Bloch theory. The results obtained with the two different approaches show a very good agreement. [ABSTRACT FROM AUTHOR]

• Masonry-like periodic systems can be modelled as equivalent homogenized continua. • Standard continualization schemes can exhibit pathological mechanical behaviours. • A thermodynamically consistent model is formulated via enhanced continualization. • Accurate approximations of both the static and dynamic responses are achieved. • Increasing accuracy and convergence are obtained for higher continualization orders. Masonry-like systems composed by modular stiff units bonded by soft connections represent an efficient, versatile and ultimately successful strategy for natural and artificial macro-scale architectures. The static and dynamic behavior of masonry-like materials characterized by a running bond periodic pattern of rigid rectangular blocks and elastic interfaces is described by formulating equivalent nonlocal continuum models. The paper discusses the thermodynamic restrictions limiting the consistency of the standard continualization strategies. The inherent pathologies recognized in the macroscopic quasi-static response and/or in the dynamic dispersion properties of different continuum models motivate the original proposal of an enhanced continualization strategy. Based on the series expansion of the pseudo-differential functions accounting for shift operators and proper downscaling laws, the enhanced continualization scheme allows formulating homogeneous non-local continuum models of increasing orders, analytically featured by characteristic non-local constitutive and inertial terms. The enhanced continualization shows thermodynamic consistency in the definition of the overall elastic moduli, as well as qualitative agreement and convergent matching of the frequency dispersion functions. The theoretical findings are successfully verified though the solution of representative static and dynamic benchmark problems. [Display omitted] [ABSTRACT FROM AUTHOR]

Bone marrow transplantation is a major therapeutic option for patients with acquired severe aplastic anaemia: improved survival has been achieved in younger patients, thanks to better donor selection, conditioning regimens and graft versus host disease prophylaxis, together with improved supportive care, including diagnosis and treatment of opportunistic infections. This has not been the case for older patients over the age of 40 years. We will discuss transplantation platforms as used for different donor types and we will analyse major breakthroughs of the last years: the combination of Fludarabine and cyclophosphamide as a conditioning regimen, the use of alternative donors including HLA haploidentical related donors and new strategies to prevent acute and chronic graft versus host disease, including post transplantation Cyclophosphamide. These changes extend the option of a bone marrow transplantation for patients who lack an HLA matched donor and appear to improve engraftment and reduce graft versus host disease: whether this will be true for all age groups is currently being investigated. [ABSTRACT FROM AUTHOR]

• The periodic material microstructure characterizes the propagation of elastic waves. • Dispersive waves can be passively controlled by local viscoelastic resonators. • Integro-differential equations govern the damped wave propagation. • The viscoelasticity determines a complex-valued dispersion spectra. • Laurent series approximations of the viscoelastic coefficients are convergent. • Forced response to point excitation is investigated in time and frequency domain. Beam lattice materials are characterized by a periodic microstructure realizing a geometrically regular pattern of elementary cells. The dispersion properties governing the free dynamic propagation of elastic waves can be studied by formulating parametric discrete models of the cellular microstructure and applying the Floquet-Bloch theory. Within this framework, governing the wave propagation by means of spectral design techniques and/or energy dissipation mechanisms is a major issue of theoretical and applied interest. Specifically, the wave propagation can be inhibited by purposely designing the microstructural parameters to open stop bands in the material spectrum at target center frequencies. Based on these motivations, a general dynamic formulation is presented for determining the dispersion properties of mechanical metamaterials, modeled as locally resonant beam lattices with generic coordination number. The mechanism of local resonance is realized by tuning periodic auxiliary oscillators, viscoelastically coupled with the beam lattice microstructure. As peculiar aspect, the viscoelastic coupling is derived by a mechanical formulation based on the Boltzmann superposition integral, whose kernel is approximated by a Prony series. Consequently, the free propagation of damped waves is governed by a linear homogeneous system of integro-differential equations of motion. Therefore, differential equations of motion with frequency-dependent viscoelastic coefficients are obtained by applying the in-space Z -transform and in-time bilateral Laplace transform. The complex-valued branches characterizing the dispersion spectrum are determined and parametrically analyzed for the beam lattice characterized by quadrilateral periodic cell. The spectral branches may exceed the model dimension, due to the occurrence of pure-damping spectral components. Particularly, the spectra corresponding to Laurent series approximations of the viscoelastic coefficients are investigated and the solution admissibility and convergence for increasing order series is analyzed. The standard dynamic equations with linear viscous damping are recovered at the first-order approximation. Low-order approximations are found to underestimate the real and imaginary parts of the spectrum, as well as the low-frequency stop bandwidth. Finally, the forced response to a harmonic mono-frequent external point excitation is investigated. The metamaterial responses to non-resonant, resonant and quasi-resonant external forces are compared and discussed from a qualitative and quantitative viewpoint. [ABSTRACT FROM AUTHOR]