Allogeneic morphogenetic protein vs. recombinant human bone morphogenetic protein-2 in lumbar interbody fusion procedures: a radiographic and economic analysis

BACKGROUND: Since the introduction of rhBMP-2 (Infuse®) in 2002, surgeons have had an alternative substitute to autograft and its related donor site morbidity. Recently, the prevalence of reported adverse events and complications related to the use of rhBMP-2 has raised many ethical and legal concerns for surgeons. Additionally, the cost and decreasing reimbursement landscape of rhBMP-2 use have required identification of a viable alternative. Osteo allogeneic morphogenetic protein (OsteoAMP®) is a commercially available allograft-derived growth factor rich in osteoinductive, angiogenic, and mitogenic proteins. This study compares the radiographic fusion outcomes between rhBMP-2 and OsteoAMP allogeneic morphogenetic protein in lumbar interbody fusion spine procedures. METHODS: Three hundred twenty-one (321) patients from three centers underwent a transforaminal lumbar interbody fusion (TLIF) or lateral lumbar interbody fusion (LLIF) procedure and were assessed by an independent radiologist for fusion and radiographically evident complications. The independent radiologist was blinded to the intervention, product, and surgeon information. Two hundred and twenty-six (226) patients received OsteoAMP with autologous local bone, while ninety-five (95) patients received Infuse with autologous local bone. Patients underwent radiographs (x-ray and/or CT) at standard postoperative follow-up intervals of approximately 1, 3, 6, 12, and 18 months. Fusion was defined as radiographic evidence of bridging across endplates, or bridging from endplates to interspace disc plugs. Osteobiologic surgical supply costs were also analyzed to ascertain cost differences between OsteoAMP and rhBMP-2. RESULTS: OsteoAMP produced higher rates of fusion at 6, 12, and 18 months (p ≤ 0.01). The time required for OsteoAMP to achieve fusion was approximately 40% less than rhBMP-2 with approximately 70% fewer complications. Osteobiologic supply costs were 80.5% lower for OsteoAMP patients (73.7% lower per level) than for rhBMP-2. CONCLUSIONS: Results of this study indicate that OsteoAMP is a viable alternative to rhBMP-2 both clinically and economically when used in TLIF and LLIF spine procedures

Risk factors for Nipah virus infection among pteropid bats, Peninsular Malaysia

We conducted cross-sectional and longitudinal studies to determine the distribution of and risk factors for seropositivity to Nipah virus (NiV) among Pteropus vampyrus and P. hypomelanus bats in Peninsular Malaysia. Neutralizing antibodies against NiV were detected at most locations surveyed. We observed a consistently higher NiV risk (odds ratio 3.9) and seroprevalence (32.8%) for P. vampyrus than P. hypomelanus (11.1%) bats. A 3-year longitudinal study of P. hypomelanus bats indicated nonseasonal temporal variation in seroprevalence, evidence for viral circulation within the study period, and an overall NiV seroprevalence of 9.8%. The seroprevalence fluctuated over the study duration between 1% and 20% and generally decreased during 2004–2006. Adult bats, particularly pregnant, with dependent pup and lactating bats, had a higher prevalence of NiV antibodies than juveniles. Antibodies in juveniles 6 months–2 years of age suggested viral circulation within the study period

Looking inside the black box : a theory-based process evaluation alongside a randomised controlled trial of printed educational materials (the Ontario printed educational message, OPEM) to improve referral and prescribing practices in primary care in Ontario, Canada

