Streaming potential is considered one of the most important mechanisms to moderate the function of osteoblasts and osteocytes in bone growth, remodeling and fracture repair. The present study was designed to demonstrate the fluid flow pattern in the cortical bone matrix in an animal model using undecalcified histological techniques. Immediately after injection of ferritin into the tibia nutrient artery of four adult goats, the animals were euthanized. Undecalcified transverse and longitudinal blocks of cortical bone obtained from the tibial diaphysis were immersed in Perl's reagent and embedded in methyl methacrylate. Sections were cut and ground to 30-50 µm thickness for histomorphological evaluation at different magnifications and focusing levels. A serial grinding technique was used to validate the observations made at different focusing levels. As expected, ferritin was observed in the interstitial compartment in both transverse and longitudinal sections. In osteons sectioned transversely, the pattern of centrifugal movement of ferritin marker was demonstrated as single or multiple halos around the Haversian canal. The most apparent halo in osteons with multiple halos was the one found closest to the Haversian canal. The total number of identifiable single or multiple halos increased or was altered when counting was made with higher magnification or at different focusing levels, respectively. Irregular and incomplete ferritin halos indicated structural complexity of the osteons. Overall, the pattern of ferritin movement was consistent with bulk interstitial fluid flow influenced by both hydrostatic pressure and transudation. This study demonstrated for the first time multiple concentric halos of the fluid flow marker ferritin around Haversian canals in the cortical interstitial compartment. The results suggest that the undecalcified technique might be a useful method for qualitative and quantitative studies on cortical fluid flow. Anat Rec 255: 380-387, 1999. 1999 Key words: fluid flow; cortical bone; ferritin transudation; undecalcification; histology; microscopy Mature cortical bone is structurally organized into osteons. Each osteon is roughly cylindrical in shape with concentric lamellae around the vasculature-containing Haversian canal. Between the lamellae lie the ellipsoidal lacunae where the osteocytes reside. Cortical bone has a hierarchical network of flow channels, i.e. the longitudinal Haversian and the transverse Volkmann's canals to the tiny lacunae-canaliculi channels around the bone cells, and the microporosity of the collagen-hydroxyapatite bone matrix (Cooper et al

ObjectivesCerebral microbleeds are associated with the risks of ischemic stroke and intracranial hemorrhage, causing clinical dilemmas for antithrombotic treatment decisions. We aimed to evaluate the risks of intracranial hemorrhage and ischemic stroke associated with microbleeds in patients with atrial fibrillation treated with Vitamin K antagonists, direct oral anticoagulants, antiplatelets, and combination therapy (i.e. concurrent oral anticoagulant and antiplatelet) MethodsWe included patients with documented atrial fibrillation from the pooled individual patient data analysis by the Microbleeds International Collaborative Network. Risks of subsequent intracranial hemorrhage and ischemic stroke were compared between patients with and without microbleeds, stratified by antithrombotic use. ResultsA total of 7,839 patients were included. The presence of microbleeds was associated with an increased relative risk of intracranial hemorrhage (aHR 2.74, 95% confidence interval 1.76 -4.26) and ischemic stroke (aHR 1.29, 95% confidence interval 1.04 -1.59). For the entire cohort, the absolute incidence of ischemic stroke was higher than intracranial hemorrhage regardless of microbleeds burden. However, for the subgroup of patients taking combination of anticoagulant and antiplatelet therapy, the absolute risk of intracranial hemorrhage exceeded that of ischemic stroke in those with 2-4 microbleeds (25 vs 12 per 1,000 patient-years) and ≥11 microbleeds (94 vs 48 per 1,000 patient-years). InterpretationPatients with atrial fibrillation and high burden of microbleeds receiving combination therapy have a tendency of higher rate of intracranial hemorrhage than ischemic stroke, with potential for net harm.Further studies are needed to help optimize stroke preventive strategies in this high-risk group.

We present an implementation of the trimmed serendipity finite element family, using the open-source finite element package Firedrake. The new elements can be used seamlessly within the software suite for problems requiring H 1 , H (curl), or H (div)-conforming elements on meshes of squares or cubes. To test how well trimmed serendipity elements perform in comparison to traditional tensor product elements, we perform a sequence of numerical experiments including the primal Poisson, mixed Poisson, and Maxwell cavity eigenvalue problems. Overall, we find that the trimmed serendipity elements converge, as expected, at the same rate as the respective tensor product elements, while being able to offer significant savings in the time or memory required to solve certain problems.

We present an implementation of the trimmed serendipity finite element family, using the open source finite element package Firedrake. The new elements can be used seamlessly within the software suite for problems requiring 𝐻 1 , 𝐻 (curl), or 𝐻 (div)-conforming elements on meshes of squares or cubes. To test how well trimmed serendipity elements perform in comparison to traditional tensor product elements, we perform a sequence of numerical experiments including the primal Poisson, mixed Poisson, and Maxwell cavity eigenvalue problems. Overall, we find that the trimmed serendipity elements converge, as expected, at the same rate as the respective tensor product elements while being able to offer significant savings in the time or memory required to solve certain problems.