Transient peak-strain matching partially recovers the age-impaired mechanoadaptive cortical bone response

Mechanoadaptation maintains bone mass and architecture; its failure underlies age-related decline in bone strength. It is unclear whether this is due to failure of osteocytes to sense strain, osteoblasts to form bone or insufficient mechanical stimulus. Mechanoadaptation can be restored to aged bone by surgical neurectomy, suggesting that changes in loading history can rescue mechanoadaptation. We use non-biased, whole-bone tibial analyses, along with characterisation of surface strains and ensuing mechanoadaptive responses in mice at a range of ages, to explore whether sufficient load magnitude can activate mechanoadaptation in aged bone. We find that younger mice adapt when imposed strains are lower than in mature and aged bone. Intriguingly, imposition of short-term, high magnitude loading effectively primes cortical but not trabecular bone of aged mice to respond. This response was regionally-matched to highest strains measured by digital image correlation and to osteocytic mechanoactivation. These data indicate that aged bone’s loading response can be partially recovered, non-invasively by transient, focal high strain regions. Our results indicate that old murine bone does respond to load when the loading is of sufficient magnitude, and bones’ age-related adaptation failure may be due to insufficient mechanical stimulus to trigger mechanoadaptation

Experimental demonstration of a hyper-entangled ten-qubit Schr\"odinger cat state

Coherent manipulation of an increasing number of qubits for the generation of entangled states has been an important goal and benchmark in the emerging field of quantum information science. The multiparticle entangled states serve as physical resources for measurement-based quantum computing and high-precision quantum metrology. However, their experimental preparation has proved extremely challenging. To date, entangled states up to six, eight atoms, or six photonic qubits have been demonstrated. Here, by exploiting both the photons' polarization and momentum degrees of freedom, we report the creation of hyper-entangled six-, eight-, and ten-qubit Schr\"odinger cat states. We characterize the cat states by evaluating their fidelities and detecting the presence of genuine multi-partite entanglement. Small modifications of the experimental setup will allow the generation of various graph states up to ten qubits. Our method provides a shortcut to expand the effective Hilbert space, opening up interesting applications such as quantum-enhanced super-resolving phase measurement, graph-state generation for anyonic simulation and topological error correction, and novel tests of nonlocality with hyper-entanglement.Comment: 11 pages, 5 figures, comments welcom

Interleukin-1 polymorphisms associated with increased risk of gastric cancer

Helicobacter pylori infection is associated with a variety of clinical outcomes including gastric cancer and duodenal ulcer disease. The reasons for this variation are not clear, but the gastric physiological response is influenced by the severity and anatomical distribution of gastritis induced by H. pylori. Thus, individuals with gastritis predominantly localized to the antrum retain normal (or even high) acid secretion, whereas individuals with extensive corpus gastritis develop hypochlorhydria and gastric atrophy, which are presumptive precursors of gastric cancer. Here we report that interleukin-1 gene cluster polymorphisms suspected of enhancing production of interleukin-1-beta are associated with an increased risk of both hypochlorhydria induced by H. pylori and gastric cancer. Two of these polymorphism are in near-complete linkage disequilibrium and one is a TATA-box polymorphism that markedly affects DNA-protein interactions in vitro. The association with disease may be explained by the biological properties of interleukin-1-beta, which is an important pro-inflammatory cytokine and a powerful inhibitor of gastric acid secretion. Host genetic factors that affect interleukin-1-beta may determine why some individuals infected with H. pylori develop gastric cancer while others do no

Observation of eight-photon entanglement

Using ultra-bright sources of pure-state entangled photons from parametric down conversion, an eight-photon interferometer and post-selection detection, we demonstrate the ability to experimentally manipulate eight individual photons and report the creation of an eight-photon Schr\"odinger cat state with an observed fidelity of $0.708 \pm 0.016$.Comment: 6 pages, 4 figure

An Ultrasound Assisted Anchoring Technique (BoneWelding® Technology) for Fixation of Implants to Bone – A Histological Pilot Study in Sheep

