Using the Flow-3D General Moving Object Model to Simulate Coupled Liquid Slosh - Container Dynamics on the SPHERES Slosh Experiment: Aboard the International Space Station

The SPHERES Slosh Experiment (SSE) is a free floating experimental platform developed for the acquisition of long duration liquid slosh data aboard the International Space Station (ISS). The data sets collected will be used to benchmark numerical models to aid in the design of rocket and spacecraft propulsion systems. Utilizing two SPHERES Satellites, the experiment will be moved through different maneuvers designed to induce liquid slosh in the experiment's internal tank. The SSE has a total of twenty-four thrusters to move the experiment. In order to design slosh generating maneuvers, a parametric study with three maneuvers types was conducted using the General Moving Object (GMO) model in Flow-30. The three types of maneuvers are a translation maneuver, a rotation maneuver and a combined rotation translation maneuver. The effectiveness of each maneuver to generate slosh is determined by the deviation of the experiment's trajectory as compared to a dry mass trajectory. To fully capture the effect of liquid re-distribution on experiment trajectory, each thruster is modeled as an independent force point in the Flow-3D simulation. This is accomplished by modifying the total number of independent forces in the GMO model from the standard five to twenty-four. Results demonstrate that the most effective slosh generating maneuvers for all motions occurs when SSE thrusters are producing the highest changes in SSE acceleration. The results also demonstrate that several centimeters of trajectory deviation between the dry and slosh cases occur during the maneuvers; while these deviations seem small, they are measureable by SSE instrumentation

FGF23 - a possible Phosphatonin

Human physiology is dependent on an accurate phosphate (Pi) homeostasis. Defective Pi regulation causes hyper- or hypophosphatemia, which are associated with ectopic calcification or impaired bone mineralization, and a shortened life span. Current endocrine models of Pi homeostasis are incomplete. However, studies of acquired and hereditary disorders of Pi homeostasis have revealed new potential Pi regulating hormones, Phosphatonin(s). One of these is fibroblast growth factor-23 (FGF23). FGF23 is produced in bone and is secreted into the circulation. Mutations in FGF23 causes disturbed Pi regulation, without the appropriate counter-regulatory actions of parathyroid hormone or vitamin D. By the generation of FGF23 transgenic mice, which display phenotypic similarities to patients with hypophosphatemic disorders, we show that FGF23 exerts endocrine actions in the kidney and causes osteomalacia. Renal FGF23 actions severely decrease Pi reabsorption and expression of Klotho, a suggested age suppressor gene, known to be crucial in FGF23 receptor binding and activation. In bone, our transgenic model displays impaired osteoclast polarization, which should be detrimental to osteoclastic bone resorption in osteomalacia. However, in our model osteoclasts efficiently participate in bone matrix degradation. Furthermore, we investigated a large population-based cohort in order to elucidate the role of FGF23 in normal physiology. Importantly, we were able to demonstrate an association of FGF23 to parathyroid hormone, renal function and bone mineral density and we found a correlation of FGF23 to weight and body fat mass. The studies on which this thesis is based, demonstrate that FGF23 has phosphatonin-like properties and that the skeleton functions as an endocrine organ. In addition, the results indicate that FGF23 has a role in bone mineral and lipid metabolism, and that FGF23 is a possible diagnostic marker and therapeutic target for the future

Epidemiology of proximal and diaphyseal humeral fractures in children : an observational study from the Swedish Fracture Register

