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Thrombus fragmentation during endovascular stroke treatment, such as mechanical thrombectomy, leads to downstream emboli, resulting in poor clinical outcomes. Clinical studies suggest that fragmentation risk is dependent on clot composition. This current study presents the first experimental characterization of the composition-dependent fracture properties of blood clots, in addition to the development of a predictive model for blood clot fragmentation. A bespoke experimental test-rig and compact tension specimen fabrication has been developed to measure fracture toughness of thrombus material. Fracture tests are performed on three physiologically relevant clot compositions: a high-fibrin clot made from a 5% haematocrit (H) blood mixture, a medium-fibrin clot made form a 20% H blood mixture, a low-fibrin clot made from a 40% H blood mixture. Fracture toughness is observed to significantly increase with increasing fibrin content, i.e. red blood cell-rich clots are more prone to tear during loading compared to the fibrin-rich clots. Results also reveal that the mechanical behaviour of clot analogues is significantly different in compression and tension. Finite element cohesive zone modelling of clot fracture experiments show that fibrin fibres become highly aligned in the direction perpendicular to crack propagation, providing a significant toughening mechanism. The results presented in this study provide the first characterization of the composition-dependent fracture behaviour of blood clots and are of key importance for development of next-generation thrombectomy devices and clinical strategies. This study provides a characterisation of the composition-dependent fracture toughness of blood clots. This entails the development of novel experimental techniques for fabrication and testing of blood clot compact tension fracture specimens. The study also develops cohesive zone models of fracture initiation and propagation in blood clots. Results reveal that the fracture resistance of fibrin-rich clots is significantly higher than red blood cell rich clots. Simulations also reveal that stretching and realignment of the fibrin network should be included in blood clot material models in order to accurately replicate compression-tension asymmetry and fibrin enhanced fracture toughness. The results of this study have potentially important clinical implications in terms of clot fracture risk and secondary embolization during mechanical thrombectomy procedures. [Display omitted] [ABSTRACT FROM AUTHOR]

The current study presents the development and implementation of a bespoke experimental technique to generate and characterise mode II crack initiation and propagation in arterial tissue. The current study begins with a demonstration that lap-shear testing of arterial tissue results in mixed mode fracture, rather than mode II. We perform a detailed computational design of a bespoke experimental method (which we refer to as a shear fracture ring test (SFRT)) to robustly and repeatably generate mode II crack initiation and propagation in arteries. This method is based on generating a localised region of high shear adjacent to a cylindrical loading bar. Placement of a radial notch in this region of high shear stress is predicted to result in a kinking of the crack during a mode II initiation and propagation of the crack over a long distance in the circumferential (c)- direction along the circumferential-axial (c-a) plane. Fabrication and experimental implementation of the SFRT on excised ovine aorta specimens confirms that the bespoke test method results in pure mode II initiation and propagation. We demonstrate that the mode II fracture strength along the c-a plane is eight times higher than the corresponding mode I strength determined from a standard peel test. We also calibrate the mode II fracture energy based on our measurement of crack propagation rates. The mechanisms of fracture uncovered in the current study, along with our quantification of mode II fracture properties have significant implications for current understanding of the biomechanical conditions underlying aortic dissection. Image, graphical abstract [ABSTRACT FROM AUTHOR]

This paper presents a methodology to establish a process structure property (PSP) relationship for the additive manufacturing (AM) of thin AISI 316L struts, as might be used in coronary stent applications. The methodology is based on a new geometrically based process-structure method for AM process variables, and crystal plasticity finite element (CPFE) modelling that includes the representation of melt pool microstructure morphology and texture. The effects of AM process variables are characterised with respect to ductility, yield strength and UTS across a range of process variables, including hatch spacing, layer thickness and build orientation (two orientations are considered: horizontal and vertical). The CPFE-predicted effect of build orientation is shown to be consistent with experimental test results. The present methodology has allowed identification of optimal hatch spacing and layer thickness for a given laser spot size, power and scanning speed. CPFE modelling of AM melt pool texture is shown to be key to successful prediction of the effects of process variables on mechanical behaviour. • New geometrically-based melt pool texture model for PBF of 316L thin struts • Crystal plasticity modelling of texture effects for orientation-dependent response • Key role of melt pool grain texture in capturing test data • Small number of grains across strut load-carrying section detrimental to ductility • Vertically-built struts show better ductility (key for stents) compared to horizontally-built struts [ABSTRACT FROM AUTHOR]

