Risedronate in adults with osteogenesis imperfecta type I: Increased bone mineral density and decreased bone turnover, but high fracture rate persists

Summary Bisphosphonates can increase bone mineral density (BMD) in children with osteogenesis imperfecta (OI). In this study of adults with OI type I, risedronate increased BMD at lumbar spine (but not total hip) and decreased bone turnover. However, the fracture rate in these patients remained high. Introduction Intravenous bisphosphonates given to children with OI can increase BMD and reduce fracture incidence. Oral and/or intravenous bisphosphonates may have similar effects in adults with OI. We completed an observational study of the effect of risedronate in adults with OI type I. Methods Thirty-two adults (mean age, 39 years) with OI type I were treated with risedronate (total dose, 35 mg weekly) for 24 months. Primary outcome measures were BMD changes at lumbar spine (LS) and total hip (TH). Secondary outcome measures were fracture incidence, bone pain, and change in bone turnover markers (serum procollagen type I aminopropeptide (P1NP) and bone ALP). A meta-analysis of published studies of oral bisphosphonates in adults and children with OI was performed. Results Twenty-seven participants (ten males and seventeen females) completed the study. BMD increased at LS by 3.9% (0.815 vs. 0.846 g/cm 2, p=0.007; mean Z-score, -1.93 vs. -1.58, p=0.002), with no significant change at TH. P1NP fell by 37% (p=0.00041), with no significant change in bone ALP (p=0.15). Bone pain did not change significantly (p=0.6). Fracture incidence remained high, with 25 clinical fractures and 10 major fractures in fourteen participants (0.18 major fractures per person per year), with historical data of 0.12 fractures per person per year. The meta-analysis did not demonstrate a significant difference in fracture incidence in patients with OI treated with oral bisphosphonates. Conclusions Risedronate in adults with OI type I results in modest but significant increases in BMD at LS, and decreased bone turnover. However, this may be insufficient to make a clinically significant difference to fracture incidence.

Comparison of measured sleeping metabolic rate and predicted basal metabolic rate during the first year of life : evidence of a bias changing with increasing metabolic rate

Objective: To compare measurements of sleeping metabolic rate (SMR) in infancy with predicted basal metabolic rate (BMR) estimated by the equations of Schofield. Methods: Some 104 serial measurements of SMR by indirect calorimetry were performed in 43 healthy infants at 1.5, 3, 6, 9 and 12 months of age. Predicted BMR was calculated using the weight only (BMR-wo) and weight and height (BMR-wh) equations of Schofield for 0-3-y-olds. Measured SMR values were compared with both predictive values by means of the Bland-Altman statistical test. Results: The mean measured SMR was 1.48 MJ/day. The mean predicted BMR values were 1.66 and 1.47 MJ/day for the weight only and weight and height equations, respectively. The Bland-Altman analysis showed that BMR-wo equation on average overestimated SMR by 0.18 MJ/day (11%) and the BMR-wh equation underestimated SMR by 0.01 MJ/day (1%). However the 95% limits of agreement were wide: -0.64 to + 0.28 MJ/day (28%) for the former equation and -0.39 to + 0.41 MJ/day (27%) for the latter equation. Moreover there was a significant correlation between the mean of the measured and predicted metabolic rate and the difference between them. Conclusions: The wide variation seen in the difference between measured and predicted metabolic rate and the bias probably with age indicates there is a need to measure actual metabolic rate for individual clinical care in this age group.

MRI-based strain and strain rate analysis of left ventricle: A modified hierarchical transformation model

Background Different from other indicators of cardiac function, such as ejection fraction and transmitral early diastolic velocity, myocardial strain is promising to capture subtle alterations that result from early diseases of the myocardium. In order to extract the left ventricle (LV) myocardial strain and strain rate from cardiac cine-MRI, a modified hierarchical transformation model was proposed. Methods A hierarchical transformation model including the global and local LV deformations was employed to analyze the strain and strain rate of the left ventricle by cine-MRI image registration. The endocardial and epicardial contour information was introduced to enhance the registration accuracy by combining the original hierarchical algorithm with an Iterative Closest Points using Invariant Features algorithm. The hierarchical model was validated by a normal volunteer first and then applied to two clinical cases (i.e., the normal volunteer and a diabetic patient) to evaluate their respective function. Results Based on the two clinical cases, by comparing the displacement fields of two selected landmarks in the normal volunteer, the proposed method showed a better performance than the original or unmodified model. Meanwhile, the comparison of the radial strain between the volunteer and patient demonstrated their apparent functional difference. Conclusions The present method could be used to estimate the LV myocardial strain and strain rate during a cardiac cycle and thus to quantify the analysis of the LV motion function.

