Subchondral bone density distribution of the talus in clinically normal Labrador Retrievers

Background: Bones continually adapt their morphology to their load bearing function. At the level of the subchondral bone, the density distribution is highly correlated with the loading distribution of the joint. Therefore, subchondral bone density distribution can be used to study joint biomechanics non-invasively. In addition physiological and pathological joint loading is an important aspect of orthopaedic disease, and research focusing on joint biomechanics will benefit veterinary orthopaedics. This study was conducted to evaluate density distribution in the subchondral bone of the canine talus, as a parameter reflecting the long-term joint loading in the tarsocrural joint. Results: Two main density maxima were found, one proximally on the medial trochlear ridge and one distally on the lateral trochlear ridge. All joints showed very similar density distribution patterns and no significant differences were found in the localisation of the density maxima between left and right limbs and between dogs. Conclusions: Based on the density distribution the lateral trochlear ridge is most likely subjected to highest loads within the tarsocrural joint. The joint loading distribution is very similar between dogs of the same breed. In addition, the joint loading distribution supports previous suggestions of the important role of biomechanics in the development of OC lesions in the tarsus. Important benefits of computed tomographic osteoabsorptiometry (CTOAM), i.e. the possibility of in vivo imaging and temporal evaluation, make this technique a valuable addition to the field of veterinary orthopaedic research

A practical view of fine-mapping and gene prioritization in the post-genome-wide association era

Over the past 15 years, genome-wide association studies (GWASs) have enabled the systematic identification of genetic loci associated with traits and diseases. However, due to resolution issues and methodological limitations, the true causal variants and genes associated with traits remain difficult to identify. In this post-GWAS era, many biological and computational fine-mapping approaches now aim to solve these issues. Here, we review fine-mapping and gene prioritization approaches that, when combined, will improve the understanding of the underlying mechanisms of complex traits and diseases. Fine-mapping of genetic variants has become increasingly sophisticated: initially, variants were simply overlapped with functional elements, but now the impact of variants on regulatory activity and direct variant-gene 3D interactions can be identified. Moreover, gene manipulation by CRISPR/Cas9, the identification of expression quantitative trait loci and the use of co-expression networks have all increased our understanding of the genes and pathways affected by GWAS loci. However, despite this progress, limitations including the lack of cell-type- and disease-specific data and the ever-increasing complexity of polygenic models of traits pose serious challenges. Indeed, the combination of fine-mapping and gene prioritization by statistical, functional and population-based strategies will be necessary to truly understand how GWAS loci contribute to complex traits and diseases

PERFORMANCE DETERMINING FACTORS IN ELITE SPRINTERS DURING SPRINT START AND TWO FOLLOWING SUCCESSIVE SUPPORTS

Sprint start out of the blocks and successive acceleration are technically challenging as the athlete goes from a bended to a forward leaning position. Therefore, the body center of mass (COM) has to be accelerated forward and upwards. Optimal sprinting performance relies on attaining maximal forward acceleration. However, adequate vertical acceleration must be generated to reach sufficient height to prepare for the following step (Weyand, 2000). Horizontal acceleration is mainly determined by the horizontal ground reaction force that will affect sprint velocity and therefore final sprint performance (Mero, 1988). Kinematics and kinetics of the start action and maximal sprinting were intensively studied; however little is known on the transition from the set position to the running position during the first two strides. This study aims to identify the factors in the start action as well as in the first and second contact after block clearance that determine sprinting performance in terms of speed and acceleration

Magnetoresistance of a semiconducting magnetic wire with domain wall

We investigate theoretically the influence of the spin-orbit interaction of Rashba type on the magnetoresistance of a semiconducting ferromagnetic nanostructure with a laterally constrained domain wall. The domain wall is assumed sharp (on the scale of the Fermi wave length of the charge carriers). It is shown that the magnetoresistance in such a case can be considerably large, which is in a qualitative agreement with recent experimental observations. It is also shown that spin-orbit interaction may result in an increase of the magnetoresistance. The role of localization corrections is also briefly discussed.Comment: 5 pages, 2 figure

Modelling Cyclic Walking in Femurs With Metastatic Lesions:Femur-Specific Accumulation of Plasticity

Introduction Clinical fracture risk assessment in metastatic bone disease is extremely difficult, but subject-specific finite element (FE) modelling may improve these assessments in the future [Derikx, 2015]. By coupling to musculoskeletal modelling, realistic loading conditions can be implemented in FE analysis. However, it is unknown whether such analyses require complex elastic-plastic material models, or whether a linear elastic calculation already provides a reasonable prediction of fracture. Moreover, plastic deformation may accumulate over time, which is ignored by linear elastic calculations. In this study we compared linear and non-linear fracture predictions under realistic loading conditions in two patients with metastatic bone disease. Methods Two patients (P1, P2) with lytic lesions were included. Patient-specific femoral geometry and bone density were retrieved from quantitative CT-scans; the latter was used for implementing element-specific material behaviour [Keyak, 2005]. Muscle forces and hip contact forces acting on the femur during walking were calculated using musculoskeletal modelling (one typical case, adapted from [Wesseling, 2014]), and subsequently normalized to the patient’s body weight. Muscle forces were applied to attachment points that were morphed onto the patient femurs. Hip contact forces were applied to a cup mimicking the acetabulum, via a control node in the hip joint centre. Two simulations were run for each patient: a linear elastic analysis simulating a single walk cycle and a non-linear elastic-plastic analysis simulating 10 subsequent walk cycles. The safety factor (SF; yield stress/Von Mises stress) and plasticity were studied as measures of femoral failure in the linear and non-linear simulations, respectively, and compared between patients. Results The volume of elements with SF<1 (Figure 1A) as well as the volume of elements that underwent plastic deformation (Figure 1B) was highest in the femur of P1. In P1 the volume of plastic deformation increased over the loading cycles and eventually exceeded the peak volume of elements with SF<1 in the linear analysis. In P2, the volume of plasticity more or less stabilized after two loading cycles, and eventually resembled the volume of elements with SF<1 in the linear analysis. Discussion These preliminary results suggest that accumulation of plasticity under cyclic loading is femur-specific. Due to the variable and local weakening of the bone strength by metastatic lesions, relatively small changes in magnitude or direction of loading may initiate local failure and catalyze progressive failure in subsequent loading cycles. Hence, in some cases a linear analysis is sufficient, while in others it is not. Non-linear material behaviour and cyclic loading conditions are therefore required to capture these phenomena