Plasma Levels of Polychlorinated Biphenyls, Non-Hodgkin Lymphoma, and Causation

Polychlorinated biphenyls (PCBs) are synthetic chlorinated hydrocarbons that have extensively polluted the environment and bioaccumulated in the food chain. PCBs have been deemed to be probable carcinogens by the Environmental Protection Agency, and exposure to high levels of PCBs has been consistently linked to increased risk of non-Hodgkin lymphoma (NHL). In the present article we present a forensic epidemiologic evaluation of the causal relationship between NHL and elevated PCB levels via application of the Bradford-Hill criteria. Included in the evaluation is a meta-analysis of the results of previously published case-control studies in order to assess the strength of association between NHL and PCBs, resulting in an odds ratio in which the lowest percentile PCB concentration (quartile, quintile, or tertile) has been compared with the highest percentile concentration in the study groups. The weight-adjusted odds ratio for all PCB congeners was 1.43 with a 95% confidence interval of 1.31 to 1.55, indicating a statistically significant causal association with NHL. Because of the lack of an unexposed comparison group, a rationale for the use of a less than 2.0 relative risk causal contribution threshold is presented herein, including an ecologic analysis of NHL incidence and PCB accumulation (as measured by sales volume) over time. The overall results presented here indicate a strong general causal association between NHL and PCB exposure

Biokinetic Mechanisms Linked With Musculoskeletal Health Disparities: Stochastic Models Applying Tikhonov\u27s Theorem to Biomolecule Homeostasis.

Multiscale technology and advanced mathematical models have been developed to control and characterize physicochemical interactions, respectively, enhancing cellular and molecular engineering progress. Ongoing tissue engineering development studies have provided experimental input for biokinetic models examining the influence of static or dynamic mechanical stimuli (Saha, A. K., and Kohles, S. S., 2010, “A Distinct Catabolic to Anabolic Threshold Due to Single-Cell Nanomechanical Stimulation in a Cartilage Biokinetics Model,” J. Nanotechnol. Eng. Med., 1(3) p. 031005; 2010, “Periodic Nanomechanical Stimulation in a Biokinetics Model Identifying Anabolic and Catabolic Pathways Associated With Cartilage Matrix Homeostasis,” J. Nanotechnol. Eng. Med., 1(4), p. 041001). In the current study, molecular regulatory thresholds associated with specific disease disparities are further examined through applications of stochastic mechanical stimuli. The results indicate that chondrocyte bioregulation initiates the catabolic pathway as a secondary response to control anabolic processes. In addition, high magnitude loading produced as a result of stochastic input creates a destabilized balance in homeostasis. This latter modeled result may be reflective of an injurious state or disease progression. These mathematical constructs provide a framework for single-cell mechanotransduction and may characterize transitions between healthy and disease states

An Inverse Method for Predicting Tissue-Level Mechanics from Cellular Mechanical Input

Extracellular matrix (ECM) provides a dynamic three-dimensional structure which translates mechanical stimuli to cells. This local mechanical stimulation may direct biological function including tissue development. Theories describing the role of mechanical regulators hypothesize the cellular response to variations in the external mechanical forces on the ECM. The exact ECM mechanical stimulation required to generate a specific pattern of localized cellular displacement is still unknown. The cell to tissue inverse problem offers an alternative approach to clarify this relationship. Developed for structural dynamics, the inverse dynamics problem translates measurements of local state variables (at the cell level) into an unknown or desired forcing function (at the tissue or ECM level). This paper describes the use of eigenvalues (resonant frequencies), eigenvectors (mode shapes), and dynamic programming to reduce the mathematical order of a simplified cell–tissue system and estimate the ECM mechanical stimulation required for a specified cellular mechanical environment. Finite element and inverse numerical analyses were performed on a simple two-dimensional model to ascertain the effects of weighting parameters and a reduction of analytical modes leading toward a solution. Simulation results indicate that the reduced number of mechanical modes (from 30 to 14 to 7) can adequately reproduce an unknown force time history on an ECM boundary. A representative comparison between cell to tissue (inverse) and tissue to cell (boundary value) modeling illustrates the multiscale applicability of the inverse model

Validation of a Biomechanical Injury and Disease Assessment Platform Applying an Inertial-Based Biosensor and Axis Vector Computation

Inertial kinetics and kinematics have substantial influences on human biomechanical function. A new algorithm for Inertial Measurement Unit (IMU)-based motion tracking is presented in this work. The primary aims of this paper are to combine recent developments in improved biosensor technology with mainstream motion-tracking hardware to measure the overall performance of human movement based on joint axis-angle representations of limb rotation. This work describes an alternative approach to representing three-dimensional rotations using a normalized vector around which an identified joint angle defines the overall rotation, rather than a traditional Euler angle approach. Furthermore, IMUs allow for the direct measurement of joint angular velocities, offering the opportunity to increase the accuracy of instantaneous axis of rotation estimations. Although the axis-angle representation requires vector quotient algebra (quaternions) to define rotation, this approach may be preferred for many graphics, vision, and virtual reality software applications. The analytical method was validated with laboratory data gathered from an infant dummy leg’s flexion and extension knee movements and applied to a living subject’s upper limb movement. The results showed that the novel approach could reasonably handle a simple case and provide a detailed analysis of axis-angle migration. The described algorithm could play a notable role in the biomechanical analysis of human joints and offers a harbinger of IMU-based biosensors that may detect pathological patterns of joint disease and injury