Background: Randomised controlled trials of implementation strategies tell us whether (or not) an intervention results in changes in professional behaviour but little about the causal mechanisms that produce any change. Theory-based process evaluations collect data on theoretical constructs alongside randomised trials to explore possible causal mechanisms and effect modifiers. This is similar to measuring intermediate endpoints in clinical trials to further understand the biological basis of any observed effects (for example, measuring lipid profiles alongside trials of lipid lowering drugs where the primary endpoint could be reduction in vascular related deaths). This study protocol describes a theory-based process evaluation alongside the Ontario Printed Educational Message (OPEM) trial. We hypothesize that the OPEM interventions are most likely to operate through changes in physicians' behavioural intentions due to improved attitudes or subjective norms with little or no change in perceived behavioural control. We will test this hypothesis using a well-validated social cognition model, the theory of planned behaviour (TPB) that incorporates these constructs. Methods/design: We will develop theory-based surveys using standard methods based upon the TPB for the second and third replications, and survey a subsample of Ontario family physicians from each arm of the trial two months before and six months after the dissemination of the index edition of informed, the evidence based newsletter used for the interventions. In the third replication, our study will converge with the "TRY-ME" protocol (a second study conducted alongside the OPEM trial), in which the content of educational messages was constructed using both standard methods and methods informed by psychological theory. We will modify Dillman's total design method to maximise response rates. Preliminary analyses will initially assess the internal reliability of the measures and use regression to explore the relationships between predictor and dependent variable (intention to advise diabetic patients to have annual retinopathy screening and to prescribe thiazide diuretics for first line treatment of uncomplicated hypertension). We will then compare groups using methods appropriate for comparing independent samples to determine whether there have been changes in the predicted constructs (attitudes, subjective norms, or intentions) across the study groups as hypothesised, and will assess the convergence between the process evaluation results and the main trial results.The OPEM trial and OPEM process evaluation are funded by the Canadian Institute of Health Research (CIHR). The OPEM process evaluation study was developed as part of the CIHR funded interdisciplinary capacity enhancement team KT-ICEBeRG. Gaston Godin, Jeremy Grimshaw and France Légaré hold Canada Research Chairs. Louise Lemyre holds an R.S. McLaughlin Research Chair

Disorder-Induced Critical Phenomena in Hysteresis: Numerical Scaling in Three and Higher Dimensions

We present numerical simulations of avalanches and critical phenomena associated with hysteresis loops, modeled using the zero-temperature random-field Ising model. We study the transition between smooth hysteresis loops and loops with a sharp jump in the magnetization, as the disorder in our model is decreased. In a large region near the critical point, we find scaling and critical phenomena, which are well described by the results of an epsilon expansion about six dimensions. We present the results of simulations in 3, 4, and 5 dimensions, with systems with up to a billion spins (1000^3).Comment: Condensed and updated version of cond-mat/9609072,``Disorder-Induced Critical Phenomena in Hysteresis: A Numerical Scaling Analysis'

Satellite Telemetry and Long-Range Bat Movements

Background: Understanding the long-distance movement of bats has direct relevance to studies of population dynamics, ecology, disease emergence, and conservation. Methodology/Principal Findings: We developed and trialed several collar and platform terminal transmitter (PTT) combinations on both free-living and captive fruit bats (Family Pteropodidae: Genus Pteropus). We examined transmitter weight, size, profile and comfort as key determinants of maximized transmitter activity. We then tested the importance of bat-related variables (species size/weight, roosting habitat and behavior) and environmental variables (day-length, rainfall pattern) in determining optimal collar/PTT configuration. We compared battery- and solar-powered PTT performance in various field situations, and found the latter more successful in maintaining voltage on species that roosted higher in the tree canopy, and at lower density, than those that roost more densely and lower in trees. Finally, we trialed transmitter accuracy, and found that actual distance errors and Argos location class error estimates were in broad agreement. Conclusions/Significance: We conclude that no single collar or transmitter design is optimal for all bat species, and that species size/weight, species ecology and study objectives are key design considerations. Our study provides a strategy for collar and platform choice that will be applicable to a larger number of bat species as transmitter size and weight continue to decrease in the future

Hysteresis, Avalanches, and Disorder Induced Critical Scaling: A Renormalization Group Approach

We study the zero temperature random field Ising model as a model for noise and avalanches in hysteretic systems. Tuning the amount of disorder in the system, we find an ordinary critical point with avalanches on all length scales. Using a mapping to the pure Ising model, we Borel sum the $6-\epsilon$ expansion to $O(\epsilon^5)$ for the correlation length exponent. We sketch a new method for directly calculating avalanche exponents, which we perform to $O(\epsilon)$. Numerical exponents in 3, 4, and 5 dimensions are in good agreement with the analytical predictions.Comment: 134 pages in REVTEX, plus 21 figures. The first two figures can be obtained from the references quoted in their respective figure captions, the remaining 19 figures are supplied separately in uuencoded forma

