83 research outputs found

    Rheumatoid arthritis treated with 6-months of first-line biologic or biosimilar therapy: an updated systematic review and network meta-analysis.

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    OBJECTIVES: The aim of this study was to estimate the effectiveness of first-line biologic disease modifying drugs(boDMARDs), and their approved biosimilars (bsDMARDs), compared with conventional (csDMARD) treatment, in terms of ACR (American College of Rheumatology) and EULAR (European League against Rheumatism) responses. METHODS: Systematic literature search, on eight databases to January 2017, sought ACR and EULAR data from randomized controlled trials (RCTs) of boDMARDs / bsDMARDs (in combination with csDMARDs, or monotherapy). Two adult populations: methotrexate (MTX)-naïve patients with severe active RA; and csDMARD-experienced patients with moderate-to-severe active RA. Network meta-analyses (NMA) were conducted using a Bayesian Markov chain Monte Carlo simulation using a random effects model with a probit link function for ordered categorical. RESULTS: Forty-six RCTs met the eligibility criteria. In the MTX-naïve severe active RA population, no biosimilar trials meeting the inclusion criteria were identified. MTX plus methylprednisolone (MP) was most likely to achieve the best ACR response. There was insufficient evidence that combination boDMARDs was superior to intensive (two or more) csDMARDs. In the csDMARD-experienced, moderate-to-severe RA population, the greatest effects for ACR responses were associated with tocilizumab (TCZ) monotherapy, and combination therapy (plus MTX) with bsDMARD etanercept (ETN) SB4, boDMARD ETN and TCZ. These treatments also had the greatest effects on EULAR responses. No clear differences were found between the boDMARDs and their bsDMARDs. CONCLUSIONS: In MTX-naïve patients, there was insufficient evidence that combination boDMARDs was superior to two or more csDMARDs. In csDMARD-experienced patients, boDMARDs and bsDMARDs were comparable and all combination boDMARDs / bsDMARDs were superior to single csDMARD

    Oligomeric Status and Nucleotide Binding Properties of the Plastid ATP/ADP Transporter 1: Toward a Molecular Understanding of the Transport Mechanism

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    Background: Chloroplast ATP/ADP transporters are essential to energy homeostasis in plant cells. However, their molecular mechanism remains poorly understood, primarily due to the difficulty of producing and purifying functional recombinant forms of these transporters. Methodology/Principal Findings: In this work, we describe an expression and purification protocol providing good yields and efficient solubilization of NTT1 protein from Arabidopsis thaliana. By biochemical and biophysical analyses, we identified the best detergent for solubilization and purification of functional proteins, LAPAO. Purified NTT1 was found to accumulate as two independent pools of well folded, stable monomers and dimers. ATP and ADP binding properties were determined, and Pi, a co-substrate of ADP, was confirmed to be essential for nucleotide steady-state transport. Nucleotide binding studies and analysis of NTT1 mutants lead us to suggest the existence of two distinct and probably inter-dependent binding sites. Finally, fusion and deletion experiments demonstrated that the C-terminus of NTT1 is not essential for multimerization, but probably plays a regulatory role, controlling the nucleotide exchange rate. Conclusions/Significance: Taken together, these data provide a comprehensive molecular characterization of a chloroplas

    Clinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spectrometry: a worldwide collaborative project.

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    Urban use of VHR images on Bukavu (Democratic Republic of Congo)

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    peer reviewedThe main purpose of this study was to show potential uses of very high resolution (VHR) image in an urban analysis of Bukavu in the Democratic Republic of Congo. As for many of the Third-World cities, Bukavu grew up during the last decades and available topographical information on Bukavu dates back to the middle of the twentieth century. This lack of updated information can be compensated by an appropriate use of VHR images. In this study, IKONOS image recorded on the 14th February 2001 was used. Image registration are highly dependant on accurate Digital Elevation Models (DEM), these last ones are also useful in urban analyses. The range between the minimum and maximum altitudes observed in the image was more than 500 meters. Furthermore, the viewing inclination angle is more than 28 degrees. In this case, orthorectification is mandatory for correcting relief displacements. Nevertheless, the lack of good Ground Control Points (GPS’s) on the old topographic maps and the failure to collect field verification data in Bukavu explains the remaining global 2D RMSE of 10 meters. For easier image interpretation, multispectral (4m) and panchromatic (1m) images were fused together by means of the LMVM algorithm. Depending on the object, the Computer Aided Photo Interpretation (CAPI) uses or does not use the near infrared information (true or false colour composite). For a more detailed interpretation about the city morphology we draped the 1m multispectral fused image over the 1m resolution DEM grid. The Built-up Area Index (BAI) computed on the urban mask obtained by CAPI and classification of the vegetation, was compared with the 1954 situation interpreted from topographic maps. The present city shows higher BAI values and in the same time the centre of the city has clearly shifted southward. Statistical analyses are also done on built-up versus slope data. The lack of good GCP’s and the use of DEM produced inaccurate orthorectification which was not adequate for topographical features extraction. Nevertheless the present extensions of Bukavu built-up areas are more than the double of those observed at the beginning of the last half century. New constructions are located on steeper slopes where landslides are frequents. More features could be extracted from the Ikonos image if good GPS measurements were made and if verification by the city authorities was possible. Some practical applications of this study could involve determining better location of new Bukavu extensions
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