A Bioequivalence Test by the Direct Comparison of Concentration-versus-Time Curves Using Local Polynomial Smoothers

In order to test if two chemically or pharmaceutically equivalent products have the same efficacy and/or toxicity, a bioequivalence (BE) study is conducted. The 80%/125% rule is the most commonly used criteria for BE and states that BE cannot be claimed unless the 90% CIs for the ratio of selected pharmacokinetics (PK) parameters of the tested to the reference drug are within 0.8 to 1.25. Considering that estimates of these PK parameters are derived from the concentration-versus-time curves, a direct comparison between these curves motivates an alternative and more flexible approach to test BE. Here, we propose to frame the BE test in terms of an equivalence of concentration-versus-time curves which are constructed using local polynomial smoother (LPS). A metric is presented to quantify the distance between the curves and its 90% CIs are calculated via bootstrapping. Then, we applied the proposed procedures to data from an animal study and found that BE between a generic drug and its brand name cannot be concluded, which was consistent with the results by applying the 80%/125% rule. However, the proposed procedure has the advantage of testing only on a single metric, instead of all PK parameters

Mechanical behaviour of glass fiber weaven UD/high fluidity PA-based polymers for automotive applications

International audienceThis experimental work addresses the mechanical behavior of weaven UD glass fiber-thermoplastic composites designed for layered materials to be used in the automotive industry. The investigation was implemented in terms of the formulation of the PA66-based thermoplastic resins, the architecture of the fibrous reinforcement (warp spacer) and the glass fiber content. Longitudinal and transverse tensile tests results demonstrate the excellent mechanical behavior of these composites, which correlates with the rheological/permeability properties and wettability behaviour. © 2016 Author(s)

Mechanical behaviour of glass fiber weaven UD/high fluidity PA-based polymers for automotive applications

International audienceThis experimental work addresses the mechanical behavior of weaven UD glass fiber-thermoplastic composites designed for layered materials to be used in the automotive industry. The investigation was implemented in terms of the formulation of the PA66-based thermoplastic resins, the architecture of the fibrous reinforcement (warp spacer) and the glass fiber content. Longitudinal and transverse tensile tests results demonstrate the excellent mechanical behavior of these composites, which correlates with the rheological/permeability properties and wettability behaviour. © 2016 Author(s)

RNA Identification of PRIME Cells Predicting Rheumatoid Arthritis Flares

BACKGROUND Rheumatoid arthritis, like many inflammatory diseases, is characterized by episodes of quiescence and exacerbation (flares). The molecular events leading to flares are unknown. METHODS We established a clinical and technical protocol for repeated home collection of blood in patients with rheumatoid arthritis to allow for longitudinal RNA sequencing (RNA-seq). Specimens were obtained from 364 time points during eight flares over a period of 4 years in our index patient, as well as from 235 time points during flares in three additional patients. We identified transcripts that were differentially expressed before flares and compared these with data from synovial single-cell RNA-seq. Flow cytometry and sorted-blood-cell RNA-seq in additional patients were used to validate the findings. RESULTS Consistent changes were observed in blood transcriptional profiles 1 to 2 weeks before a rheumatoid arthritis flare. B-cell activation was followed by expansion of circulating CD45−CD31−PDPN+ preinflammatory mesenchymal, or PRIME, cells in the blood from patients with rheumatoid arthritis; these cells shared features of inflammatory synovial fibroblasts. Levels of circulating PRIME cells decreased during flares in all 4 patients, and flow cytometry and sorted-cell RNA-seq confirmed the presence of PRIME cells in 19 additional patients with rheumatoid arthritis. CONCLUSIONS Longitudinal genomic analysis of rheumatoid arthritis flares revealed PRIME cells in the blood during the period before a flare and suggested a model in which these cells become activated by B cells in the weeks before a flare and subsequently migrate out of the blood into the synovium. (Funded by the National Institutes of Health and others.