In this paper we present a new formulation of the boundary condition at static and moving solid walls in SPH simulations. Our general approach is both applicable to two and three dimensions and is ...very simple compared to previous wall boundary formulations. Based on a local force balance between wall and fluid particles we apply a pressure boundary condition on the solid particles to prevent wall penetration. This method can handle sharp corners and complex geometries as is demonstrated with several examples. A validation shows that we recover hydrostatic equilibrium conditions in a static tank, and a comparison of the classical dam break simulation with state-of-the-art results in literature shows good agreement. We simulate various problems such as the flow around a cylinder and the backward facing step at Re=100 to demonstrate the general applicability of this new method.
The standard weakly-compressible SPH method suffers from particle clumping and void regions for high Reynolds number flows and when negative pressures occur in the flow. As a remedy, a new algorithm ...is proposed that combines the homogenization of the particle configuration by a background pressure while at the same time reduces artificial numerical dissipation. The transport or advection velocity of particles is modified and an effective stress term occurs in the momentum balance that accounts for the difference between advection velocity times particle density and actual particle momentum. The present formulation can be applied for internal flows where the density summation is applicable. A wide range of test cases demonstrates unprecedented accuracy and stability of the proposed modification even at previously infeasible conditions.
In this paper, we propose a new surface-tension formulation for multi-phase smoothed particle hydrodynamics (SPH). To obtain a stable and accurate scheme for surface curvature, a new reproducing ...divergence approximation without the need for a matrix inversion is derived. Furthermore, we introduce a density-weighted color-gradient formulation to reflect the reality of an asymmetrically distributed surface-tension force. We validate our method with analytic solutions and demonstrate convergence for different cases. Furthermore, we show that our formulation can handle phase interfaces with density and viscosity ratios of up to 1000 and 100, respectively. Finally, complex three-dimensional simulations including breakup of an interface demonstrate the capabilities of our method.
Denosumab is a fully human monoclonal antibody to the receptor activator of nuclear factor-kappaB ligand (RANKL) that blocks its binding to RANK, inhibiting the development and activity of ...osteoclasts, decreasing bone resorption, and increasing bone density. Given its unique actions, denosumab may be useful in the treatment of osteoporosis.
We enrolled 7868 women between the ages of 60 and 90 years who had a bone mineral density T score of less than -2.5 but not less than -4.0 at the lumbar spine or total hip. Subjects were randomly assigned to receive either 60 mg of denosumab or placebo subcutaneously every 6 months for 36 months. The primary end point was new vertebral fracture. Secondary end points included nonvertebral and hip fractures.
As compared with placebo, denosumab reduced the risk of new radiographic vertebral fracture, with a cumulative incidence of 2.3% in the denosumab group, versus 7.2% in the placebo group (risk ratio, 0.32; 95% confidence interval CI, 0.26 to 0.41; P<0.001)--a relative decrease of 68%. Denosumab reduced the risk of hip fracture, with a cumulative incidence of 0.7% in the denosumab group, versus 1.2% in the placebo group (hazard ratio, 0.60; 95% CI, 0.37 to 0.97; P=0.04)--a relative decrease of 40%. Denosumab also reduced the risk of nonvertebral fracture, with a cumulative incidence of 6.5% in the denosumab group, versus 8.0% in the placebo group (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01)--a relative decrease of 20%. There was no increase in the risk of cancer, infection, cardiovascular disease, delayed fracture healing, or hypocalcemia, and there were no cases of osteonecrosis of the jaw and no adverse reactions to the injection of denosumab.
Denosumab given subcutaneously twice yearly for 36 months was associated with a reduction in the risk of vertebral, nonvertebral, and hip fractures in women with osteoporosis. (ClinicalTrials.gov number, NCT00089791.)
Osteoporosis poses a significant public health issue. National Societies have developed Guidelines for the diagnosis and treatment of this disorder with an effort of adapting specific tools for risk ...assessment on the peculiar characteristics of a given population. The Italian Society for Osteoporosis, Mineral Metabolism and Bone Diseases (SIOMMMS) has recently revised the previously published Guidelines on the diagnosis, riskassessment, prevention and management of primary and secondary osteoporosis. The guidelines were first drafted by a working group and then approved by the board of SIOMMMS. Subsequently they received also the endorsement of other major Scientific Societies that deal with bone metabolic disease. These recommendations are based on systematic reviews of the best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on leading experts' experience and opinion, and on good clinical practice. The osteoporosis prevention should be based on the elimination of specific risk factors. The use of drugs registered for the treatment of osteoporosis are recommended when the benefits overcome the risk, and this is the case only when the risk of fracture is rather high as measured with variables susceptible to pharmacological effect. DeFRA (FRAX® derived fracture risk assessment) is recognized as a useful tool for easily estimate the long-term fracture risk. Several secondary forms of osteoporosis require a specific diagnostic and therapeutic management.
Background: Strontium ranelate, a new oral drug shown to reduce vertebral fracture risk in postmenopausal women with osteoporosis, was studied in the Treatment of Peripheral Osteoporosis (TROPOS) ...study to assess its efficacy and safety in preventing nonvertebral fractures also.
