65 research outputs found
Body mass index and treatment survival in patients with RA starting treatment with TNF alpha-inhibitors: long-term follow-up in the real-life METEOR registry
Objectives To study whether there is an association between body mass index (BMI) category and survival of various tumour necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA) patients in a real-life longitudinal international registry.Methods Data from 5230 patients with RA starting treatment with any TNFi were selected from the METEOR registry. Patients were divided into six BMI categories: 3.7% underweight, BMI40 kg/m(2). Time on treatment in the different BMI categories was compared for all TNFi combined and for the infliximab, adalimumab and etanercept separately, using Kaplan-Meier curves and Cox regression analyses. Cox regression analyses were adjusted for potential confounders, with follow-up censored at 5000 days.Results Patients in obesity class II (HR 1.28, 95% CI 1.06 to 1.54) and III (HR 1.67, 95% CI 1.29 to 2.18) and underweight patients (HR 1.30, 95% CI 1.07 to 1.58) showed statistically significantly shorter TNFi survival than normal weight patients. The effect in underweight patients was strongest for infliximab (HR 1.82, 95% CI 1.20 to 2.76), the effect in overweight patients was strongest for infliximab (category II (HR 1.49, 95% CI 0.98 to 2.26); category III (HR 1.46, 95% CI 0.79 to 2.71)) and etanercept (category II (HR 1.27 95% CI 0.98 to 1.65); category III (HR 1.79, 95% CI 1.25 to 2.55)). No significant effect modification from reported pain was found.Conclusion Both underweight and overweight patients discontinued TNFi treatment earlier than normal weight patients, without evidence of reported pain as the main determinant. It remains uncertain what determines TNFi survival in individual patients.Pathophysiology and treatment of rheumatic disease
Identification and Functional Characterization of G6PC2 Coding Variants Influencing Glycemic Traits Define an Effector Transcript at the G6PC2-ABCB11 Locus
Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P<5×10-7) evidence for two loci not previously highlighted by common variant GWAS: GLP1R (p.Ala316Thr, minor allele frequency (MAF)=1.5%) influencing FG levels, and URB2 (p.Glu594Val, MAF = 0.1%) influencing FI levels. Coding variant associations can highlight potential effector genes at (non-coding) GWAS signals. At the G6PC2/ABCB11 locus, we identified multiple coding variants in G6PC2 (p.Val219Leu, p.His177Tyr, and p.Tyr207Ser) influencing FG levels, conditionally independent of each other and the non-coding GWAS signal. In vitro assays demonstrate that these associated coding alleles result in reduced protein abundance via proteasomal degradation, establishing G6PC2 as an effector gene at this locus. Reconciliation of single-variant associations and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D), the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent association with T2D risk. Coding variant associations for glycemic traits in GWAS signals highlight PCSK1, RREB1, and ZHX3 as likely effector transcripts. These coding variant association signals do not have a major impact on the trait variance explained, but they do provide valuable biological insights
A European Multi Lake Survey dataset of environmental variables, phytoplankton pigments and cyanotoxins
Briófitas do Parque Estadual da Serra do Mar, Núcleo de Santa Virgínia, Estado de São Paulo, Brasil
The criminal justice voluntary sector: concepts and an agenda for an emerging field
This is the peer reviewed version of the following article: Tomczak, P. & Buck, G. (2019). The criminal justice voluntary sector: concepts and an agenda for an emerging field. Howard Journal of Crime and Justice, 58(3), which has been published in final form at https://doi.org/10.1111/hojo.12326. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.Volunteers and voluntary organisations play significant roles pervading criminal justice. They are key actors, with unrecognised potential to shore up criminal justice and/or collaboratively reshape social justice. Unlike public and for-profit agents, criminal justice volunteers and voluntary organisations (CJVVOs) have been neglected by scholars. We call for analyses of diverse CJVVOs, in national and comparative contexts. We provide three categories to highlight distinctive organising auspices, which hold across criminal justice: statutory volunteers, quasi-statutory volunteers and voluntary organisations. The unknown implications of these different forms of non-state, non-profit justice involvement deserve far greater attention from academics, policymakers and practitioners
Aspectos brioflorísticos e fitogeográficos de duas formações costeiras de Floresta Atlântica da Serra do Mar, Ubatuba/SP, Brasil
Proceedings of the 2016 Childhood Arthritis and Rheumatology Research Alliance (CARRA) Scientific Meeting
Stratification strength and light climate explain variation in chlorophyll a at the continental scale in a European multilake survey in a heatwave summer
To determine the drivers of phytoplankton biomass, we collected standardized morphometric, physical, and biological data in 230 lakes across the Mediterranean, Continental, and Boreal climatic zones of the European continent. Multilinear regression models tested on this snapshot of mostly eutrophic lakes (median total phosphorus [TP] = 0.06 and total nitrogen [TN] = 0.7 mg L−1), and its subsets (2 depth types and 3 climatic zones), show that light climate and stratification strength were the most significant explanatory variables for chlorophyll a (Chl a) variance. TN was a significant predictor for phytoplankton biomass for shallow and continental lakes, while TP never appeared as an explanatory variable, suggesting that under high TP, light, which partially controls stratification strength, becomes limiting for phytoplankton development. Mediterranean lakes were the warmest yet most weakly stratified and had significantly less Chl a than Boreal lakes, where the temperature anomaly from the long-term average, during a summer heatwave was the highest (+4°C) and showed a significant, exponential relationship with stratification strength. This European survey represents a summer snapshot of phytoplankton biomass and its drivers, and lends support that light and stratification metrics, which are both affected by climate change, are better predictors for phytoplankton biomass in nutrient-rich lakes than nutrient concentrations and surface temperature
Computational modeling of stem and progenitor cell kinetics identifies plausible hematopoietic lineage hierarchies.
Classically, hematopoietic stem cell (HSC) differentiation is assumed to
occur via progenitor compartments of decreasing plasticity and
increasing maturity in a specific, hierarchical manner. The classical
hierarchy has been challenged in the past by alternative differentiation
pathways. We abstracted experimental evidence into 10 differentiation
hierarchies, each comprising 7 cell type compartments. By fitting
ordinary differential equation models with realistic waiting time
distributions to time-resolved data of differentiating HSCs from 10
healthy human donors, we identified plausible lineage hierarchies and
rejected others. We found that, for most donors, the classical model of
hematopoiesis is preferred. Surprisingly, multipotent lymphoid
progenitor differentiation into granulocyte-monocyte progenitors is
plausible in 90% of samples. An in silico analysis confirmed
that, even for strong noise, the classical model can be identified
robustly. Our computational approach infers differentiation hierarchies
in a personalized fashion and can be used to gain insights into kinetic
alterations of diseased hematopoiesis
Determination of U-oxidation states in the brannerite structure by electron energy-loss (EELS), x-ray photoelectron (XPS) and diffuse reflectance (DRS) spectroscopies.
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