Background: Most fractures in children are fractures of the upper extremity. Proximal and diaphyseal humeral fractures account for a minority of these fractures. To our knowledge, few previous reports address these fractures. This study aimed to describe the epidemiology and current treatment of proximal and diaphyseal humeral fractures by using the Swedish Fracture Register (SFR). Methods: In this nationwide observational study from the SFR we analysed data on patient characteristics, injury mechanism, fracture classification and treatment. We included patients aged < 16 years at time of injury with proximal or diaphyseal humeral fracture registered in 2015-2019. Results: 1996 (1696 proximal and 300 diaphyseal) fractures were registered. Proximal fractures were more frequent in girls whereas diaphyseal fractures were more frequent in boys. The median age at fracture was 10 years in both fracture types but patient's age was more widespread in diaphyseal fracture (IQR 5-13 compared to IQR 7-12 in proximal). In both sexes, the most registered injury mechanism was fall. Horse-riding was a common mechanism of injury in girls, whereas ice-skating and skiing were common mechanisms in boys. Most proximal fractures were metaphyseal fractures. Most diaphyseal fractures were simple transverse or oblique/spiral fractures. The majority of fractures were treated non-surgically (92% of proximal and 80% of diaphyseal fractures). The treatment method was not associated with the patient's sex. Surgery was more often performed in adolescents. The most common surgical methods were K-wire and cerclage fixation in proximal fracture and intramedullary nailing in diaphyseal fracture. Conclusion: Following falls, we found sex-specific sport activities to cause most proximal and diaphyseal paediatric fractures. Further studies on prophylactic efforts in these activities are needed to investigate whether these fractures are preventable. The majority of the fractures were treated non-surgically, although surgical treatment increased with increasing age in both sexes

Mice expressing a constitutively active PTH/PTHrP receptor in osteoblasts show reduced callus size but normal callus morphology during fracture healing

BACKGROUND: The parathyroid hormone-/parathyroid hormone-related protein (PTH/PTHrP) receptor plays a crucial role in endochondral bone formation and possibly also in fracture healing. Patients with Jansen's metaphysial chondrodysplasia (JMC) have a gain-of-function mutation in the PTH/PTHrP receptor. Transgenic mice expressing JMC PTH/PTHrP receptor mutants in osteoblasts are characterized by increased trabecular bone formation and reduced osteoblastic activity at periosteal sites. We have analyzed the bone phenotype and studied the fracture healing process in this model. METHODS: We performed bone density analysis of tibiae from 17-week-old transgenic mice and controls. Also, tibial fractures were produced in 14-week-old mice. Fracture healing was examined by radiographic and histological analysis. RESULTS: Transgenic mice had a lower total bone mineral content (BMC), by a factor of one-third. The changes were bone compartment-specific with an increase in trabecular bone volume and a decrease in cortical thickness. The calluses in the transgenic mice were smaller, with a reduction in BMC and mean cross-sectional area by a factor of one-half. Despite the smaller size, however, the morphology and progression through the healing process were similar in both transgenic and wild-type littermates. INTERPRETATION: We conclude that the constitutively active PTH/PTHrP receptor has compartment-specific effects on bone formation when expressed in osteoblasts. During fracture healing, however, both the periosteal and the endochondral processes are activated, leading to fracture healing that is temporally and morphologically normal, although the callus tissue is less prominent

Non-invasive tri-modal visualisation via PET/SPECT/μCT of recombinant human bone morphogenetic protein-2 retention and associated bone regeneration : A proof of concept

Bone morphogenetic proteins (BMP's) are vital for bone and cartilage formation, where bone morphogenetic protein-2 (BMP-2) is acknowledged as a growth factor in osteoblast differentiation. However, uncontrolled delivery may result in adverse clinical effects. In this study we investigated the possibility for longitudinal and non-invasive monitoring of implanted [125I]BMP-2 retention and its relation to ossification at the site of implantation. A unilateral critically sized femoral defect was produced in the left limb of rats while the right femur was retained intact as a paired reference control. The defect was filled with a hyaluronan hydrogel with 25% hydroxyapatite alone (carrier control; n = 2) or combined with a mixture of [125I]BMP-2 (150 μg/ml; n = 4). Bone formation was monitored using micro computed tomography (μCT) scans at 1, 3, 5, 7, 9 and 12 weeks. The retention of [125I]BMP-2 was assessed with single photon emission computed tomography (SPECT), and the bone healing process was followed with sodium fluoride (Na18F) using positron emission tomography (PET) at day 3 and at week 2, 4, and 6. A rapid burst release of [125I]BMP-2 was detected via SPECT. This was followed by a progressive increase in uptake levels of [18F]fluoride depicted by PET imaging that was confirmed as bone formation via μCT. We propose that this functional, non-invasive imaging method allows tri-modal visualisation of the release of BMP-2 and the following in vivo response. We suggest that the potential of this novel technique could be considered for preclinical evaluation of novel smart materials on bone regeneration.G. Hulsart-Billström and R. K. Selvaraju contributed equally to this work and should be regarded as joint first authors.</p