Objective: To determine if urodynamic findings other than high-pressure voiding influence the decision to perform a transurethral resection of prostate (TURP).Methods: Four clinical scenarios were created featuring a healthy 65-year-old man. An electronic survey was distributed to members of the International Continence Society and the Society for Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction.Results: Eighty-six urologists responded (median age was 45-54 years, 62% described their practice as academic). Scenario 1: an incidental residual urine >1 L with detrusor underactivity. The majority (76%) would offer a TURP; however, the estimated chance that the residual volume would improve was only 57%. Scenario 2: retention with detrusor overactivity but no voluntary voiding contraction. The majority (72%) would offer a TURP; however, the average chance quoted that he would void was only 48%. Scenario 3: catheter-dependent retention and an underactive detrusor. The majority (89%) would offer a TURP; however, the average chance quoted that he would void was only 53%. Scenario 4: a man with only frequency and urgency, but urodynamic bladder outlet obstruction. The majority (90%) would offer him a TURP; however, the average chance that his frequency and urgency would improve was only 64%, and the average estimated postoperative risk of urgency incontinence was 33%. Willingness to offer TURP did not correlate with physician characteristics.Conclusion: Urodynamic findings other than bladder outlet obstruction were associated with modest perceived outcomes after TURP; however, despite this, urologists are still willing to offer this intervention. [ABSTRACT FROM AUTHOR]

Orthopaedic devices using unidirectional carbon fibre reinforced poly-ether-ether-ketone (PEEK) laminates potentially offer several benefits over metallic implants including: anisotropic material properties; radiolucency and strength to weight ratio. However, despite FDA clearance of PEEK-OPTIMA™ Ultra-Reinforced, no investigation of the mechanical properties or failure mechanisms of a medical grade unidirectional laminate material has been published to date, thus hindering the development of first-generation laminated orthopaedic devices. This study presents the first investigation of the mechanical behaviour and failure mechanisms of PEEK-OPTIMA™ Ultra-Reinforced. The following multi-axial suite of experimental tests are presented: 0° and 90° tension and compression, in-plane shear, mode I and mode II fracture toughness, compression of ±45° laminates and flexure of 0°, 90° and ±45° laminates. Three damage mechanisms are uncovered: (1) inter-laminar delamination, (2) intra-laminar cracking and (3) anisotropic plasticity. A computational damage and failure model that incorporates all three damage mechanisms is developed. The model accurately predicts the complex multi-mode failure mechanisms observed experimentally. The ability of a model to predict diverse damage mechanisms under multiple loading directions conditions is critical for the safe design of fibre reinforced laminated orthopaedic devices subjected to complex physiological loading conditions. [ABSTRACT FROM AUTHOR]

In this study we present a steady-state adaptation of the thermodynamically motivated stress fiber (SF) model of Vigliotti et al. (2015) . We implement this steady-state formulation in a non-local finite element setting where we also consider global conservation of the total number of cytoskeletal proteins within the cell, global conservation of the number of binding integrins on the cell membrane, and adhesion limiting ligand density on the substrate surface. We present a number of simulations of cell spreading in which we consider a limited subset of the possible deformed spread-states assumed by the cell in order to examine the hypothesis that free energy minimization drives the process of cell spreading. Simulations suggest that cell spreading can be viewed as a competition between (i) decreasing cytoskeletal free energy due to strain induced assembly of cytoskeletal proteins into contractile SFs, and (ii) increasing elastic free energy due to stretching of the mechanically passive components of the cell. The computed minimum free energy spread area is shown to be lower for a cell on a compliant substrate than on a rigid substrate. Furthermore, a low substrate ligand density is found to limit cell spreading. The predicted dependence of cell spread area on substrate stiffness and ligand density is in agreement with the experiments of Engler et al. (2003) . We also simulate the experiments of Théry et al. (2006) , whereby initially circular cells deform and adhere to “V-shaped” and “Y-shaped” ligand patches. Analysis of a number of different spread states reveals that deformed configurations with the lowest free energy exhibit a SF distribution that corresponds to experimental observations, i.e. a high concentration of highly aligned SFs occurs along free edges, with lower SF concentrations in the interior of the cell. In summary, the results of this study suggest that cell spreading is driven by free energy minimization based on a competition between decreasing cytoskeletal free energy and increasing passive elastic free energy. [ABSTRACT FROM AUTHOR]

