33 research outputs found
Reaction-diffusion equations with spatially distributed hysteresis
The paper deals with reaction-diffusion equations involving a hysteretic
discontinuity in the source term, which is defined at each spatial point. In
particular, such problems describe chemical reactions and biological processes
in which diffusive and nondiffusive substances interact according to hysteresis
law. We find sufficient conditions that guarantee the existence and uniqueness
of solutions as well as their continuous dependence on initial data.Comment: 30 pages, 14 figure
ELECTRONIC STRUCTURE OF FeSi
The full set of high-energy spectroscopy measurements including X-ray
photoelectron valence band spectra and soft X-ray emission valence band spectra
of both components of FeSi (Fe K_beta_5, Fe L_alpha, Si K_beta_1,3 and Si
L_2,3) are performed and compared with the results of ab-initio band structure
calculations using the linearized muffin-tin orbital method and linearized
augmented plane wave method.Comment: 11 pages + 3 PostScript figures, RevTex3.0, to be published in
J.Phys.:Cond.Matte
Subjective and Objective Measures of Dryness Symptoms in Primary Sjögren's Syndrome::Capturing the Discrepancy
Objective: To develop a novel method for capturing the discrepancy between objective tests and subjective dryness symptoms (a sensitivity scale) and to explore predictors of dryness sensitivity. Methods: Archive data from the UK Primary Sjögren's Syndrome Registry (n = 688) were used. Patients were classified on a scale from −5 (stoical) to +5 (sensitive) depending on the degree of discrepancy between their objective and subjective symptoms classes. Sensitivity scores were correlated with demographic variables, disease-related factors, and symptoms of pain, fatigue, anxiety, and depression. Results: Patients were on average relatively stoical for both types of dryness symptoms (mean ± SD ocular dryness −0.42 ± 2.2 and −1.24 ± 1.6 oral dryness). Twenty-seven percent of patients were classified as sensitive to ocular dryness and 9% to oral dryness. Hierarchical regression analyses identified the strongest predictor of ocular dryness sensitivity to be self-reported pain and that of oral dryness sensitivity to be self-reported fatigue. Conclusion: Ocular and oral dryness sensitivity can be classified on a continuous scale. The 2 symptom types are predicted by different variables. A large number of factors remain to be explored that may impact symptom sensitivity in primary Sjögrenʼs syndrome, and the proposed method could be used to identify relatively sensitive and stoical patients for future studies.</p
Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials
Background
Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response.
Methods
We did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab.
Findings
In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo.
Interpretation
Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases.
Funding
UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology