Extracellular ATP released by osteoblasts is a key local inhibitor of bone mineralisation

Previous studies have shown that exogenous ATP (>1µM) prevents bone formation in vitro by blocking mineralisation of the collagenous matrix. This effect is thought to be mediated via both P2 receptor-dependent pathways and a receptor-independent mechanism (hydrolysis of ATP to produce the mineralisation inhibitor pyrophosphate, PPi). Osteoblasts are also known to release ATP constitutively. To determine whether this endogenous ATP might exert significant biological effects, bone-forming primary rat osteoblasts were cultured with 0.5-2.5U/ml apyrase (which sequentially hydrolyses ATP to ADP to AMP + 2Pi). Addition of 0.5U/ml apyrase to osteoblast culture medium degraded extracellular ATP to <1% of control levels within 2 minutes; continuous exposure to apyrase maintained this inhibition for up to 14 days. Apyrase treatment for the first 72 hours of culture caused small decreases (≤25%) in osteoblast number, suggesting a role for endogenous ATP in stimulating cell proliferation. Continuous apyrase treatment for 14 days (≥0.5U/ml) increased mineralisation of bone nodules by up to 3-fold. Increases in bone mineralisation were also seen when osteoblasts were cultured with the ATP release inhibitors, NEM and brefeldin A, as well as with P2X1 and P2X7 receptor antagonists. Apyrase decreased alkaline phosphatase (TNAP) activity by up to 60%, whilst increasing the activity of the PPi-generating ecto-nucleotide pyrophosphatase/phosphodiesterases (NPPs) up to 2.7-fold. Both collagen production and adipocyte formation were unaffected. These data suggest that nucleotides released by osteoblasts in bone could act locally, via multiple mechanisms, to limit mineralisation

Estimating Sensitivity of Laboratory Testing for Influenza in Canada through Modelling

Background: The weekly proportion of laboratory tests that are positive for influenza is used in public health surveillance systems to identify periods of influenza activity. We aimed to estimate the sensitivity of influenza testing in Canada based on results of a national respiratory virus surveillance system. Methods and Findings: The weekly number of influenza-negative tests from 1999 to 2006 was modelled as a function of laboratory-confirmed positive tests for influenza, respiratory syncytial virus (RSV), adenovirus and parainfluenza viruses, seasonality, and trend using Poisson regression. Sensitivity was calculated as the number of influenza positive tests divided by the number of influenza positive tests plus the model-estimated number of false negative tests. The sensitivity of influenza testing was estimated to be 33 % (95%CI 32–34%), varying from 30–40 % depending on the season and region. Conclusions: The estimated sensitivity of influenza tests reported to this national laboratory surveillance system is considerably less than reported test characteristics for most laboratory tests. A number of factors may explain this difference, including sample quality and specimen procurement issues as well as test characteristics. Improved diagnosis would permit better estimation of the burden of influenza

Strengthening of short splices in RC beams using Post-Tensioned Metal Straps

This paper investigates the effectiveness of a novel and cost-effective strengthening technique using Post-Tensioned Metal Straps (PTMS) at enhancing the bond behaviour of short lap spliced steel bars in reinforced concrete (RC) beams. Twelve RC beams with a short lap splice length of 10d b (d b = bar diameter) at the midspan zone were tested in flexure to examine the bond splitting failure. The effect of confinement (no confinement, internal steel stirrups or external PTMS), bar diameter and concrete cover were examined. The results show that, whilst unconfined control beams failed prematurely due to cover splitting, the use of PTMS confinement enhanced the bond strength of the spliced bars by up to 58 % and resulted in a less brittle behaviour. Based on the test results, a new analytical model is proposed to predict the additional bond strength provided by PTMS confinement. The model should prove useful in the strengthening design of substandard lap spliced RC elements

Climate model forecast biases assessed with a perturbed physics ensemble

Perturbed physics ensembles have often been used to analyse long-timescale climate model behaviour, but have been used less often to study model processes on shorter timescales. We combine a transient perturbed physics ensemble with a set of initialised forecasts to deduce regional process errors present in the standard HadCM3 model, which cause the model to drift in the early stages of the forecast. First, it is shown that the transient drifts in the perturbed physics ensembles can be used to recover quantitatively the parameters that were perturbed. The parameters which exert most influence on the drifts vary regionally, but upper ocean mixing and atmospheric convective processes are particularly important on the 1-month timescale. Drifts in the initialised forecasts are then used to recover the ‘equivalent parameter perturbations’, which allow identification of the physical processes that may be at fault in the HadCM3 representation of the real world. Most parameters show positive and negative adjustments in different regions, indicating that standard HadCM3 values represent a global compromise. The method is verified by correcting an unusually widespread positive bias in the strength of wind-driven ocean mixing, with forecast drifts reduced in a large number of areas as a result. This method could therefore be used to improve the skill of initialised climate model forecasts by reducing model biases through regional adjustments to physical processes, either by tuning or targeted parametrisation refinement. Further, such regionally tuned models might also significantly outperform standard climate models, with global parameter configurations, in longer-term climate studies

