Etoricoxib in the treatment of osteoarthritis over 52-weeks: a double-blind, active-comparator controlled trial [NCT00242489]

BACKGROUND: The aim of this study was to evaluate the long-term efficacy and tolerability of etoricoxib, a COX-2 selective inhibitor, in osteoarthritis (OA) patients. METHODS: A double-blind, randomized, multicenter study was conducted in 617 patients with OA of the knee. The base study was 14 weeks in duration and consisted of 2 parts; in Part I (6 weeks), patients were allocated to once daily oral etoricoxib 5, 10, 30, 60, 90 mg or placebo. In Part II (8 weeks); the placebo, etoricoxib 5 and 10 mg groups were reallocated to etoricoxib 30, 60, or 90 mg qd or diclofenac 50 mg t.i.d. Treatment was continued for consecutive 12 and 26 week extensions. Primary efficacy endpoints were the WOMAC VA 3.0 pain subscale and investigator global assessment of disease status. Safety and tolerability were assessed by collecting adverse events throughout the study. RESULTS: Compared with placebo, the etoricoxib groups displayed significant (p < 0.05), dose-dependent efficacy for all primary endpoints in Part I; efficacy was maintained throughout the 52 weeks of the study. During the 46-week active-comparator controlled period, the etoricoxib groups demonstrated clinical efficacy that was similar to that of diclofenac 150 mg and was generally well tolerated, with a lower incidence of gastrointestinal (GI) nuisance symptoms compared with diclofenac (13.1, 14.7, and 13.5% for etoricoxib 30, 60, and 90 mg, respectively compared with 22.5% for diclofenac). CONCLUSION: In this extension study, etoricoxib, at doses ranging from 30 to 90 mg, demonstrated a maintenance of significant clinical efficacy in patients with OA through 52 weeks of treatment. Etoricoxib displayed clinical efficacy similar to diclofenac 150 mg and was generally well tolerated

Identification of key parameters controlling demographically structured vegetation dynamics in a land surface model: CLM4.5(FATES)

Vegetation plays an important role in regulating global carbon cycles and is a key component of the Earth system models (ESMs) that aim to project Earth's future climate. In the last decade, the vegetation component within ESMs has witnessed great progress from simple "big-leaf" approaches to demographically structured approaches, which have a better representation of plant size, canopy structure, and disturbances. These demographically structured vegetation models typically have a large number of input parameters, and sensitivity analysis is needed to quantify the impact of each parameter on the model outputs for a better understanding of model behavior. In this study, we conducted a comprehensive sensitivity analysis to diagnose the Community Land Model coupled to the Functionally Assembled Terrestrial Simulator, or CLM4.5(FATES). Specifically, we quantified the first- and second-order sensitivities of the model parameters to outputs that represent simulated growth and mortality as well as carbon fluxes and stocks for a tropical site with an extent of 1×1°. While the photosynthetic capacity parameter (Vc;max25) is found to be important for simulated carbon stocks and fluxes, we also show the importance of carbon storage and allometry parameters, which determine survival and growth strategies within the model. The parameter sensitivity changes with different sizes of trees and climate conditions. The results of this study highlight the importance of understanding the dynamics of the next generation of demographically enabled vegetation models within ESMs to improve model parameterization and structure for better model fidelity