Methods: Strontium ranelate (2 g/d) or placebo were randomly allocated to 5091 postmenopausal women with osteoporosis in a double-blind placebo-controlled 5-yr study with a main statistical analysis over 3 yr of treatment.
Findings: In the entire sample, relative risk (RR) was reduced by 16% for all nonvertebral fractures (P = 0.04), and by 19% for major fragility fractures (hip, wrist, pelvis and sacrum, ribs and sternum, clavicle, humerus) (P = 0.031) in strontium ranelate-treated patients in comparison with the placebo group. Among women at high risk of hip fracture (age ≥74 yr and femoral neck bone mineral density T score ≤−3, corresponding to −2.4 according to NHANES reference) (n = 1977), the RR reduction for hip fracture was 36% (P = 0.046). RR of vertebral fractures was reduced by 39% (P < 0.001) in the 3640 patients with spinal x-rays and by 45% in the subgroup without prevalent vertebral fracture.
Strontium ranelate increased bone mineral density throughout the study, reaching at 3 yr (P < 0.001): +8.2% (femoral neck) and +9.8% (total hip).
Incidence of adverse events (AEs) was similar in both groups.
Conclusion: This study shows that strontium ranelate significantly reduces the risk of all nonvertebral and in a high-risk subgroup, hip fractures over a 3-yr period, and is well tolerated. It confirms that strontium ranelate reduces vertebral fractures. Strontium ranelate offers a safe and effective means of reducing the risk of fracture associated with osteoporosis.
Postmenopausal osteoporosis is mainly caused by increased bone remodeling resulting from estrogen deficiency. Indications for treatment are based on low areal bone mineral density (aBMD, T-score ≤ ...−2.5), typical fragility fractures (spine or hip), and more recently, an elevated 10-year fracture probability (by FRAX®). In contrast, there is no clear definition of osteoporosis nor intervention thresholds in younger individuals. Low aBMD in a young adult may reflect a physiologically low peak bone mass, such as in lean but otherwise healthy persons, whereas fractures commonly occur with high-impact trauma, i.e., without bone fragility. Furthermore, low aBMD associated with vitamin D deficiency may be highly prevalent in some regions of the world. Nevertheless, true osteoporosis in the young can occur, which we define as a T-score below −2.5 at spine or hip in association with a chronic disease known to affect bone metabolism. In the absence of secondary causes, the presence of fragility fractures, such as in vertebrae, may point towards genetic or idiopathic osteoporosis. In turn, treatment of the underlying condition may improve bone mass as well. In rare cases, a bone-specific treatment may be indicated, although evidence is scarce for a true benefit on fracture risk. The International Osteoporosis Foundation (IOF) convened a working group to review pathophysiology, diagnosis, and management of osteoporosis in the young, excluding children and adolescents, and provide a screening strategy including laboratory exams for a systematic approach of this condition.
Poor adherence to prescribed treatments is widespread in clinical practice and this can lead to potentially life-threatening events. This problem is apparently very common for osteoporosis treatment ...but the causes of discontinuation and low compliance are complex and poorly defined.
Global adherence to osteoporosis treatment was specifically addressed in a nation-wide survey carried out in 9851 postmenopausal women referred to 141 Italian centres for osteoporosis management for a follow-up assessment, at least one year after having been prescribed a treatment with one of the following drugs: calcium+/-vitamin D supplements alone (CaVitD), hormone replacement therapy (HRT), raloxifene 60 mg (RLX), intramuscular clodronate 100 mg/7-14 days (CLOD), risedronate 5 mg/day (RIS) and alendronate 10mg/daily (ALN10) or 70 mg once weekly (ALN OW).
Overall 19.1% of the patients discontinued the prescribed drug before attending the bone mass re-evaluations, more than half of them within the first 6 months. The discontinuation rate was significantly different between the treatments. The medications most frequently interrupted within one year were CLOD (28.7%; p<0.01 versus any other treatment), while by far the least interrupted was ALN-OW (6.9%; p<0.001 versus any other treatment). The most frequent reasons for discontinuation were drug related side effects, insufficient motivation to treatment and fear of side effects. The prevalence of the reasons for discontinuation were different among treatments: safety concerns were very common for HRT, lack of motivation was the most common cause for CaVitD and CLOD, and drug related side effects for RIS, ALN and RLX. Persistence to treatment was significantly higher in patients with previous vertebral fractures, densitometric osteoporosis, on corticosteroid or anti-inflammatory treatments. A significantly increased risk of treatment interruption was found among patients on benzodiazepine or gastro-protective agents and in patients in whom a bone measurement was not readily available. The highest compliance to recommended dosing was observed with ALN OW and HRT (p<0.001 versus any other) and the lowest for CaVitD (p<0.01 versus any other). Poor treatment compliance (<50% drug taken) was significantly related to benzodiazepine and gastroprotective use, while a significantly better compliance was associated with recognized risk factors for osteoporosis: early menopause, low bone mass values values, previous vertebral fractures. The poorest adherence was observed when treatments were prescribed by General practitioners (GPs), and orthopaedic surgeons (p<0.01 versus global mean).
