Structural Optimisation: Biomechanics of the Femur

A preliminary iterative 3D meso-scale structural model of the femur was developed, in which bar and shell elements were used to represent trabecular and cortical bone respectively. The cross-sectional areas of the bar elements and the thickness values of the shell elements were adjusted over successive iterations of the model based on a target strain stimulus, resulting in an optimised construct. The predicted trabecular architecture, and cortical thickness distribution showed good agreement with clinical observations, based on the application of a single leg stance load case during gait. The benefit of using a meso-scale structural approach in comparison to micro or macro-scale continuum approaches to predictive bone modelling was achievement of the symbiotic goals of computational efficiency and structural description of the femur.Comment: Accepted by Engineering and Computational Mechanics (Proceedings of the ICE

Numerical modelling of the pelvis and acetabular construct following hip arthroplasty

The study presents finite element models of the acetabular construct and the pelvis. Particular attention is given to investigating the behaviour of the acetabular construct following revision hip arthroplasty, carried out using the Slooff-Ling impaction grafting technique. Mechanical tests are carried out on bone graft, and constitutive models are developed to describe its non-linear elasto-plastic behaviour, for inclusion in finite element analyses. Impaction of bone graft was found to have a significant effect in reducing subsequent development of consolidation plastic strains. A novel approach for the inclusion of muscles and ligaments, in finite element analyses, to provide boundary conditions similar to those found in vivo is also presented. 2D analyses of the acetabular construct, following revision hip arthroplasty, carried out using impaction grafting, indicate that for idealised load cases, rotation of the acetabular cup increases, as the depth of the bone graft bed increases. This indicates that it is advantageous to use the largest practical diameter of acetabular cup. Results from 3D analyses of the hemi pelvis, following revision arthroplasty, indicate that different patterns of migration and rotation of the acetabular cup, within the bone graft bed are associated with different physiological activities. For example walking is seen to cause migration of the cup in the superior direction, and rotation of the cup in abduction. Results from 3D analyses of the pelvis indicate that the inclusion of muscles and ligaments, in place of fixed boundary conditions cause significant changes to the stress distribution observed in the cortical bone, but comparatively minor changes to the stresses in the trabecular bone, and bone graft in the acetabular region

Modeling impact of intertidal foreshore evolution on gravel barrier erosion and wave runup with XBeach-X

This paper provides a sensitivity analysis around how characterizing sandy, intertidal foreshore evolution in XBeach-X impacts on wave runup and morphological change of a vulnerable, composite gravel beach. The study is motivated by a need for confidence in storm-impact modeling outputs to inform coastal management policy for composite beaches worldwide. First, the model is run with the sandy settings applied to capture changes in the intertidal foreshore, with the gravel barrier assigned as a non-erodible surface. Model runs were then repeated with the gravel settings applied to obtain wave runup and erosion of the barrier crest, updating the intertidal foreshore from the previous model outputs every 5, 10 and 15 min, and comparing this with a temporally static foreshore. Results show that the scenario with no foreshore evolution led to the highest wave runup and barrier erosion. The applied foreshore evolution setting update is shown to be a large control on the distribution of freeboard values indicative of overwash hazard and barrier erosion by causing an increase (with 5 min foreshore updates applied) or a decrease (with no applied foreshore updating) in the Iribarren number. Therefore, the sandy, intertidal component should not be neglected in gravel barrier modeling applications given the risk of over- or under-predicting the wave runup and barrier erosion

GBM heterogeneity as a function of variable epidermal growth factor receptor variant III activity.

Abnormal activation of the epidermal growth factor receptor (EGFR) due to a deletion of exons 2-7 of EGFR (EGFRvIII) is a common alteration in glioblastoma (GBM). While this alteration can drive gliomagenesis, tumors harboring EGFRvIII are heterogeneous. To investigate the role for EGFRvIII activation in tumor phenotype we used a neural progenitor cell-based murine model of GBM driven by EGFR signaling and generated tumor progenitor cells with high and low EGFRvIII activation, pEGFRHi and pEGFRLo. In vivo, ex vivo, and in vitro studies suggested a direct association between EGFRvIII activity and increased tumor cell proliferation, decreased tumor cell adhesion to the extracellular matrix, and altered progenitor cell phenotype. Time-lapse confocal imaging of tumor cells in brain slice cultures demonstrated blood vessel co-option by tumor cells and highlighted differences in invasive pattern. Inhibition of EGFR signaling in pEGFRHi promoted cell differentiation and increased cell-matrix adhesion. Conversely, increased EGFRvIII activation in pEGFRLo reduced cell-matrix adhesion. Our study using a murine model for GBM driven by a single genetic driver, suggests differences in EGFR activation contribute to tumor heterogeneity and aggressiveness

Neural responses to facial and vocal expressions of fear and disgust

Neuropsychological studies report more impaired responses to facial expressions of fear than disgust in people with amygdala lesions, and vice versa in people with Huntington's disease. Experiments using functional magnetic resonance imaging (fMRI) have confirmed the role of the amygdala in the response to fearful faces and have implicated the anterior insula in the response to facial expressions of disgust. We used fMRI to extend these studies to the perception of fear and disgust from both facial and vocal expressions. Consistent with neuropsychological findings, both types of fearful stimuli activated the amygdala. Facial expressions of disgust activated the anterior insula and the caudate-putamen; vocal expressions of disgust did not significantly activate either of these regions. All four types of stimuli activated the superior temporal gyrus. Our findings therefore (i) support the differential localization of the neural substrates of fear and disgust; (ii) confirm the involvement of the amygdala in the emotion of fear, whether evoked by facial or vocal expressions; (iii) confirm the involvement of the anterior insula and the striatum in reactions to facial expressions of disgust; and (iv) suggest a possible general role for the perception of emotional expressions for the superior temporal gyrus

