A mechanical approach to understanding the impact of the nematode Anguillicoloides crassus on the European eel swimbladder.

One of the most detrimental factors in the drastic decline of the critically endangered European eel (Anguilla anguilla) was the inadvertent introduction of the invasive nematode Anguillicoloides crassus Infection primarily affects the swimbladder, a gas-filled organ that enables the eel to control its depth in the water. A reduction in swimbladder function may be fatal for eel undergoing their spawning migration to the Sargasso Sea, a journey of over 5000 km. Although the physiological damage caused by this invasive parasite is well studied through the use of quantifiable gross pathological indices, providing a good measure of the swimbladder health status, they cannot separate the role of mechanical and morphological damage. Our study examined the appropriateness of three commonly used indices as a measure of mechanical damage by performing uniaxial tensile tests on swimbladder specimens obtained from an infected eel population. When the test results were compared with the gross pathological indices it was found that thickness correlated most strongly with mechanical damage, both confirming and, more importantly, explaining the counterintuitive findings of earlier work. In a damaged swimbladder, the immune response leads to a trade-off; increasing wall thickness raises the pressure required for organ rupture but decreases strength. The results indicate that for moderate infection the mechanical integrity of the swimbladder can be maintained. For severe infection, however, a reduction in mechanical integrity may reach a tipping point, thereby affecting the successful completion of their oceanic migration.

Sensitivity-based virtual fields for the non-linear virtual fields method.

The virtual fields method is an approach to inversely identify material parameters using full-field deformation data. In this manuscript, a new set of automatically-defined virtual fields for non-linear constitutive models has been proposed. These new sensitivity-based virtual fields reduce the influence of noise on the parameter identification. The sensitivity-based virtual fields were applied to a numerical example involving small strain plasticity; however, the general formulation derived for these virtual fields is applicable to any non-linear constitutive model. To quantify the improvement offered by these new virtual fields, they were compared with stiffness-based and manually defined virtual fields. The proposed sensitivity-based virtual fields were consistently able to identify plastic model parameters and outperform the stiffness-based and manually defined virtual fields when the data was corrupted by noise.

Local mechanical properties of human ascending thoracic aneurysms.

Ascending thoracic aortic aneurysms (ATAAs) are focal, asymmetric dilatations of the aortic wall which are prone to rupture. To identify potential rupture locations in advance, it is necessary to consider the inhomogeneity of the ATAA at the millimeter scale. Towards this end, we have developed a combined experimental and computational approach using bulge inflation tests, digital image correlation (DIC), and an inverse membrane approach to characterize the pointwise stress, strain, and hyperelastic properties of the ATAA. Using this approach, the pointwise hyperelastic material properties were identified on 10 human ATAA samples collected from patients undergoing elective surgery to replace their ATAAs with a graft. Our method was able to capture the varying levels of heterogeneity in the ATAA from regional to local. It was shown for the first time that the material properties in the ATAA are unmistakably heterogeneous at length scales between 1mm and 1cm, which are length scales where vascular tissue is typically treated as homogeneous. The distributions of the material properties for each patient were also examined to study the inter- and intra-patient variability. Large inter-subject variability was observed in the elastic properties.

Patient specific stress and rupture analysis of ascending thoracic aneurysms.

An ascending thoracic aortic aneurysm (ATAA) is a serious medical condition which, more often than not, requires surgery. Aneurysm diameter is the primary clinical criterion for determining when surgical intervention is necessary but, biomechanical studies have suggested that the diameter criterion is insufficient. This manuscript presents a method for obtaining the patient specific wall stress distribution of the ATAA and the retrospective rupture risk for each patient. Five human ATAAs and the preoperative dynamic CT scans were obtained during elective surgeries to replace each patient's aneurysm with a synthetic graft. The material properties and rupture stress for each tissue sample were identified using bulge inflation tests. The dynamic CT scans were used to generate patient specific geometries for a finite element (FE) model of each patient's aneurysm. The material properties from the bulge inflation tests were implemented in the FE model and the wall stress distribution at four different pressures was estimated. Three different rupture risk assessments were compared: the maximum diameter, the rupture risk index, and the overpressure index. The peak wall stress values for the patients ranged from 28% to 94% of the ATAA's failure stress. The rupture risk and overpressure indices were both only weakly correlated with diameter (ρ=-0.29, both cases). In the future, we plan to conduct a large experimental and computational study that includes asymptomatic patients under surveillance, patients undergoing elective surgery, and patients who have experienced rupture or dissection to determine if the rupture risk index or maximum diameter can meaningfully differentiate between the groups.

Pointwise characterization of the elastic properties of planar soft tissues: application to ascending thoracic aneurysms.

In this manuscript, we present a combined experimental and computational technique that can identify the heterogeneous elastic properties of planar soft tissues. By combining inverse membrane analysis, digital image correlation, and bulge inflation tests, we are able to identify a tissue's mechanical properties locally. To show how the proposed method could be implemented, we quantified the heterogeneous material properties of a human ascending thoracic aortic aneurysm (ATAA). The ATAA was inflated at a constant rate using a bulge inflation device until it ruptured. Every 3 kPa images were taken using a stereo digital image correlation system. From the images, the three-dimensional displacement of the sample surface was determined. A deforming NURBS mesh was derived from the displacement data, and the local strains were computed. The wall stresses at each pressure increment were determined using inverse membrane analysis. The local material properties of the ATAA were then identified using the pointwise stress and strain data. To show that it is necessary to consider the heterogeneous distribution of the mechanical properties in the ATAA, three different forward finite element simulations using pointwise, elementwise, and homogeneous material properties were compared. The forward finite element predictions revealed that heterogeneous nature of the ATAA must be accounted for to accurately reproduce the stress-strain response.

