234 research outputs found

    Neural network interpolation of the magnetic field for the LISA Pathfinder Diagnostics Subsystem

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    LISA Pathfinder is a science and technology demonstrator of the European Space Agency within the framework of its LISA mission, which aims to be the first space-borne gravitational wave observatory. The payload of LISA Pathfinder is the so-called LISA Technology Package, which is designed to measure relative accelerations between two test masses in nominal free fall. Its disturbances are monitored and dealt by the diagnostics subsystem. This subsystem consists of several modules, and one of these is the magnetic diagnostics system, which includes a set of four tri-axial fluxgate magnetometers, intended to measure with high precision the magnetic field at the positions of the test masses. However, since the magnetometers are located far from the positions of the test masses, the magnetic field at their positions must be interpolated. It has been recently shown that because there are not enough magnetic channels, classical interpolation methods fail to derive reliable measurements at the positions of the test masses, while neural network interpolation can provide the required measurements at the desired accuracy. In this paper we expand these studies and we assess the reliability and robustness of the neural network interpolation scheme for variations of the locations and possible offsets of the magnetometers, as well as for changes in environmental conditions. We find that neural networks are robust enough to derive accurate measurements of the magnetic field at the positions of the test masses in most circumstances

    Comparative analysis of discrete exosome fractions obtained by differential centrifugation

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    Background: Cells release a mixture of extracellular vesicles, amongst these exosomes, that differ in size, density and composition. The standard isolation method for exosomes is centrifugation of fluid samples, typically at 100,000×g or above. Knowledge of the effect of discrete ultracentrifugation speeds on the purification from different cell types, however, is limited. Methods: We examined the effect of applying differential centrifugation g-forces ranging from 33,000×g to 200,000×g on exosome yield and purity, using 2 unrelated human cell lines, embryonic kidney HEK293 cells and bladder carcinoma FL3 cells. The fractions were evaluated by nanoparticle tracking analysis (NTA), total protein quantification and immunoblotting for CD81, TSG101, syntenin, VDAC1 and calreticulin. Results: NTA revealed the lowest background particle count in Dulbecco's Modified Eagle's Medium media devoid of phenol red and cleared by 200,000×g overnight centrifugation. The centrifugation tube fill level impacted the sedimentation efficacy. Comparative analysis by NTA, protein quantification, and detection of exosomal and contamination markers identified differences in vesicle size, concentration and composition of the obtained fractions. In addition, HEK293 and FL3 vesicles displayed marked differences in sedimentation characteristics. Exosomes were pelleted already at 33,000×g, a g-force which also removed most contaminating microsomes. Optimal vesicle-to-protein yield was obtained at 67,000×g for HEK293 cells but 100,000×g for FL3 cells. Relative expression of exosomal markers (TSG101, CD81, syntenin) suggested presence of exosome subpopulations with variable sedimentation characteristics. Conclusions: Specific g-force/k factor usage during differential centrifugation greatly influences the purity and yield of exosomes. The vesicle sedimentation profile differed between the 2 cell lines

    Microsatellite alteration and immunohistochemical expression profile of chromosome 9p21 in patients with sporadic renal cell carcinoma following surgical resection.

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    BACKGROUND: Long-term prognostic significance of loss of heterozygosity on chromosome 9p21 for localized renal cell carcinoma following surgery remains unreported. The study assessed the frequency of deletions of different loci of chromosome 9p along with immunohistochemical profile of proteins in surgically resected renal cancer tissue and correlated this with long-term outcomes. METHODS: DNA was extracted from renal tumours and corresponding normal kidney tissues in prospectively collected samples of 108 patients who underwent surgical resection for clinically localized disease between January 2001 and December 2005, providing a minimum of 9 years follow-up for each participant. After checking quality of DNA, amplified by PCR, loss of heterozygosity (LOH) on chromosome 9p was assessed using 6 microsatellite markers in 77 clear cell carcinoma. Only 5 of the markers showed LOH (D9S1814, D9S916, D9S974, D9S942, and D9S171). Protein expression of p15(INK4b), p16(INK4a), p14(ARF), CAIX, and adipose related protein (ADFP) were demonstrated by immunostaining in normal and cancer tissues. Loss of heterozygosity for microsatellite analysis was correlated with tumour characteristics, recurrence free, cancer specific, and overall survival, including significance of immunohistochemical profile of protein expressions. RESULTS: The main deletion was found at loci telomeric to CDKN2A region at D9S916. There was a significant correlation between frequency of LOH stage (p = 0.005) and metastases (p = 0.006) suggesting a higher LOH for advanced and aggressive renal cell carcinoma. Most commonly observed LOH in the 3 markers: D9S916, D9S974, and D9S942 were associated with poor survival, and were statistically significant on multivariate analysis. Immunohistochemical expression of p14, p15, and p16 proteins were either low or absent in cancer tissue compared to normal. CONCLUSIONS: Loss of heterozygosity of p921 chromosome is associated with aggressive tumours, and predicts cancer specific or recurrence free survival on long-term follow-up. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2514-8) contains supplementary material, which is available to authorized users

