Improved MSTID modelling and impact on precise GNSS processing

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Direct MSTID mitigation in precise GPS processing

This is the peer reviewed version of the following article: Hernandez, M., Wielgosz, P., Paziewski, J., Krypiak-Gregorczyk, A., Krukowska, M., Stepniak, K., Kaplon, J., Hadas, T., Sosnica, K., Bosy, J., Orús, R., Monte, E., Yang, H., Garcia-Rigo, A., Olivares-Pulido, G. Direct MSTID mitigation in precise GPS processing. "Radio science", Març 2017, vol. 52, núm. 3, p. 321-337, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/2016RS006159/abstract. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-ArchivingIn this paper, the authors summarize a simple and efficient approach developed to mitigate the problem in precise GNSS positioning originated by the most frequent ionospheric wave signatures: the Medium Scale Travelling Ionospheric Disturbances (MSTIDs). The direct GNSS Ionospheric Interferometry technique (hereinafter dGII), presented in this paper, is applied for correcting MSTID effects on precise Real Time Kinematic (RTK) and tropospheric determination. It consists of the evolution of the former climatic Differential Delay Mitigation Model for MSTIDs (DMTID), for real-time conditions, using ionospheric data from a single permanent receiver only. The performance is demonstrated with networks of GNSS receivers in Poland, treated as users under real-time conditions, during two representative days in winter and summer seasons (days 353 and 168 of year 2013). In range domain, dGII typically reduces the ionospheric delay error up to 10-90% of the value when the MSTID mitigation model is not applied. The main dGII impact on precise positioning is that we can obtain reliable RTK position faster. In particular the ASR (ambiguity success rate) parameter increases, from 74% to 83%, with respect to the original uncorrected observations. The average of time to first fix is shortened from 30s to 13s. The improvement in troposphere estimaton, due to any potential impact of the MSTID mitigation model, was most difficult to demonstrate.Peer ReviewedPostprint (author's final draft

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Percentage of Myeloid Dendritic Cells in Peripheral Venous Blood Is Negatively Related to Incidence of Graves’ Orbitopathy

The aim of the study was to evaluate the distribution of blood dendritic cells (DCs) in patients with Graves’ orbitopathy (GO) and to assess the influence of methylprednisolone therapy on subsets of peripheral blood mononuclear cells (PBMCs). Peripheral blood DC subsets were analyzed by flow cytometry in patients with active GO (n=17), inactive GO (n=8), and Graves’ disease (GD) without GO (n=8) and controls (n=15); additionally, in patients with active GO (n=17), analyses were done at three time points, i.e., before methylprednisolone treatment and after 6 weeks and after 12 weeks of the treatment. Percentage of myeloid DCs (mDCs) in PBMC fraction was significantly lower in patients with both active and inactive GO, compared to patients with GD without GO and controls (p0.05). In the present study, we have succeeded to firstly demonstrate—according to our knowledge—that blood mDCs are negatively related to GO incidence

PIOM-FIPP: TN1

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PIOM-FIPP: Experimental Campaigns Design Report (ECD)

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PIOM-FIPP: Final Report (FR)

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