Histo-mechanical properties of the swine cardinal and uterosacral ligaments.

The focus of this study was to determine the structural and mechanical properties of two major ligaments that support the uterus, cervix, and vagina: the cardinal ligament (CL) and the uterosacral ligament (USL). The adult swine was selected as animal model. Histological analysis was performed on longitudinal and cross sections of CL and USL specimens using Masson׳s trichrome and Verhoeff-van Giesson staining methods. Scanning electron microscopy was employed to visualize the through-thickness organization of the collagen fibers. Quasi-static uniaxial tests were conducted on specimens that were harvested from the CL/USL complex of a single swine. Dense connective tissue with a high content of elastin and collagen fibers was observed in the USL. Loose connective tissue with a considerable amount of smooth muscle cells and ground substance was detected in both the CL and USL. Collagen fibers, smooth muscle cells, blood vessels, and nerve fibers were arranged primarily in the plane of the ligaments. The USL was significantly stronger than the CL with higher ultimate stress and tangent modulus of the linear region of the stress-strain curve. Knowledge about the mechanical properties of the CL and USL will aid in the design of novel mesh materials, stretching routines, and surgical procedures for pelvic floor disorders.

A three-dimensional constitutive model for the stress relaxation of articular ligaments.

A new nonlinear constitutive model for the three-dimensional stress relaxation of articular ligaments is proposed. The model accounts for finite strains, anisotropy, and strain-dependent stress relaxation behavior exhibited by these ligaments. The model parameters are identified using published uniaxial stress-stretch and stress relaxation data on human medial collateral ligaments (MCLs) subjected to tensile tests in the fiber and transverse to the fiber directions (Quapp and Weiss in J Biomech Eng Trans ASME 120:757-763, 1998; Bonifasi-Lista et al. in J Orthop Res 23(1):67-76, 2005). The constitutive equation is then used to predict the nonlinear elastic and stress relaxation response of ligaments subjected to shear deformations in the fiber direction and transverse to the fiber direction, and an equibiaxial extension. A direct comparison with stress relaxation data collected by subjecting human MCLs to shear deformation in the fiber direction is presented in order to demonstrate the predictive capabilities of the model.

A nonlinear constitutive model for stress relaxation in ligaments and tendons.

A novel constitutive model that describes stress relaxation in transversely isotropic soft collagenous tissues such as ligaments and tendons is presented. The model is formulated within the nonlinear integral representation framework proposed by Pipkin and Rogers (J. Mech. Phys. Solids. 16:59-72, 1968). It represents a departure from existing models in biomechanics since it describes not only the strain dependent stress relaxation behavior of collagenous tissues but also their finite strains and transverse isotropy. Axial stress-stretch data and stress relaxation data at different axial stretches are collected on rat tail tendon fascicles in order to compute the model parameters. Toward this end, the rat tail tendon fascicles are assumed to be incompressible and undergo an isochoric axisymmetric deformation. A comparison with the experimental data proves that, unlike the quasi-linear viscoelastic model (Fung, Biomechanics: Mechanics of Living Tissues. Springer, New York, 1993) the constitutive law can capture the observed nonlinearities in the stress relaxation response of rat tail tendon fascicles.

Effect of anti-IgE therapy in patients with peanut allergy.

BACKGROUND: Peanut-induced anaphylaxis is an IgE-mediated condition that is estimated to affect 1.5 million people and cause 50 to 100 deaths per year in the United States. TNX-901 is a humanized IgG1 monoclonal antibody against IgE that recognizes and masks an epitope in the CH3 region of IgE responsible for binding to the high-affinity Fc(epsilon) receptor on mast cells and basophils. METHODS: We conducted a double-blind, randomized, dose-ranging trial in 84 patients with a history of immediate hypersensitivity to peanut. Hypersensitivity was confirmed and the threshold dose of encapsulated peanut flour established by a double-blind, placebo-controlled oral food challenge at screening. Patients were randomly assigned in a 3:1 ratio to receive either TNX-901 (150, 300, or 450 mg) or placebo subcutaneously every four weeks for four doses. The patients underwent a final oral food challenge within two to four weeks after the fourth dose. RESULTS: From a mean base-line threshold of sensitivity of 178 to 436 mg of peanut flour in the various groups, the mean increases in the oral-food-challenge threshold were 710 mg in the placebo group, 913 mg in the group given 150 mg of TNX-901, 1650 mg in the group given 300 mg of TNX-901, and 2627 mg in the group given 450 mg of TNX-901 (P<0.001 for the comparison of the 450-mg dose with placebo, and P for trend with increasing dose <0.001). TNX-901 was well tolerated. CONCLUSIONS: A 450-mg dose of TNX-901 significantly and substantially increased the threshold of sensitivity to peanut on oral food challenge from a level equal to approximately half a peanut (178 mg) to one equal to almost nine peanuts (2805 mg), an effect that should translate into protection against most unintended ingestions of peanuts.