In vivo velocity vector imaging and time-resolved strain rate measurements in the wall of blood vessels using MRI

In this paper, we present a new approach for velocity vector imaging and time-resolved measurements of strain rates in the wall of human arteries using MRI and we prove its feasibility on two examples: in vitro on a phantom and in vivo on the carotid artery of a human subject. Results point out the promising potential of this approach for investigating the mechanics of arterial tissues in vivo.

Rapid assessment of genotype-by-environment interactions and heritability for growth rate in aquaculture species using in vitro fertilisation and DNA tagging

Commercial environments may receive only a fraction of expected genetic gains for growth rate as predicted from the selection environment This fraction is the result of undesirable genotype-by-environment interactions (G x E) and measured by the genetic correlation (r(g)) of growth between environments. Rapid estimates of genetic correlation achieved in one generation are notoriously difficult to estimate with precision. A new design is proposed where genetic correlations can be estimated by utilising artificial mating from cryopreserved semen and unfertilised eggs stripped from a single female. We compare a traditional phenotype analysis of growth to a threshold model where only the largest fish are genotyped for sire identification. The threshold model was robust to differences in family mortality differing up to 30%. The design is unique as it negates potential re-ranking of families caused by an interaction between common maternal environmental effects and growing environment. The design is suitable for rapid assessment of G x E over one generation with a true 0.70 genetic correlation yielding standard errors as low as 0.07. Different design scenarios were tested for bias and accuracy with a range of heritability values, number of half-sib families created, number of progeny within each full-sib family, number of fish genotyped, number of fish stocked, differing family survival rates and at various simulated genetic correlation levels

Bayesian designs with frequentist and Bayesian error rate considerations

So far, most Phase II trials have been designed and analysed under a frequentist framework. Under this framework, a trial is designed so that the overall Type I and Type II errors of the trial are controlled at some desired levels. Recently, a number of articles have advocated the use of Bavesian designs in practice. Under a Bayesian framework, a trial is designed so that the trial stops when the posterior probability of treatment is within certain prespecified thresholds. In this article, we argue that trials under a Bayesian framework can also be designed to control frequentist error rates. We introduce a Bayesian version of Simon's well-known two-stage design to achieve this goal. We also consider two other errors, which are called Bayesian errors in this article because of their similarities to posterior probabilities. We show that our method can also control these Bayesian-type errors. We compare our method with other recent Bayesian designs in a numerical study and discuss implications of different designs on error rates. An example of a clinical trial for patients with nasopharyngeal carcinoma is used to illustrate differences of the different designs.

Modelling growth rate of Penaeus monodon Fabricius in intensively managed ponds: effects of temperature, pond age and stocking density

Records of shrimp growth and water quality made during 12 crops from each of 48 ponds, over a period of 6.5 years, were provided by a Queensland, Australia, commercial shrimp farm, These data were analysed with a new growth model derived from the Gompertz model. The results indicate that water temperature, mortality and pond age significantly affect growth rates. After 180 days, shrimp reach 34 g at constant 30 degrees C, but only 15 g after the same amount of time at 20 degrees C. Mortality, through thinning the density of shrimp in the ponds, increased the growth rate, but the effect is small. With continual production, growth rates at first remained steady, then appeared to decrease for the sixth and seventh crop, after which they have increased steadily with each crop. It appears that conservative pond management, together with a gradual improvement in husbandry techniques, particularly feed management, brought about this change. This has encouraging implications for the long-term sustainability of the farming methods used. The growth model can be used to predict productivity, and hence, profitability, of new aquaculture locations or new production strategies.

Development and Simulation of a Variable Rate Controller for an Air search and Air Sampling Unmanned Aerial System

This report describes the development and simulation of a variable rate controller for a 6-degree of freedom nonlinear model. The variable rate simulation model represents an off the shelf autopilot. Flight experiment involves risks and can be expensive. Therefore a dynamic model to understand the performance characteristics of the UAS in mission simulation before actual flight test or to obtain parameters needed for the flight is important. The control and guidance is implemented in Simulink. The report tests the use of the model for air search and air sampling path planning. A GUI in which a set of mission scenarios, in which two experts (mission expert, i.e. air sampling or air search and an UAV expert) interact, is presented showing the benefits of the method.