Objective To determine whether using the 2010 World Health Organization (WHO) semen parameter reference values to select varicocelectomy candidates may exclude infertile men who can potentially benefit from this treatment. With the application of the 2010 WHO semen parameter thresholds, some men previously considered to have abnormal semen parameters would now be considered normozoospermic. Methods We conducted a retrospective review of infertile men with varicocele and identified those with abnormal semen parameters according to WHO 1992 or 1999 standards but normozoospermic by WHO 2010 standards. We compared outcomes (semen parameters and spontaneous pregnancy) of couples undergoing varicocelectomy with those choosing observation. Results We identified 445 infertile men with varicocele and abnormal semen parameters by WHO 1992 or 1999 standards. Fifty-six of 445 men (13%) were normozoospermic by WHO 2010. Thirty-two of 56 (57%) of these normozoospermic men elected to have varicocelectomy, and 24 of 56 men (43%) choosing observation. In these normozoospermic men (by WHO 2010), varicocelectomy was associated with a significant increase in sperm concentration (50 ± 35 × 10 6 /mL [postsurgery] vs 32 ± 23 × 10 6 /mL [presurgery]; P = .003). Although not statistically significant, the clinical pregnancy rate was higher in the varicocelectomy group compared with the observation group (52% vs 38%; P = .37). Conclusion Varicocelectomy may be beneficial in those men with clinical varicocele and abnormal semen parameters by WHO 1992 or 1999 standards but now normozoospermic by WHO 2010 standards. Applying the 2010 WHO semen parameter reference values into practice may result in missed opportunities to correct treatable causes of male infertility. [ABSTRACT FROM AUTHOR]

Abstract: Anisotropic damage initiation criteria were developed for extended finite element method (XFEM) prediction of crack initiation and propagation in cortical bone. This anisotropic damage model was shown to accurately predict the dependence of crack propagation patterns and fracture toughness on mode mixity and on osteon orientations, as observed experimentally. Four initiation criteria were developed to define crack trajectories relative to osteon orientations and max principal stress for single and mixed mode fracture. Alternate failure strengths for tensile and compressive loading were defined to simulate the asymmetric failure of cortical bone. The dependence of cortical bone elasticity and failure properties on osteon orientation is analogous to the dependence of composite properties on fibre orientation. Hence, three of the criteria developed in the present study were based upon the Hashin damage criteria. The fourth criterion developed was defined in terms of the max principal stress. This criterion initiated off axis crack growth perpendicular to the direction of the max principal stress. The unique set of parameters calibrated accurately predicted; (i) the relationship between fracture energy and osteon alignment, (ii) the alternate crack patterns for both varying osteon orientations and loading angle. Application of the developed anisotropic damage models to cortical bone screw pullout highlights the potential application for orthopaedic device design evaluation. [Copyright &y& Elsevier]

As a first line option in the treatment of acute ischemic stroke (AIS), direct aspiration is a fast and effective technique with promising outcomes. In silico models are widely used for design and preclinical assessment of new developed devices and therapeutic methods. Accurate modelling of the mechanical behaviour of blood clot is a key factor in the design and simulation of aspiration devices. In this study we develop a new constitutive model which incorporates the unrecoverable plastic deformation of clots. The model is developed based on the deformation-induced microstructural changes in fibrin network, including the formation and dissociation of the cross-links between fibrin fibres. The model is calibrated using previously reported experimentally measured permanent clot deformation following uniaxial stretching. The calibrated plasticity model is then used to simulate aspiration thrombectomy. Results reveal that inclusion of permanent plastic deformation results in ∼ 15 % increase in clot aspiration length at an applied aspiration pressure of 100 mmHg. The constitutive law developed in this study provides a basis for improved design and evaluation of novel aspiration catheters leading to increased first-pass revascularization rate. [ABSTRACT FROM AUTHOR]