Fibroblast growth factor-23 is associated with parathyroid hormone and renal function in a population-based cohort of elderly men

Objective: Fibroblast growth factor-23 (FGF23) is a circulating factor involved in phosphate (Pi) and vitamin D metabolism. Serum FGF23 is increased at later stages of chronic kidney disease due to chronic hyperphosphatemia and decreased renal clearance. Recent studies also indicate that FGF23 may directly regulate the expression of parathyroid hormone (PTH) in vitro. Therefore, the objective of the current study was to determine the relationship between FGF23, PTH, and other biochemistries in vivo in subjects with no history of renal disease. Design: Serum biochemistries were measured in a subsample of the population-based Swedish part of the MrOS study In total, 1000 Caucasian men aged 70-80 years were randomly selected from the population. Methods: Intact FGF23, Pi, calcium, albumin, estimated glomerular filtration rate (eGFR, calculated from cystatin C), PTH, and 25(OH)D-3 were measured. Association studies were performed using linear univariate and multivariate regression analyses. Results: The median FGF23 level was 36.6 pg/ml, ranging from 0.63 to 957 pg/ml. There was a significant correlation between log FGF23 and eGFR (r=-0.21; P 60 ml/min. Only eGFR (beta = 0.35; P < 0.0001.) remained as a predictor of log FGF23 in subjects with eGFR < 60 ml/min. Conclusions: Serum FGF23 and PTH are associated in vivo, supporting recent findings that FGF23 directly regulates PTH expression in vitro. Additionally, eGFR is associated with FGF23 in subjects with normal or mildly impaired renal function, indicating that GFR may modulate FGF23 levels independent of serum Pi

Circulating Fibroblast Growth Factor-23 Is Associated With Fat Mass and Dyslipidemia in Two Independent Cohorts of Elderly Individuals

Objective-Disturbances in mineral metabolism define an increased cardiovascular risk in patients with chronic kidney disease. Fibroblast growth factor-23 (FGF23) is a circulating regulator of phosphate and vitamin D metabolism and has recently been implicated as a putative pathogenic factor in cardiovascular disease. Because other members of the FGF family play a role in lipid and glucose metabolism, we hypothesized that FGF23 would associate with metabolic factors that predispose to an increased cardiovascular risk. The goal of this study was to investigate the relationship between FGF23 and metabolic cardiovascular risk factors in the community. Methods and Results-Relationships between serum FGF23 and body mass index (BMI), waist circumference, waist-to-hip ratio, serum lipids, and fat mass were examined in 2 community-based, cross-sectional cohorts of elderly whites (Osteoporotic Fractures in Men Study: 964 men aged 75 +/- 3.2; Prospective Investigation of the Vasculature in Uppsala Seniors study: 946 men and women aged 70). In both cohorts, FGF23 associated negatively with high-density lipoprotein and apolipoprotein A1 (7% to 21% decrease per 1-SD increase in log FGF23; P < 0.01) and positively with triglycerides (11% to 14% per 1-SD increase in log FGF23; P < 0.01). A 1-SD increase in log FGF23 was associated with a 7% to 20% increase in BMI, waist circumference, and waist-to-hip ratio and a 7% to 18% increase in trunk and total body fat mass (P < 0.01) as determined by whole-body dual x-ray absorptiometry. FGF23 levels were higher in subjects with the metabolic syndrome compared with those without (46.4 versus 41.2 pg/ mL; P < 0.05) and associated with an increased risk of having the metabolic syndrome (OR per 1-SD increase in log FGF23, 1.21; 95% CI, 1.04 to 1.40; P < 0.05). Conclusion-We report for the first time on associations between circulating FGF23, fat mass, and adverse lipid metabolism resembling the metabolic syndrome, potentially representing a novel pathway(s) linking high FGF23 to an increased cardiovascular risk. (Arterioscler Thromb Vasc Biol. 2011;31:219-227.