The BoneWelding® Technology offers new opportunities to anchor implants within bone. The technology melted the surface of biodegradable polymer pins by means of ultrasound energy to mould material into the structures of the predrilled bone. Temperature changes were measured at the sites of implantation in an in vitro experiment. In the in vivo part of the study two types of implants were implanted in the limb of sheep to investigate the biocompatibility of the method. One implant type was made of PL-DL-lactide (PLA), the second one was a titanium core partially covered with PLA. Healing period was 2 and 6 months, with 3 sheep per group. Bone samples were evaluated radiologically, histologically and histomorphometrically for bone remodeling and inflammatory reactions. Results demonstrated mild and short temperature increase during insertion. New bone formed at the implant without evidence of inflammatory reaction. The amount of adjacent bone was increased compared to normal cancellous bone. It was concluded that the BoneWelding® Technology proved to be a biocompatible technology to anchor biodegradable as well as titanium-PLA implants in bone

Targeted physiotherapy for patellofemoral joint osteoarthritis: A protocol for a randomised, single-blind controlled trial

<p>Abstract</p> <p>Background</p> <p>The patellofemoral joint (PFJ) is one compartment of the knee that is frequently affected by osteoarthritis (OA) and is a potent source of OA symptoms. However, there is a dearth of evidence for compartment-specific treatments for PFJ OA. Therefore, this project aims to evaluate whether a physiotherapy treatment, targeted to the PFJ, results in greater improvements in pain and physical function than a physiotherapy education intervention in people with symptomatic and radiographic PFJ OA.</p> <p>Methods</p> <p>90 people with PFJ OA (PFJ-specific history, signs and symptoms and radiographic evidence of PFJ OA) will be recruited from the community and randomly allocated into one of two treatments. A randomised controlled trial adhering to CONSORT guidelines will evaluate the efficacy of physiotherapy (8 individual sessions over 12 weeks, as well as a home exercise program 4 times/week) compared to a physiotherapist-delivered OA education control treatment (8 individual sessions over 12 weeks). Physiotherapy treatment will consist of (i) quadriceps muscle retraining; (ii) quadriceps and hip muscle strengthening; (iii) patellar taping; (iv) manual PFJ and soft tissue mobilisation; and (v) OA education. Resistance and dosage of exercises will be tailored to the participant's functional level and clinical state. Primary outcomes will be evaluated by a blinded examiner at baseline, 12 weeks and 9 months using validated and reliable pain, physical function and perceived global effect scales. All analyses will be conducted on an intention-to-treat basis using linear mixed regression models, including respective baseline scores as a covariate, subjects as a random effect, treatment condition as a fixed factor and the covariate by treatment interaction.</p> <p>Conclusion</p> <p>This RCT is targeting PFJ OA, an important sub-group of knee OA patients, with a specifically designed conservative intervention. The project's outcome will influence PFJ OA rehabilitation, with the potential to reduce the personal and societal burden of this increasing public health problem.</p> <p>Trial Registration</p> <p>Australia New Zealand Clinical Trials Registry ACTRN12608000288325</p

Sensitivity and Bias in Decision-Making under Risk: Evaluating the Perception of Reward, Its Probability and Value

BACKGROUND: There are few clinical tools that assess decision-making under risk. Tests that characterize sensitivity and bias in decisions between prospects varying in magnitude and probability of gain may provide insights in conditions with anomalous reward-related behaviour. OBJECTIVE: We designed a simple test of how subjects integrate information about the magnitude and the probability of reward, which can determine discriminative thresholds and choice bias in decisions under risk. DESIGN/METHODS: Twenty subjects were required to choose between two explicitly described prospects, one with higher probability but lower magnitude of reward than the other, with the difference in expected value between the two prospects varying from 3 to 23%. RESULTS: Subjects showed a mean threshold sensitivity of 43% difference in expected value. Regarding choice bias, there was a 'risk premium' of 38%, indicating a tendency to choose higher probability over higher reward. An analysis using prospect theory showed that this risk premium is the predicted outcome of hypothesized non-linearities in the subjective perception of reward value and probability. CONCLUSIONS: This simple test provides a robust measure of discriminative value thresholds and biases in decisions under risk. Prospect theory can also make predictions about decisions when subjective perception of reward or probability is anomalous, as may occur in populations with dopaminergic or striatal dysfunction, such as Parkinson's disease and schizophrenia