Miniscleral lens wear influences corneal curvature and optics

Purpose Transient changes in corneal topography associated with soft and conventional or reverse geometry rigid contact lens wear have been well documented; however, only a few studies have examined the influence of scleral contact lens wear upon the cornea. Therefore, in this study, we examined the influence of modern miniscleral contact lenses, which land entirely on the sclera and overlying tissues, upon anterior corneal curvature and optics. Methods Anterior corneal topography and elevation data were acquired using Scheimpflug imaging (Pentacam HR, Oculus) immediately prior to and following 8 hours of miniscleral contact lens wear in 15 young healthy adults (mean age 22 ± 3 years, 8 East Asian, 7 Caucasian) with normal corneae. Corneal diurnal variations were accounted for using data collected on a dedicated measurement day without contact lens wear. Corneal clearance was quantified using an optical coherence tomographer (RS-3000, Nidek) following lens insertion and after 8 hours of lens wear. Results Although corneal clearance was maintained throughout the 8 hour lens wear period, significant corneal flattening (up to 0.08 ± 0.04 mm) was observed, primarily in the superior mid-peripheral cornea, which resulted in a slight increase in against-the-rule corneal astigmatism (mean +0.02/-0.15 x 94 for an 8 mm diameter). Higher order aberration terms of horizontal coma, vertical coma and spherical aberration all underwent significant changes for an 8 mm corneal diameter (p ≤ 0.01), which typically resulted in a decrease in RMS error values (mean change in total higher order RMS -0.035 ± 0.046 µm for an 8 mm diameter). There was no association between the magnitude of change in central or mid-peripheral corneal clearance during lens wear and the observed changes in corneal curvature (p > 0.05). However, Asian participants displayed a significantly greater reduction in corneal clearance (p = 0.04) and greater superior-nasal corneal flattening compared to Caucasians (p = 0.048). Conclusions Miniscleral contact lenses that vault the cornea induce significant changes in anterior corneal surface topography and higher order aberrations following 8 hours of lens wear. The region of greatest corneal flattening was observed in the superior-nasal mid-periphery, more so in Asian participants. Practitioners should be aware that corneal measurements obtained following miniscleral lens removal may mask underlying corneal steepening.

Hypoxic corneal changes following 8 hours of scleral contact lens wear

- Purpose To examine the change in corneal thickness and posterior curvature following 8 hours of miniscleral contact lens wear. - Methods Scheimpflug imaging (Pentacam HR, Oculus) was captured before, and immediately following, 8 hours of miniscleral contact lens wear for 15 young (mean age 22 ± 3 years), healthy participants with normal corneae. Natural diurnal variations were considered by measuring baseline corneal changes obtained on a separate control day without contact lens wear. - Results Over the central 6 mm of the cornea, a small, but highly statistically significant amount of edema was observed following 8 hours of miniscleral lens wear, after accounting for normal diurnal fluctuations (mean ± standard deviation percentage swelling 1.70 ± 0.98%, p < 0.0001). Posterior corneal topography remained stable following lens wear (-0.01 ± 0.07 mm steepening over the central 6 mm, p = 0.60). The magnitude of posterior corneal topographical changes following lens wear did not correlate with the extent of lens-related corneal edema (r = -0.16, p = 0.57). Similarly, the initial central corneal vault (maximum post-lens tear layer depth) was not associated with corneal swelling following lens removal (r = 0.27, p = 0.33). - Conclusions While a small amount of corneal swelling was induced following 8 hours of miniscleral lens wear (on average <2%), modern high Dk miniscleral contact lenses that vault the cornea do not induce clinically significant corneal edema or hypoxic related posterior corneal curvature changes during short-term wear. Longer-term studies of compromised eyes (e.g. corneal ectasia) are still required to inform the optimum lens and fitting characteristics for safe scleral lens wear to minimize corneal hypoxia.

Estimating cell diffusivity and cell proliferation rate by interpreting IncuCyte ZOOM™ assay data using the Fisher-Kolmogorov model

Background: Standard methods for quantifying IncuCyte ZOOM™ assays involve measurements that quantify how rapidly the initially-vacant area becomes re-colonised with cells as a function of time. Unfortunately, these measurements give no insight into the details of the cellular-level mechanisms acting to close the initially-vacant area. We provide an alternative method enabling us to quantify the role of cell motility and cell proliferation separately. To achieve this we calibrate standard data available from IncuCyte ZOOM™ images to the solution of the Fisher-Kolmogorov model. Results: The Fisher-Kolmogorov model is a reaction-diffusion equation that has been used to describe collective cell spreading driven by cell migration, characterised by a cell diffusivity, D, and carrying capacity limited proliferation with proliferation rate, λ, and carrying capacity density, K. By analysing temporal changes in cell density in several subregions located well-behind the initial position of the leading edge we estimate λ and K. Given these estimates, we then apply automatic leading edge detection algorithms to the images produced by the IncuCyte ZOOM™ assay and match this data with a numerical solution of the Fisher-Kolmogorov equation to provide an estimate of D. We demonstrate this method by applying it to interpret a suite of IncuCyte ZOOM™ assays using PC-3 prostate cancer cells and obtain estimates of D, λ and K. Comparing estimates of D, λ and K for a control assay with estimates of D, λ and K for assays where epidermal growth factor (EGF) is applied in varying concentrations confirms that EGF enhances the rate of scratch closure and that this stimulation is driven by an increase in D and λ, whereas K is relatively unaffected by EGF. Conclusions: Our approach for estimating D, λ and K from an IncuCyte ZOOM™ assay provides more detail about cellular-level behaviour than standard methods for analysing these assays. In particular, our approach can be used to quantify the balance of cell migration and cell proliferation and, as we demonstrate, allow us to quantify how the addition of growth factors affects these processes individually.