Identification of Novel Inhibitors of Dietary Lipid Absorption Using Zebrafish

Pharmacological inhibition of dietary lipid absorption induces favorable changes in serum lipoprotein levels in patients that are at risk for cardiovascular disease and is considered an adjuvant or alternative treatment with HMG-CoA reductase inhibitors (statins). Here we demonstrate the feasibility of identifying novel inhibitors of intestinal lipid absorption using the zebrafish system. A pilot screen of an unbiased chemical library identified novel compounds that inhibited processing of fluorescent lipid analogues in live zebrafish larvae. Secondary assays identified those compounds suitable for testing in mammals and provided insight into mechanism of action, which for several compounds could be distinguished from ezetimibe, a drug used to inhibit cholesterol absorption in humans that broadly inhibited lipid absorption in zebrafish larvae. These findings support the utility of zebrafish screening assays to identify novel compounds that target complex physiological processes

Global Change Could Amplify Fire Effects on Soil Greenhouse Gas Emissions

Background: Little is known about the combined impacts of global environmental changes and ecological disturbances on ecosystem functioning, even though such combined impacts might play critical roles in shaping ecosystem processes that can in turn feed back to climate change, such as soil emissions of greenhouse gases.[br/] Methodology/Principal Findings: We took advantage of an accidental, low-severity wildfire that burned part of a long-term global change experiment to investigate the interactive effects of a fire disturbance and increases in CO(2) concentration, precipitation and nitrogen supply on soil nitrous oxide (N(2)O) emissions in a grassland ecosystem. We examined the responses of soil N(2)O emissions, as well as the responses of the two main microbial processes contributing to soil N(2)O production - nitrification and denitrification - and of their main drivers. We show that the fire disturbance greatly increased soil N(2)O emissions over a three-year period, and that elevated CO(2) and enhanced nitrogen supply amplified fire effects on soil N(2)O emissions: emissions increased by a factor of two with fire alone and by a factor of six under the combined influence of fire, elevated CO(2) and nitrogen. We also provide evidence that this response was caused by increased microbial denitrification, resulting from increased soil moisture and soil carbon and nitrogen availability in the burned and fertilized plots. [br/] Conclusions/Significance: Our results indicate that the combined effects of fire and global environmental changes can exceed their effects in isolation, thereby creating unexpected feedbacks to soil greenhouse gas emissions. These findings highlight the need to further explore the impacts of ecological disturbances on ecosystem functioning in the context of global change if we wish to be able to model future soil greenhouse gas emissions with greater confidence

Substrate Type Determines Metagenomic Profiles from Diverse Chemical Habitats

Environmental parameters drive phenotypic and genotypic frequency variations in microbial communities and thus control the extent and structure of microbial diversity. We tested the extent to which microbial community composition changes are controlled by shifting physiochemical properties within a hypersaline lagoon. We sequenced four sediment metagenomes from the Coorong, South Australia from samples which varied in salinity by 99 Practical Salinity Units (PSU), an order of magnitude in ammonia concentration and two orders of magnitude in microbial abundance. Despite the marked divergence in environmental parameters observed between samples, hierarchical clustering of taxonomic and metabolic profiles of these metagenomes showed striking similarity between the samples (>89%). Comparison of these profiles to those derived from a wide variety of publically available datasets demonstrated that the Coorong sediment metagenomes were similar to other sediment, soil, biofilm and microbial mat samples regardless of salinity (>85% similarity). Overall, clustering of solid substrate and water metagenomes into discrete similarity groups based on functional potential indicated that the dichotomy between water and solid matrices is a fundamental determinant of community microbial metabolism that is not masked by salinity, nutrient concentration or microbial abundance

An Open, Large-Scale, Collaborative Effort to Estimate the Reproducibility of Psychological Science

Reproducibility is a defining feature of science. However, because of strong incentives for innovation and weak incentives for confirmation, direct replication is rarely practiced or published. The Reproducibility Project is an open, large-scale, collaborative effort to systematically examine the rate and predictors of reproducibility in psychological science. So far, 72 volunteer researchers from 41 institutions have organized to openly and transparently replicate studies published in three prominent psychological journals in 2008. Multiple methods will be used to evaluate the findings, calculate an empirical rate of replication, and investigate factors that predict reproducibility. Whatever the result, a better understanding of reproducibility will ultimately improve confidence in scientific methodology and findings