Time-course of exercise and its association with 12-month bone changes

<p>Abstract</p> <p>Background</p> <p>Exercise has been shown to have positive effects on bone density and strength. However, knowledge of the time-course of exercise and bone changes is scarce due to lack of methods to quantify and qualify daily physical activity in long-term. The aim was to evaluate the association between exercise intensity at 3, 6 and 12 month intervals and 12-month changes in upper femur areal bone mineral density (aBMD) and mid-femur geometry in healthy premenopausal women.</p> <p>Methods</p> <p>Physical activity was continuously assessed with a waist-worn accelerometer in 35 healthy women (35-40 years) participating in progressive high-impact training. To describe exercise intensity, individual average daily numbers of impacts were calculated at five acceleration levels (range 0.3-9.2 <it>g</it>) during time intervals of 0-3, 0-6, and 0-12 months. Proximal femur aBMD was measured with dual x-ray absorptiometry and mid-femur geometry was evaluated with quantitative computed tomography at the baseline and after 12 months. Physical activity data were correlated with yearly changes in bone density and geometry, and adjusted for confounding factors and impacts at later months of the trial using multivariate analysis.</p> <p>Results</p> <p>Femoral neck aBMD changes were significantly correlated with 6 and 12 months' impact activity at high intensity levels (> 3.9 <it>g</it>, <it>r </it>being up to 0.42). Trochanteric aBMD changes were associated even with first three months of exercise exceeding 1.1 <it>g </it>(<it>r </it>= 0.39-0.59, <it>p </it>< 0.05). Similarly, mid-femoral cortical bone geometry changes were related to even first three months' activity (<it>r </it>= 0.38-0.52, <it>p </it>< 0.05). In multivariate analysis, 0-3 months' activity did not correlate with bone change at any site after adjusting for impacts at later months. Instead, 0-6 months' impacts were significant correlates of 12-month changes in femoral neck and trochanter aBMD, mid-femur bone circumference and cortical bone attenuation even after adjustment. No significant correlations were found at the proximal or distal tibia.</p> <p>Conclusion</p> <p>The number of high acceleration impacts during 6 months of training was positively associated with 12-month bone changes at the femoral neck, trochanter and mid-femur. These results can be utilized when designing feasible training programs to prevent bone loss in premenopausal women.</p> <p>Trial registration</p> <p>Clinical trials.gov NCT00697957</p

Functional Relationship between Skull Form and Feeding Mechanics in Sphenodon, and Implications for Diapsid Skull Development

The vertebrate skull evolved to protect the brain and sense organs, but with the appearance of jaws and associated forces there was a remarkable structural diversification. This suggests that the evolution of skull form may be linked to these forces, but an important area of debate is whether bone in the skull is minimised with respect to these forces, or whether skulls are mechanically “over-designed” and constrained by phylogeny and development. Mechanical analysis of diapsid reptile skulls could shed light on this longstanding debate. Compared to those of mammals, the skulls of many extant and extinct diapsids comprise an open framework of fenestrae (window-like openings) separated by bony struts (e.g., lizards, tuatara, dinosaurs and crocodiles), a cranial form thought to be strongly linked to feeding forces. We investigated this link by utilising the powerful engineering approach of multibody dynamics analysis to predict the physiological forces acting on the skull of the diapsid reptile Sphenodon. We then ran a series of structural finite element analyses to assess the correlation between bone strain and skull form. With comprehensive loading we found that the distribution of peak von Mises strains was particularly uniform throughout the skull, although specific regions were dominated by tensile strains while others were dominated by compressive strains. Our analyses suggest that the frame-like skulls of diapsid reptiles are probably optimally formed (mechanically ideal: sufficient strength with the minimal amount of bone) with respect to functional forces; they are efficient in terms of having minimal bone volume, minimal weight, and also minimal energy demands in maintenance