Relationship between time-integrated disease activity estimated by DAS28-CRP and radiographic progression of anatomical damage in patients with early rheumatoid arthritis

<p>Abstract</p> <p>Background</p> <p>The main aim of the study was to investigate the relationship between persistent disease activity and radiographic progression of joint damage in early rheumatoid arthritis (ERA).</p> <p>Methods</p> <p>Forty-eight patients with active ERA was assessed every 3 months for disease activity for 3 years. Radiographic damage was measured by the Sharp/van der Heijde method (SHS). The cumulative inflammatory burden was estimated by the time-integrated values (area under the curve-AUC) of Disease Activity Score 28 joint based on C-reactive protein (DAS28-CRP) in rapid progressors versus non-progressors. Bland and Altman's 95% limits of agreement method were used to estimate the smallest detectable difference (SDD) of radiographic progression. The relationship between clinical and laboratory predictors of radiographic progression and their interactions with time was analysed by logistic regression model.</p> <p>Results</p> <p>After 3-years of follow-up, radiographic progression was observed in 54.2% (95%CI: 39.8% to 67.5%) of patients and SDD was 9.5 for total SHS. The percentage of patients with erosive disease increased from 33.3% at baseline to 76% at 36 months. The total SHS of the progressors worsened from a median (interquartile range) of 18.5 (15-20) at baseline to 38.5 (34-42) after 3 years (p < 0.0001) whereas non-progressors worsened from a median of 14.5 (13-20) at baseline to 22.5 (20-30) after 3 years (p < 0.001). In the regression model, time-integrated values of DAS28-CRP and anti-CCP positivity have the highest positive predictive value for progression (both at level of p < 0.0001). Radiographic progression was also predicted by a positive IgM-RF (p0.0009), and a high baseline joint damage (p = 0.0044).</p> <p>Conclusions</p> <p>These data indicate that the level of disease activity, as measured by time-integrated DAS28-CRP, anti-CCP and IgM-RF positivity and a high baseline joint damage, affects subsequent progression of radiographic damage in ERA.</p

Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles

Release of membrane vesicles, a process conserved in both prokaryotes and eukaryotes, represents an evolutionary link, and suggests essential functions of a dynamic extracellular vesicular compartment (including exosomes, microparticles or microvesicles and apoptotic bodies). Compelling evidence supports the significance of this compartment in a broad range of physiological and pathological processes. However, classification of membrane vesicles, protocols of their isolation and detection, molecular details of vesicular release, clearance and biological functions are still under intense investigation. Here, we give a comprehensive overview of extracellular vesicles. After discussing the technical pitfalls and potential artifacts of the rapidly emerging field, we compare results from meta-analyses of published proteomic studies on membrane vesicles. We also summarize clinical implications of membrane vesicles. Lessons from this compartment challenge current paradigms concerning the mechanisms of intercellular communication and immune regulation. Furthermore, its clinical implementation may open new perspectives in translational medicine both in diagnostics and therapy

A framework for the detection of de novo mutations in family-based sequencing data

Germline mutation detection from human DNA sequence data is challenging due to the rarity of such events relative to the intrinsic error rates of sequencing technologies and the uneven coverage across the genome. We developed PhaseByTransmission (PBT) to identify de novo single nucleotide variants and short insertions and deletions (indels) from sequence data collected in parent-offspring trios. We compute the joint probability of the data given the genotype likelihoods in the individual family members, the known familial relationships and a prior probability for the mutation rate. Candidate de novo mutations (DNMs) are reported along with their posterior probability, providing a systematic way to prioritize them for validation. Our tool is integrated in the Genome Analysis Toolkit and can be used together with the ReadBackedPhasing module to infer the parental origin of DNMs based on phase-informative reads. Using simulated data, we show that PBT outperforms existing tools, especially in low coverage data and on the X chromosome. We further show that PBT displays high validation rates on empirical parent-offspring sequencing data for whole-exome data from 104 trios and X-chromosome data from 249 parent-offspring families. Finally, we demonstrate an association between father's age at conception and the number of DNMs in female offspring's X chromosome, consistent with previous literature reports

Effect of cover management factor in quantification of soil loss: case study of Sungai Akah subwatershed, Baram River basin Sarawak, Malaysia

© 2017 Informa UK Limited, trading as Taylor & Francis Group The present study evaluates the effectiveness and suitability of cover management factors (C factor) generated through different techniques like land use/land cover-based arbitrary value (C LULC ), Normalised Different Vegetation Index-based methods C NDVI1 and C NDVI2 and Modified Soil Adjusted Vegetation Index 2-based method (C MSAVI2 ). The C factors generated using these four methods were tested in the calculation and assessment of annual average soil loss from an upland forested subwatershed in the Baram river basin using the Revised Universal Soil Loss Equation (RUSLE). The four cover management factor maps generated by this analysis show some variation among the results. The LULC method uses a single arbitrary value for each LULC type mapped in the subwatershed. The other three methods show a range of C values within each mapped LULC type. The effects of these variations were tested in the RUSLE by keeping the factors such as rainfall erosivity (R), soil erodibility (K), slope-length and steepness (LS) constant. The maximum annual average soil loss is 1191 t. ha -1 . y -1 based on the C LULC . Soil losses estimated with other three methods are very different compared to those estimated with the C LULC method. The highest calculated soil loss values were 1832, 1674 and 1608 t. ha -1 . y -1 in the study area based, respectively, on C NDVI1 , C NDVI2 and C MSAVI2 C factors. These maximum values represent the worst pixel scenario values of soil loss in the region. The statistical analysis performed indicates different relationship between the parameters and suggests the acceptance of the methodology based on C NDVI2 for the study area, instead of a single value method such as C LULC . Among the other two methods, the C MSAVI2 was found to be more consistent than the C NDVI1 method, but both methods lead to over-prediction of annual soil loss rate and therefore need to be reconsidered before applied in the RUSLE

Soil loss, productivity and cropland values GIS-based analysis and trends in the Basilicata region (Southern Italy) from 1980 to 2013

This paper concerns the trends assessment of the productivity values and croplands values of specific crops (cereals (arable cereals land), vineyards, olive-growing lands) in the Basilicata region at regional scale, from 1980 to 2013, in relation to the soil loss evaluated through the USPED method. The comparative analysis shows the interrelations between the soil loss by erosion and the economic value deriving from the erosive phenomenon affecting the croplands considered