Electronic Health Literacy Across the Lifespan: Measurement Invariance Study

Background: Electronic health (eHealth) information is ingrained in the healthcare experience to engage patients across the lifespan. Both eHealth accessibility and optimization are influenced by lifespan development, as older adults experience greater challenges accessing and using eHealth tools as compared to their younger counterparts. The eHealth Literacy Scale (eHEALS) is the most popular measure used to assess patient confidence locating, understanding, evaluating, and acting upon online health information. Currently, however, the factor structure of the eHEALS across discrete age groups is not well understood, which limits its usefulness as a measure of eHealth literacy across the lifespan. Objective: The purpose of this study was to examine the structure of eHEALS scores and the degree of measurement invariance among US adults representing the following generations: Millennials (18-35-year-olds), Generation X (36-51-year-olds), Baby Boomers (52-70-year-olds), and the Silent Generation (71-84-year-olds). Methods: Millennials (N=281, mean 26.64 years, SD 5.14), Generation X (N=164, mean 42.97 years, SD 5.01), and Baby Boomers/Silent Generation (N=384, mean 62.80 years, SD 6.66) members completed the eHEALS. The 3-factor (root mean square error of approximation, RMSEA=.06, comparative fit index, CFI=.99, Tucker-Lewis index, TLI=.98) and 4-factor (RMSEA=.06, CFI=.99, TLI=.98) models showed the best global fit, as compared to the 1- and 2-factor models. However, the 4-factor model did not have statistically significant factor loadings on the 4th factor, which led to the acceptance of the 3-factor eHEALS model. The 3-factor model included eHealth Information Awareness, Search, and Engagement. Pattern invariance for this 3-factor structure was supported with acceptable model fit (RMSEA=.07, Δχ2=P>.05, ΔCFI=0). Compared to Millennials and members of Generation X, those in the Baby Boomer and Silent Generations reported less confidence in their awareness of eHealth resources (P<.001), information seeking skills (P=.003), and ability to evaluate and act on health information found on the Internet (P<.001). Results: Young (18-48-year olds, N=411) and old (49-84-year olds, N=419) adults completed the survey. A 3-factor model had the best fit (RMSEA=.06, CFI=.99, TLI=.98), as compared to the 1-factor, 2-factor, and 4-factor models. These 3-factors included eHealth Information Awareness (2 items), Information Seeking (2 items), and Information and Evaluation (4 items). Pattern invariance was supported with the acceptable model fit (RMSEA=.06, Δχ2=P>.05, ΔCFI=0). Compared with younger adults, older adults had less confidence in eHealth resource awareness (P<.001), information seeking skills (P<.01), and ability to evaluate and act upon online health information (P<.001). Conclusions: The eHEALS can be used to assess, monitor uniquely, and evaluate Internet users’ awareness of eHealth resources, information seeking skills, and engagement abilities. Configural and pattern invariance was observed across all generation groups in the 3-factor eHEALS model. To meet gold the standards for factor interpretation (ie, 3 items or indicators per factor), future research is needed to create and assess additional eHEALS items. Future research is also necessary to identify and test items for a fourth factor, one that captures the social nature of eHealth

The fate of the homoctenids (Tentaculitoidea) during the Frasnian-Famennian mass extinction (Late Devonian)

The homoctenids (Tentaculitoidea) are small, conical-shelled marine animals which are amongst the most abundant and widespread of all Late Devonian fossils. They were a principal casualty of the Frasnian-Famennian (F-F, Late Devonian) mass extinction, and thus provide an insight into the extinction dynamics. Despite their abundance during the Late Devonian, they have been largely neglected by extinction studies. A number of Frasnian-Famennian boundary sections have been studied, in Poland, Germany, France, and the United States. These sections have yielded homoctenids, which allow precise recognition of the timing of the mass extinction. It is clear that the homoctenids almost disappear from the fossil record during the latest Frasnian “Upper Kellwasser Event”. The coincident extinction of this pelagic group, and the widespread development of intense marine anoxia within the water column, provides a causal link between anoxia and the F-F extinction. Most notable is the sudden demise of a group, which had been present in rock-forming densities, during this anoxic event. One new species, belonging to Homoctenus is described, but is not formally named here

The impact of bisphosphonates on the osteoblast proliferation and Collagen gene expression in vitro

<p>Abstract</p> <p>Background</p> <p>Bisphosphonates are widely used in the clinical treatment of bone diseases with increased bone resorption. In terms of side effects, they are known to be associated with osteonecrosis of the jaw (BONJ).</p> <p>The objective of this study was to evaluate the effect of bisphosphonates on osteoblast proliferation by cell count and gene expression analysis of cyclin D1 <it>in vitro</it>. Furthermore, the gene expression of the extracellular matrix protein collagen type I was evaluated. Nitrogen-containing and non-nitrogen-containing bisphosphonates have been compared on gene expression levels.</p> <p>Methods</p> <p>Human osteoblast obtained from hip bone were stimulated with zoledronate, ibandronate and clodronate at concentrations of 5 × 10^-5M over the experimental periods of 1, 2, 5, 10 and 14 days. At each point in time, the cells were dissolved, the mRNA extracted, and the gene expression level of cyclin D1 and collagen type I were quantified by Real-Time RT-PCR. The gene expression was compared to an unstimulated osteoblast cell culture for control.</p> <p>Results</p> <p>The proliferation appeared to have been influenced only to a small degree by bisphosphonates. Zolendronate led to a lower cyclin D1 gene expression after 10 days. The collagen gene expression was enhanced by nitrogen containing bisphosphonates, decreased however after day 10. The non-nitrogen-containing bisphosphonate clodronate, however, did not significantly influence cyclin D1 and collagen gene expression.</p> <p>Conclusions</p> <p>The above data suggest a limited influence of bisphosphonates on osteoblast proliferation, except for zoledronate. The extracellular matrix production seems to be initially advanced and inhibited after 10 days. Interestingly, clodronate has little influence on osteoblast proliferation and extracellular matrix production in terms of cyclin D1 and collagen gene expression.</p

