Low-Density Granulocytes Are a Novel Immunopathological Feature in Both Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

Objective: To investigate whether low-density granulocytes (LDGs) are an immunophenotypic feature of patients with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD). Methods: Blood samples were collected from 20 patients with NMOSD and 17 patients with MS, as well as from 15 patients with Systemic Lupus Erythematosus (SLE) and 23 Healthy Donors (HD). We isolated peripheral blood mononuclear cells (PBMCs) with density gradient separation and stained the cells with antibodies against CD14, CD15, CD16, and CD45, and analyzed the cells by flow cytometry or imaging flow cytometry. We defined LDGs as CD14-CD15(high) and calculated their share in total PBMC leukocytes (CD45+) as well as the share of CD16(hi) LDGs. Clinical data on disease course, medication, and antibody status were obtained. Results: LDGs were significantly more common in MS and NMOSD than in HDs, comparable to SLE samples (median values HD 0.2%, MS 0.9%, NMOSD 2.1%, SLE 4.3%). 0/23 of the HDs, but 17/20 NMOSD and 11/17 MS samples as well as 13/15 SLE samples had at least 0.7 % LDGs. NMOSD patients without continuous immunosuppressive treatment had significantly more LDGs compared to their treated counterparts. LDG nuclear morphology ranged from segmented to rounded, suggesting a heterogeneity within the group. Conclusion: LDGs are a feature of the immunophenotype in some patients with MS and NMOSD

The translation, validity and reliability of the German version of the Fremantle Back Awareness Questionnaire

Background: The Fremantle Back Awareness Questionnaire (FreBAQ) claims to assess disrupted self-perception of the back. The aim of this study was to develop a German version of the Fre-BAQ (FreBAQ-G) and assess its test-retest reliability, its known-groups validity and its convergent validity with another purported measure of back perception. Methods: The FreBaQ-G was translated following international guidelines for the transcultural adaptation of questionnaires. Thirty-five patients with non-specific CLBP and 48 healthy participants were recruited. Assessor one administered the FreBAQ-G to each patient with CLBP on two separate days to quantify intra-observer reliability. Assessor two administered the FreBaQ-G to each patient on day 1. The scores were compared to those obtained by assessor one on day 1 to assess inter-observer reliability. Known-groups validity was quantified by comparing the FreBAQ-G score between patients and healthy controls. To assess convergent validity, patient\u27s FreBAQ-G scores were correlated to their two-point discrimination (TPD) scores. Results: Intra- and Inter-observer reliability were both moderate with ICC3.1 = 0.88 (95%CI: 0.77 to 0.94) and 0.89 (95%CI: 0.79 to 0.94), respectively. Intra- and inter-observer limits of agreement (LoA) were 6.2 (95%CI: 5.0±8.1) and 6.0 (4.8±7.8), respectively. The adjusted mean difference between patients and controls was 5.4 (95%CI: 3.0 to 7.8, p\u3c0.01). Patient\u27s FreBAQ-G scores were not associated with TPD thresholds (Pearson\u27s r = -0.05, p = 0.79). Conclusions: The FreBAQ-G demonstrated a degree of reliability and known-groups validity. Interpretation of patient level data should be performed with caution because the LoA were substantial. It did not demonstrate convergent validity against TPD. Floor effects of some items of the FreBAQ-G may have influenced the validity and reliability results. The clinimetric properties of the FreBAQ-G require further investigation as a simple measure of disrupted self-perception of the back before firm recommendations on its use can be made

Unorthodoxy in legislation: The Hungarian experience

This paper deals with legal unorthodoxy. The main idea is to study the so-called unorthodox taxes Hungary has adopted in recent years. The study of unorthodox taxes will be preceded by a more general discussion of how law is made under unorthodoxy, and what are the special features of unorthodox legal policy. Unorthodoxy challenges equality before the law and is critical towards mass democracies. It also raises doubts on the operability of the rule of law, relying on personal skills, or loyalty, rather than on impersonal mechanisms arising from checks and balances as developed by the division of political power. Besides, for lack of legal suppositions, legislation suffers from casuistry and regulatory capture

Seismically induced landslide hazard and exposure modelling in Southern California based on the 1994 Northridge, California earthquake event

Quantitative modelling of landslide hazard, as opposed to landslide susceptibility, as a function of the earthquake trigger is vital in understanding and assessing future potential exposure to landsliding. Logistic regression analysis is a method commonly used to assess susceptibility to landsliding; however, estimating probability of landslide hazard as a result of an earthquake trigger is rarely undertaken. This paper utilises a very detailed landslide inventory map and a comprehensive dataset on peak ground acceleration for the 1994 Mw6.7 Northridge earthquake event to fit a landslide hazard logistic regression model. The model demonstrates a high success rate for estimating probability of landslides as a result of earthquake shaking. Seven earthquake magnitude scenarios were simulated using the Open Source Seismic Hazard Analysis (OpenSHA) application to simulate peak ground acceleration, a covariate of landsliding, for each event. The exposure of assets such as population, housing and roads to high levels of shaking and high probabilities of landsliding was estimated for each scenario. There has been urban development in the Northridge region since 1994, leading to an increase in prospective exposure of assets to the earthquake and landslide hazards in the event of a potential future earthquake. As the earthquake scenario magnitude increases, the impact from earthquake shaking initially increases then quickly levels out, but potential losses from landslides increase at a rapid rate. The modelling approach, as well as the specific model, developed in this paper can be used to estimate landslide probabilities as a result of an earthquake event for any scenario where the peak ground acceleration variable is available