Cardiac hypertrophy is an adaption of the heart to a change in cardiovascular loading conditions. The current understanding is that progression may be stress or strain driven, but the multi-scale nature of the cellular remodelling processes have yet to be uncovered. In this study, we develop a model of the contractile left ventricle, with the active cell tension described by a thermodynamically motivated cross-bridge cycling model. Simulation of the transient recruitment of myosin results in correct patterns of ventricular pressure predicted over a cardiac cycle. We investigate how changes in tissue loading and associated deviations in transient force generation can drive restructuring of cellular myofibrils in the heart wall. Our thermodynamic framework predicts in-series sarcomere addition (eccentric remodelling) in response to volume overload, and sarcomere addition in parallel (concentric remodelling) in response to valve and signalling disfunction. This framework provides a significant advance in the current understanding of the fundamental sub-sarcomere level biomechanisms underlying cardiac remodelling. Simulations reveal that pathological tissue loading conditions can significantly alter actin-myosin cross-bridge cycling over the course of the cardiac cycle. The resultant variation in sarcomere stress pushes an imbalance between the internal free energy of the myofibril and that of unbound contractile proteins, initiating remodelling. The link between cross-bridge thermodynamics and myofibril remodelling proposed in this study may significantly advance current understanding of cardiac disease onset. Image 1 [ABSTRACT FROM AUTHOR]

• Laminated fracture fixation plates can support physiological levels of loading. • The ply layup significantly influences the bending stiffness of the implants. • Micro-mechanical analysis uncovers the precise fibre-matrix interface strength. Carbon fibre reinforced PEEK (CF/PEEK) laminates provide mechanical advantages over homogenous metal osteo-synthesis implants, e.g. radiolucency, fatigue strength and strength to weight ratio. Implants can be designed with custom anisotropic material properties, thus enabling the engineer to tailor the overall stiffness of the implant to the specific loading conditions it will experience in vivo. In the current study a multi-scale computational investigation of idealised distal radius fracture fixation plate (DRP) is conducted. Physiological loading conditions are applied to macro-scale finite element models of DRPs. The mechanical response is compared for several CF/PEEK laminate layups to examine the effect of ply layup design. The importance of ply orientation in laminated DRPs is highlighted. A high number of 0° plies near the outer surfaces results in a greater bending strength while the addition of 45° plies increases the torsional strength of the laminates. Intra-laminar transverse tensile failure is predicted as the primary mode of failure. A micro-mechanical analysis of the CF/PEEK microstructure uncovers the precise mechanism under-lying intra-laminar transverse tensile crack to be debonding of the PEEK matrix from carbon fibres. Plastic strains in the matrix material are not sufficiently high to result in ductile failure of the matrix. The findings of this study demonstrate the significant challenge in the design and optimisation of fibre reinforced laminated composites for orthopaedic applications, highlighting the importance of multi-scale modelling for identification of failure mechanisms. [ABSTRACT FROM AUTHOR]

Abstract Blade element momentum (BEM) modelling offers a computationally inexpensive means of analysing turbine performance. Lift and drag coefficient data-sets specific to the operating conditions of the turbine must be input into a BEM model. However, such data is not typically available over the wide range of Reynolds number (Re) and angle of attack (α) encountered by vertical axis turbines. This paper presents a computational fluid dynamics (CFD) approach, based on transitional flow turbulence modelling, to determine lift and drag coefficients for a symmetric hydrofoil. Results are validated against published experimental data for a wide range of α and Re. It is demonstrated that BEM models provide improved predictions of vertical axis turbine performance when CFD generated lift and drag coefficients are used as input, rather than coefficients generated by the widely used panel-method. The combined CFD-based BEM methodology achieves a similar level of accuracy to a full CFD turbine model while providing a significant reduction in computational cost. The modelling approach and hydrofoil data-set developed in this study can be directly utilised for the design and optimisation of next-generation non-straight bladed vertical axis turbine designs which operate over a wide range of α and Re. Highlights • CFD methodology developed for hydrodynamic analysis of a hydrofoil. • Lift and drag established for a range of angles of attack and Reynolds numbers. • Accuracy of BEM model is improved when CFD derived data-sets are used as model input. • Full CFD study of vertical-axis turbine carried out. • Accuracy of CFD-based BEM is comparable to full CFD study at much less computational cost. [ABSTRACT FROM AUTHOR]