Assessment of the underreporting rate of death cause data in Shandong province using capture-mark-recapture method [应用捕获再捕获方法评估山东省死因登记漏报率水平]

To evaluate the underreporting rate of death -cause data in Shandong province during 2012 to 2013 by capture -mark -recapture method and to provide the base for health strategy. Methods All counties were divided into 5 stratifications according the death rates of 2012, and 14 counties were selected, then 3 towns or streets were selected in each country, 10 villages or neighborhood committees were selected in each town （street）. The death data collected from security bureau and civil affairs bureau were compared with the reporting death data from the National Cause of Death Surveillance, and the underreporting rate was calculated. Results In present study, 6 929 death cases were collected, it was found that 1 556 cases were underreported. The death cases estimated by CMR method were 6 227 cases （95%CI: 7 593-7 651）, and the average underreporting rate was 23.15%. There were significantly differences between different stratifications （P<0.01）. The underreporting rate in 0-4 years old group was 56.93%, the male underreporting rate was 22.31% and the female underreporting rate was 24.09%. There was no significant difference between male and female groups （P>0.05）. Conclusion There is an obvious underreport in the cause of death surveillance of Shandong province, and the underreporting rates are different among the 5 stratifications. The underreporting rate is higher in 0-4 years old group, and the investigation of the death cause surveillance for young residents is not perfect in some countries. The investigation quality of the death cause surveillance should be improved, increasing the integrity of the report data and adjusting the mortalities in different stratifications for obtaining a accurate mortality in Shandong province.

Rate capability of graphite materials as negative electrodes in lithium-ion capacitors

The lithium-ion exchange rate capability of various commercial graphite materials are evaluated using galvanostatic charge/discharge cycling in a half-cell configuration over a wide range of C-rates (0.1 similar to 60C). The results confirm that graphite is capable of de-intercalating stored charge at high rates, but has a poor intercalating rate capability. Decreasing the graphite coating thickness leads to a limited rate performance improvement of the electrode. Reducing the graphite particle size shows enhanced C-rate capability but with increased irreversible capacity loss (ICL). It is demonstrated that the rate of intercalation of lithium-ions into the graphite is significantly limited compared with the corresponding rate of de-intercalation at high C-rates. For the successful utilisation of commercially available conventional graphite as a negative electrode in a lithium-ion capacitor (LIC), its intercalation rate capability needs to be improved or oversized to accommodate high charge rates.

Morphological changes in the conjunctiva, episclera and sclera following short-term miniscleral contact lens wear in rigid lens neophytes

PURPOSE To quantify the influence of short-term wear of miniscleral contact lenses on the morphology of the corneo-scleral limbus, the conjunctiva, episclera and sclera. METHODS OCT images of the anterior eye were captured before, immediately following 3h of wear and then 3h after removal of a miniscleral contact lens for 10 young (27±5 years) healthy participants (neophyte rigid lens wearers). The region of analysis encompassed 1mm anterior, to 3.5mm posterior to the scleral spur. Natural diurnal variations in thickness were measured on a separate day and compensated for in subsequent analyses. RESULTS Following 3h of lens wear, statistically significant tissue thinning was observed across all quadrants, with a mean decrease in thickness of -24.1±3.6μm (p<0.001), which diminished, but did not return to baseline 3h after lens removal (-16.9±1.9μm, p<0.001). The largest tissue compression was observed in the superior quadrant (-49.9±8.5μm, p<0.01) and in the annular zone 1.5mm from the scleral spur (-48.2±5.7μm), corresponding to the approximate edge of the lens landing zone. Compression of the conjunctiva/episclera accounted for about 70% of the changes. CONCLUSIONS Optimal fitting miniscleral contact lenses worn for three hours resulted in significant tissue compression in young healthy eyes, with the greatest thinning observed superiorly, potentially due to the additional force of the eyelid, with a partial recovery of compression 3h after lens removal. Most of the morphological changes occur in the conjunctiva/episclera layers.

Experimental and numerical investigation of strain-rate-dependent behavior of kangaroo shoulder cartilage

This thesis introduces a new animal model, kangaroo, to biomechanical investigations of shoulder cartilage research. It examines the effect of cartilage structure and constituents on tissue behavior and its adaptation to mechanical loading. In doing so, the study explains the relationship of tissue's functional behaviors to its structure and constituents which has important implications for tissue engineering strategies catering joint specific cartilage tissue generation.