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

Effects of Aluminum Oxide Nanoparticles on the Growth, Development, and microRNA Expression of Tobacco (Nicotiana tabacum)

Nanoparticles are a class of newly emerging environmental pollutions. To date, few experiments have been conducted to investigate the effect nanoparticles may have on plant growth and development. It is important to study the effects nanoparticles have on plants because they are stationary organisms that cannot move away from environmental stresses like animals can, therefore they must overcome these stresses by molecular routes such as altering gene expression. microRNAs (miRNA) are a newly discovered, endogenous class of post-transcriptional gene regulators that function to alter gene expression by either targeting mRNAs for degradation or inhibiting mRNAs translating into proteins. miRNAs have been shown to mediate abiotic stress responses such as drought and salinity in plants by altering gene expression, however no study has been performed on the effect of nanoparticles on the miRNA expression profile; therefore our aim in this study was to classify if certain miRNAs play a role in plant response to Al2O3 nanoparticle stress. In this study, we exposed tobacco (Nicotiana tabacum) plants (an important cash crop as well as a model organism) to 0%, 0.1%, 0.5%, and 1% Al2O3 nanoparticles and found that as exposure to the nanoparticles increased, the average root length, the average biomass, and the leaf count of the seedlings significantly decreased. We also found that miR395, miR397, miR398, and miR399 showed an extreme increase in expression during exposure to 1% Al2O3 nanoparticles as compared to the other treatments and the control, therefore these miRNAs may play a key role in mediating plant stress responses to nanoparticle stress in the environment. The results of this study show that Al2O3 nanoparticles have a negative effect on the growth and development of tobacco seedlings and that miRNAs may play a role in the ability of plants to withstand stress to Al2O3 nanoparticles in the environment

Patient involvement in medical decision-making and pain among elders: physician or patient-driven?

BACKGROUND: Pain is highly prevalent among older adults, but little is known about how patient involvement in medical decision-making may play a role in limiting its occurrence or severity. The purpose of this study was to evaluate whether physician-driven and patient-driven participation in decision-making were associated with the odds of frequent and severe pain. METHODS: A cross-sectional population-based survey of 3,135 persons age 65 and older was conducted in the 108-county region comprising West Texas. The survey included self-reports of frequent pain and, among those with frequent pain, the severity of pain. RESULTS: Findings from multivariate logistic regression analyses showed that higher patient-driven participation in decision-making was associated with lower odds (OR, 0.82; 95% CI, 0.75–0.89) of frequent pain, but was not significantly associated with severe pain. Physician-driven participation was not significantly associated with frequent or severe pain. CONCLUSIONS: The findings suggest that patients may need to initiate involvement in medical decision-making to reduce their chances of experiencing frequent pain. Changes to other modifiable health care characteristics, including access to a personal doctor and health insurance coverage, may be more conducive to limiting the risk of severe pain

The Emotional and Attentional Impact of Exposure to One's Own Body in Bulimia Nervosa: A Physiological View

Background: Body dissatisfaction is the most relevant body image disturbance in bulimia nervosa (BN). Research has shown that viewing one's own body evokes negative thoughts and emotions in individuals with BN. However, the psychophysiological mechanisms involved in this negative reaction have not yet been clearly established. Our aim was to examine the emotional and attentional processes that are activated when patients with BN view their own bodies. Method: We examined the effects of viewing a video of one's own body on the physiological (eye-blink startle, cardiac defense, and skin conductance) and subjective (pleasure, arousal, and control ratings) responses elicited by a burst of 110 dB white noise of 500 ms duration. The participants were 30 women with BN and 30 healthy control women. The experimental task consisted of two consecutive and counterbalanced presentations of the auditory stimulus preceded, alternatively, by a video of the participant's own body versus no such video. Results: The results showed that, when viewing their own bodies, women with BN experienced (a) greater inhibition of the startle reflex, (b) greater cardiac acceleration in the first component of the defense reaction, (c) greater skin conductance response, and (d) less subjective pleasure and control combined with greater arousal, compared with the control participants. Conclusion: Our findings suggest that, for women with BN, peripheral-physiological responses to self-images are dominated by attentional processes, which provoke an immobility reaction caused by a dysfunctional negative response to their own body.The present research was supported by grants from the Spanish Ministry of Economy and Competitiveness [PSI2009-08417 and PSI2012-31395]. P.P. was supported by grants from the Spanish Ministry of Science and Innovation and University Jaume I [ECO2011-23634, P1-1B2012-27, and JCI-2010-06790]