Development of in-silico models of patient-specific cerebral artery networks presents several significant technical challenges: (i) The resolution and smoothness of medical CT images are much lower than the required element/cell length for FEA/CFD/FSI models; (ii) contact between vessels, and indeed self contact of high tortuosity vessel segments are not clearly identifiable from medical CT images. Commercial model construction software does not provide customised solutions for such technical challenges, with the result that accurate, efficient and automated development of patient-specific models of the cerebral vessels is not facilitated. This paper presents the development of a customised and highly automated platform for the generation of high resolution patient-specific FEA/CFD/FSI models from clinical images. This platform is used to perform the first fluid–structure-interaction patient-specific analysis of blood flow and artery deformation of an occluded cerebral vessel. Results demonstrate that in addition to flow disruption, clot occlusion significantly alters the geometry and strain distribution in the vessel network, with the blocked M2 segment undergoing axial elongation. The new computational approach presented in this study can be further developed as a clinical diagnostic tool and as a platform for thrombectomy device design. [ABSTRACT FROM AUTHOR]

Abstract: A computational investigation of proximal humeral fracture fixation has been conducted. Four devices were selected for the study; a locking plate, intramedullary nail (IM Nail), K-wires and a Bilboquet device. A 3D model of a humerus was created using a process of thresholding based on the grayscale values of a CT scan of an intact humerus. An idealised three part fracture was created in addition to removing a standard volume from the humeral head as a representation of bone voids that occur as a result of the injury. All finite element simulations conducted represent 90° arm abduction. Simulations were conducted to investigate the effect of filling this bone void with calcium phosphate cement for each device. The effect of constructing devices from carbon fibre polyetheretherketone (CFPEEK) was investigated. Simulations of cement reinforced devices predict greater stability for each device. The average unreinforced fracture line opening (FLO) is reduced by 48.5% for metallic devices with a lesser effect on composite devices with FLO reduced by 23.6%. Relative sliding (shear displacement) is also reduced between fracture fragments by an average of 58.34%. CFPEEK device simulations predict reduced stresses at the device–bone interface. [Copyright &y& Elsevier]

Changes in acute ischemic stroke thrombi structure and composition may result in significant differences in treatment responsiveness. Ischemic stroke patients are often treated with a thrombolytic agent to dissolve thrombi, however these patients may subsequently undergo mechanical thrombectomy to remove the occlusive clot. We set out to determine if rt-PA thrombolysis treatment of blood clots changes their mechanical properties, which in turn may impact mechanical thrombectomy. Using a design-of-experiment approach, ovine clot analogues were prepared with varying composition and further exposed to different levels of compaction force to simulate the effect of arterial blood pressure. Finally, clots were treated with three r-tPA doses for different durations. Clot mass and mechanical behaviour was analysed to assess changes due to (i) Platelet driven contraction (ii) Compaction force and (iii) Thrombolysis. Clots that were exposed to r-tPA for longer duration showed significant reduction in clot mass (p < 0.001). Exposure time to r-tPA (p < 0.001) was shown to be an independent predictor of lower clot stiffness. A decrease in energy dissipation ratio during mechanical compression was associated with longer exposure time in r-tPA (p = 0.001) and a higher platelet concentration ratio (p = 0.018). The dose of r-tPA was not a significant factor in reducing clot mass or changing mechanical properties of the clots. Fibrinolysis reduces clot stiffness which may explain increased distal clot migration observed in patients treated with r-tPA and should be considered as a potential clot modification factor before mechanical thrombectomy. [ABSTRACT FROM AUTHOR]

Treatment of acute ischemic stroke has been recently improved with the introduction of endovascular mechanical thrombectomy, a minimally invasive procedure able to remove a clot using aspiration devices and/or stent-retrievers. Despite the promising and encouraging results, improvements to the procedure and to the stent design are the focus of the recent efforts. Computational studies can pave the road to these improvements, providing their ability to describe and accurately reproduce a real procedure. A patient with ischemic stroke due to intracranial large vessel occlusion was selected and after the creation of the cerebral vasculature from computed tomography images and a histologic analysis to determine the clot composition, the entire thrombectomy procedure was virtually replicated. As in the real situation, the computational replica showed that two attempts were necessary to remove the clot, as a result of the position of the stent retriever with respect to the clot. Furthermore, the results indicated that clot fragmentation did not occur as the deformations were mainly in a compressive state without the possibility for clot cracks to propagate. The accurate representation of the procedure can be used as an important step for operative optimization planning and future improvements of stent designs. [ABSTRACT FROM AUTHOR]