Biomechanical Analysis of Concealed Pack Load Influences on Terrorist Gait Signatures Derived from Gröbner Basis Theory

This project examines kinematic gait parameters as forensic predictors of the influence associated with individuals carrying concealed weighted packs up to 20% of their body weight. An initial inverse dynamics approach combined with computational algebra provided lower limb joint angles during the stance phase of gait as measured from 12 human subjects during normal walking. The following paper describes the additional biomechanical analysis of the joint angle data to produce kinetic and kinematic parameters further characterizing human motion. Results include the rotational velocities and accelerations of the hip, knee, and ankle as well as inertial moments and kinetic energies produced at these joints. The reported findings indicate a non-statistically significant influence of concealed pack load, body mass index, and gender on joint kinetics (p\u3e0.05). Ratios of loaded to unloaded kinematics, however, identified some statistical influence on gait (

Novel Computational Approaches Characterizing Knee Physiotherapy

A knee joint’s longevity depends on the proper integration of structural components in an axial alignment. If just one of the components is abnormally off-axis, the biomechanical system fails, resulting in arthritis. The complexity of various failures in the knee joint has led orthopedic surgeons to select total knee replacement as a primary treatment. In many cases, this means sacrificing much of an otherwise normal joint. Here, we review novel computational approaches to describe knee physiotherapy by introducing a new dimension of foot loading to the knee axis alignment producing an improved functional status of the patient. New physiotherapeutic applications are then possible by aligning foot loading with the functional axis of the knee joint during the treatment of patients with osteoarthritis

An Informational Algorithm as the Basis for Perception-Action Control of the Instantaneous Axes of the Knee

Traditional locomotion studies emphasize an optimization of the desired movement trajectories while ignoring sensory feedback. We propose an information based theory that locomotion is neither triggered nor commanded but controlled. The basis for this control is the information derived from perceiving oneself in the world. Control therefore lies in the human-environment system. In order to test this hypothesis, we derived a mathematical foundation characterizing the energy that is required to perform a rotational twist, with small amplitude, of the instantaneous axes of the knee (IAK). We have found that the joint’s perception of the ground reaction force may be replaced by the co-perception of muscle activation with appropriate intensities. This approach generated an accurate comparison with known joint forces and appears appropriate in so far as predicting the effect on the knee when it is free to twist about the IAK

Ultrasonic Wave Propagation Assessment of Native Cartilage Explants and Hydrogel Scaffolds for Tissue Engineering

Non-destructive techniques characterising the mechanical properties of cells, tissues, and biomaterials provide baseline metrics for tissue engineering design. Ultrasonic wave propagation and attenuation has previously demonstrated the dynamics of extracellular matrix synthesis in chondrocyte-seeded hydrogel constructs. In this paper, we describe an ultrasonic method to analyse two of the construct elements used to engineer articular cartilage in real-time, native cartilage explants and an agarose biomaterial. Results indicated a similarity in wave propagation velocity ranges for both longitudinal (1500-1745 m/s) and transverse (350-950 m/s) waveforms. Future work will apply an acoustoelastic analysis to distinguish between the fluid and solid properties including the cell and matrix biokinetics as a validation of previous mathematical models

Optical Acquisition and Polar Decomposition of the Full-Field Deformation Gradient Tensor Within a Fracture Callus

Tracking tissue deformation is often hampered by material inhomogeneity, so local measurements tend to be insufficient thus lending to the necessity of full-field optical measurements. This study presents a novel approach to factoring heterogeneous deformation of soft and hard tissues in a fracture callus by introducing an anisotropic metric derived from the deformation gradient tensor (F). The deformation gradient tensor contains all the information available in a Green-Lagrange strain tensor, plus the rigid-body rotational components. A recent study [Bottlang et al., J. Biomech. 41(3), 2008] produced full-field strains within ovine fracture calluses acquired through the application of electronic speckle pattern interferometery (ESPI). The technique is based on infinitesimal strain approximation (Engineering Strain) whose scheme is not independent of rigid body rotation. In this work, for rotation extraction, the stretch and rotation tensors were separately determined from F by the polar decomposition theorem. Interfragmentary motions in a fracture gap were characterized by the two distinct mechanical factors (stretch and rotation) at each material point through full-field mapping. In the composite nature of bone and soft tissue, collagen arrangements are hypothesized such that fibers locally aligned with principal directions will stretch and fibers not aligned with the principal direction will rotate and stretch. This approach has revealed the deformation gradient tensor as an appropriate quantification of strain within callus bony and fibrous tissue via optical measurements