The results of this large survey of Italian osteoporotic women indicates that the most important determinant of both persistence and compliance to treatment is the type of drug prescribed with a definite advantage of ALN-OW. Treatment compliance is particularly poor for CaVitD and this emphasizes the need for new ways to supplement at least vitamin D. The main reasons for discontinuation are side effects and lack of motivation while the best treatment adherence was observed in patients with severe and well documented osteoporosis.
We present a novel storage-and-access approach for Lagrangian particles in a multiresolution local-timestepping framework for multiphase flow simulations. The proposed method applies a block-particle ...mapping strategy for efficient access of all particles on a specific refinement level while traversing through the multiresolution tree. This allows for extending the local timestepping algorithm with its refinement level-dependent timestep sizes to the evolution of particles, which results in significant speed-up in comparison to standard timestepping. For multi-scale multiphase flow simulations, the particle model is combined with a level-set based multiphase model on a Cartesian grid. To maintain robustness of fluid-state interpolation for particles near the level set-based fluid–fluid interface, WENO-based interpolation is applied which includes both real- and ghost-fluid cells. This enforces the sharp interface property also for interpolated fluid states, and suppresses spurious oscillations in the event of discontinuities.
We validate the particle model with a one-dimensional simulation of a single particle in an air–helium shock tube for one-way coupling, and with two-dimensional simulations of a particle injected in a quiescent domain for the feedback force. Simulations of two-dimensional aerodynamic fragmentation in shear-induced entrainment and Rayleigh–Taylor piercing regimes use Lagrangian particles as sub-grid scale representation of small droplets post-breakup. Finally, three-dimensional massively-parallel simulations of single- and triple-bubble collapse near a wall coated with free-floating particles are presented. The particle cleaning radius of the single-bubble setup agrees reasonably well with experimental reference data. These simulations consider 106 particles and an Eulerian grid with effectively 1012 finite-volume cells at compression rates of more than 90% for the particulate phase. This underlines the advantageous effect of embedding the particles in the multiresolution tree with its spatial and temporal adaptivity, which is necessary for performing such large scale simulations efficiently.
•Efficient multi-scale multiphase framework with multiresolution local-timestepping.•Block-particle mapping for synchronous local integration of particles and cells.•Ghost-fluid based fluid-state interpolation to suppress spurious oscillations.•Massively-parallelized simulations of ultrasound surface cleaning.
•Conservative interface-exchange terms for liquid-solid phase transition.•Semi-implicit level-set approach for improved conservation.•Interface-cut reconstruction including the Stefan ...condition.•WENO-based reconstruction of interface-normal gradients.•Multiresolution scheme with local timestepping for spatial/temporal adaptivity.
The solidification of an undercooled liquid is physically unstable. The dominating instability modes are affected by both the evolving temperature field in the solid and liquid phases, and characteristics of the phase interface such as the curvature and the propagation velocity. To capture the instability mode, therefore both the temperature field and the interface have to be represented accurately in a numerical model of the phase-change process. In this work, we develop conservative interface exchange terms for a sharp-interface formulation of liquid-solid phase transition. Conservation at the interface is maintained by explicit formulation of interface fluxes into both solid and liquid phases. We propose a semi-implicit level-set formulation to evolve the phase interface. A new formulation for the interface surface in a cut cell is derived, which includes the Stefan condition. We achieve low numerical dissipation by an explicit third-order Runge-Kutta scheme for time discretization, and a novel WENO-like (Weighted Essentially Non-Oscillatory) interface-gradient reconstruction. This distinguishes our level-set based sharp-interface model from previous level-set based approaches, which rely on finite-difference based interface treatment, and thus do not ensure discrete conservation at the interface. The flux terms in our approach take into account surface-tension and kinetic effects on the interface temperature (Gibbs-Thomson relation). The Stefan condition provides a relation between interface fluxes of mass and energy, and the interface-propagation velocity. Computational efficiency is maintained by a multiresolution approach for local mesh adaptation, and an adaptive local time-stepping scheme.
We present one- and two-dimensional simulation results for the growth of a planar solidification front and a single parabolic dendrite affected by surface tension. The results agree well with experimental and analytical reference data, showing that the model is capable to capture both stable (planar) and unstable (dendritic-like) growth processes in the heat-diffusion dominated regime. The convergence order for successively finer meshes in the one-dimensional case is one for the interface location and the temperature field, outperforming previously reported level-set based approaches. We present numerical data of a growing crystal with four-fold symmetry. Our results indicate that the artificial dissipation of the underlying numerical scheme affects its capability to reproduce consistently physical tip-splitting instabilities. The proposed low-dissipation scheme is able to resolve such instabilities. Finally, we demonstrate the capability of the method to simulate multiple growing crystals with anisotropic surface-tension and kinetic effects.
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