In vitro metabolism of beclomethasone dipropionate, budesonide, ciclesonide, and fluticasone propionate in human lung precision-cut tissue slices

<p>Abstract</p> <p>Background</p> <p>The therapeutic effect of inhaled corticosteroids (ICS) may be affected by the metabolism of the drug in the target organ. We investigated the <it>in vitro </it>metabolism of beclomethasone dipropionate (BDP), budesonide (BUD), ciclesonide (CIC), and fluticasone propionate (FP) in human lung precision-cut tissue slices. CIC, a new generation ICS, is hydrolyzed by esterases in the upper and lower airways to its pharmacologically active metabolite desisobutyryl-ciclesonide (des-CIC).</p> <p>Methods</p> <p>Lung tissue slices were incubated with BDP, BUD, CIC, and FP (initial target concentration of 25 μM) for 2, 6, and 24 h. Cellular viability was assessed using adenosine 5'-triphosphate content and protein synthesis in lung slices. Metabolites and remaining parent compounds in the tissue samples were analyzed by HPLC with UV detection.</p> <p>Results</p> <p>BDP was hydrolyzed to the pharmacologically active metabolite beclomethasone-17-monopropionate (BMP) and, predominantly, to inactive beclomethasone (BOH). CIC was hydrolyzed initially to des-CIC with a slower rate compared to BDP. A distinctly smaller amount (approximately 10-fold less) of fatty acid esters were formed by BMP (and/or BOH) than by BUD or des-CIC. The highest relative amounts of fatty acid esters were detected for BUD. For FP, no metabolites were detected at any time point. The amount of drug-related material in lung tissue (based on initial concentrations) at 24 h was highest for CIC, followed by BUD and FP; the smallest amount was detected for BDP.</p> <p>Conclusion</p> <p>The <it>in vitro </it>metabolic pathways of the tested ICS in human lung tissue were differing. While FP was metabolically stable, the majority of BDP was converted to inactive polar metabolites. The formation of fatty acid conjugates was confirmed for BMP (and/or BOH), BUD, and des-CIC.</p

The mathematical review system: does reviewer status play a role in the citation process?

This paper revisits an aspect of citation theory (i.e., citer motivation) with respect to the Mathematical Review system and the reviewer’s role in mathematics. We focus on a set of journal articles (369) published in Singularity Theory (1974–2003), the mathematicians who wrote editorial reviews for these articles, and the number of citations each reviewed article received within a 5 year period. Our research hypothesis is that the cognitive authority of a high status reviewer plays a positive role in how well a new article is received and cited by others. Bibliometric evidence points to the contrary: Singularity Theorists of lower status (junior researchers) have reviewed slightly more well-cited articles (2–5 citations, excluding author self-citations) than their higher status counterparts (senior researchers). One explanation for this result is that lower status researchers may have been asked to review ‘trendy’ or more accessible parts of mathematics, which are easier to use and cite. We offer further explanations and discuss a number of implications for a theory of citation in mathematics. This research opens the door for comparisons to other editorial review systems, such as book reviews written in the social sciences or humanities

Ears of the Armadillo: Global Health Research and Neglected Diseases in Texas

Neglected tropical diseases (NTDs) have\ud been recently identified as significant public\ud health problems in Texas and elsewhere in\ud the American South. A one-day forum on the\ud landscape of research and development and\ud the hidden burden of NTDs in Texas\ud explored the next steps to coordinate advocacy,\ud public health, and research into a\ud cogent health policy framework for the\ud American NTDs. It also highlighted how\ud U.S.-funded global health research can serve\ud to combat these health disparities in the\ud United States, in addition to benefiting\ud communities abroad