Kontribusi USAhatani Ternak Kambing dalam Meningkatkan Pendapatan Petani (Studi Kasus di Desa Batungsel, Kecamatan Pupuan, Kabupaten Tabanan)

The aims of this study were to analyze: (1) goat farm contribution to the farmer\u27s income, (2) minimum farm scale for providing benefit, and (3) financial feasibility of the goat farm. This study was conducted in the Batungsel Village, Pupuan District, Tabanan Regency. Interview used questioner to farmers is done to collect data. Income analysis, BEP (Break Event Point), Profit Rate, and R/C ratio, was used in this study. The results of this study showed that: net income of the farmer from goat farm was Rp. 6,375,000. Profit rate 66.93% and R/C ratio of 1.67 showed that the goat farm was feasible financially. Break Event Point can be attain on Rp. 6,284,393 of the revenue or 8 goat of production. Income from goat farm give the largest contribution to total farmer income. This study indicated that the goat farm can be used as a solution to reducing poverty rate in the villages

Spectroscopy of Globular Clusters in M81

We present moderate-resolution spectroscopy of globular clusters (GCs) around the Sa/Sb spiral galaxy M81 (NGC 3031). Sixteen candidate clusters were observed with the Low Resolution Imaging Spectrograph on the Keck I telescope. All are confirmed as bona fide GCs, although one of the clusters appears to have been undergoing a transient event during our observations. In general, the M81 globular cluster system (GCS) is found to be very similar to the Milky Way (MW) and M31 systems, both chemically and kinematically. A kinematic analysis of the velocities of 44 M81 GCS, (the 16 presented here and 28 from previous work) strongly suggests that the red, metal-rich clusters are rotating in the same sense as the gas in the disk of M81. The blue, metal-poor clusters have halo-like kinematics, showing no evidence for rotation. The kinematics of clusters whose projected galactocentric radii lie between 4 and 8 kpc suggest that they are rotating much more than those which lie outside these bounds. We suggest that these rotating, intermediate-distance clusters are analogous to the kinematic sub-population in the metal-rich, disk GCs observed in the MW and we present evidence for the existence of a similar sub-population in the metal-rich clusters of M31. With one exception, all of the M81 clusters in our sample have ages that are consistent with MW and M31 GCs. One cluster may be as young as a few Gyrs. The correlations between absorption-line indices established for MW and M31 GCs also hold in the M81 cluster system, at least at the upper end of the metallicity distribution (which our sample probes). On the whole, the mean metallicity of the M81 GCS is similar to the metallicity of the MW and M31 GCSs. The projected mass of M81 is similar to the masses of the MW and M31. Its mass profile indicates the presence of a dark matter halo.Comment: 35 pages, including 11 figures and 9 tables. Accepted for publication in the Astronomical Journa

Comparison of DC Bead-irinotecan and DC Bead-topotecan drug eluting beads for use in locoregional drug delivery to treat pancreatic cancer

DC Bead is a drug delivery embolisation system that can be loaded with doxorubicin or irinotecan for the treatment of a variety of liver cancers. In this study we demonstrate that the topoisomerase I inhibitor topotecan hydrochloride can be successfully loaded into the DC Bead sulfonate-modified polyvinyl alcohol hydrogel matrix, resulting in a sustained-release drug eluting bead (DEBTOP) useful for therapeutic purposes. The in vitro drug loading capacity, elution characteristics and the effects on mechanical properties of the beads are described with reference to our previous work with irinotecan hydrochloride (DEBIRI). Results showed that drug loading was faster when the solution was agitated compared to static loading and a maximum loading of ca. 40–45 mg topotecan in 1 ml hydrated beads was achievable. Loading the drug into the beads altered the size, compressibility moduli and colour of the bead. Elution was shown to be reliant on the presence of ions to perform the necessary exchange with the electrostatically bound topotecan molecules. Topotecan was shown by MTS assay to have an IC50 for human pancreatic adenocarcinoma cells (PSN-1) of 0.22 and 0.27 lM compared to 28.1 and 19.2 lM for irinotecan at 48 and 72 h, respectively. The cytotoxic efficacy of DEBTOP on PSN-1 was compared to DEBIRI. DEPTOP loaded at 6 & 30 mg ml-1, like its free drug form, was shown to be more potent than DEBIRI of comparable doses at 24, 48 & 72 h using a slightly modified MTS assay. Using a PSN-1 mouse xenograft model, DEBIRI doses of 3.3–6.6 mg were shown to be well tolerated (even with repeat administration) and effective in reducing the tumour size. DEBTOP however, was lethal after 6 days at doses of 0.83–1.2 mg but demonstrated reasonable efficacy and tolerability (again with repeat injection possible) at 0.2–0.4 mg doses. Care must therefore be taken when selecting the dose of topotecan to be loaded into DC Bead given its greater potency and potential toxicity

Combining regional and local scale coastal flood risk assessment and hazard modelling

This paper presents a method to combine regional- and local-scale flood risk assessment with numerical modelling of coastal inundation under sea defence breaching. We review existing coastal defence inspection reports, and by combining structure condition, deterioration, hinterland significance and inundation probability, we generate a risk score for each stretch of coastal defence in North Wales and North-West England. A frontage in North-East Wales deemed to be at high risk was used for a detailed hazard study using a flood model (LISFLOOD-FP), where a 0.5% probability flood was modelled under various sea-level rise and defence breaching scenarios. Flood hazard ratings given partial and total failure of the sea wall under present day, 2050 and 2100, and H++ sea-level scenarios are simulated to identify future flood risk to key infrastructure within the coastal community