    Crit II Electric, Magnetic, and Density Measurements Within an Ionizing Neutral Stream

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    Measurements from rocket borne sensors inside a high velocity neutral barium beam show a factor of six increasei n plasmad ensityi n a movingi onizingf ront. This region-wacso -locatedw ith intensef luctuatinge lectric fields( $E • 300m V/m) at frequenciewse llu ndert he lower hybrid frequency for a barium plasina. Large quasi-DC electric and magnetic field fluctuations were also detected with a large componento f the current and the electricf ield. parallelt o Bo. An Alfv6n wavew ith a finite electricf ield componentp arallel to the geomagneticfi eld was observed to propagatea longB o, wherei t wasd etectedb y ami nstrumented sub-payload

    Propagation and dispersion of electrostatic waves in the ionospheric E region

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    Convection and electrodynamic signatures in the vicinity of a Sun-aligned arc: Results from the Polar Acceleration Regions and Convection Study (Polar ARCS)

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    An experimental campaign designed to study high-latitude auroral arcs was conducted in Sondre Stromfjord, Greenland, on February 26, 1987. The Polar Acceleration Regions and Convection Study (Polar ARCS) consisted of a coordinated set of ground-based, airborne, and sounding rocket measurements of a weak, sun-aligned arc system within the duskside polar cap. A rocket-borne barium release experiment, two DMSP satellite overflights, all-sky photography, and incoherent scatter radar measurements provided information on the large-scale plasma convection over the polar cap region while a second rocket instrumented with a DC magnetometer, Langmuir and electric field probes, and an electron spectrometer provided measurements of small-scale electrodynamics. The large-scale data indicate that small, sun-aligned precipitation events formed within a region of antisunward convection between the duskside auroral oval and a large sun-aligned arc further poleward. This convection signature, used to assess the relationship of the sun-aligned arc to the large-scale magnetospheric configuration, is found to be consistent with either a model in which the arc formed on open field lines on the dusk side of a bifurcated polar cap or on closed field lines threading an expanded low-latitude boundary layer, but not a model in which the polar cap arc field lines map to an expanded plasma sheet. The antisunward convection signature may also be explained by a model in which the polar cap arc formed on long field lines recently reconnected through a highly skewed plasma sheet. The small-scale measurements indicate the rocket passed through three narrow (less than 20 km) regions of low-energy (less than 100 eV) electron precipitation in which the electric and magnetic field perturbations were well correlated. These precipitation events are shown to be associated with regions of downward Poynting flux and small-scale upward and downward field-aligned currents of 1-2 micro-A/sq m. The paired field-aligned currents are associated with velocity shears (higher and lower speed streams) embedded in the region of antisunward flow

    Validity and reliability of the Danish and Swedish versions of the Bristol Rheumatoid Arthritis Fatigue questionnaires in patients with spondyloarthritis

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    ObjectiveTo investigate the validity, reliability, and interpretability of the Danish and Swedish versions of the Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire (BRAF-MDQ) and Bristol Rheumatoid Arthritis Fatigue Numerical Rating Scales (BRAF-NRS V2) (BRAFs) in patients with spondyloarthritis (SpA).MethodThe BRAFs were tested for validity and reliability in an online survey. Participants were identified in the national rheumatology databases.ResultsIn Denmark, 234/435 participants (53.8%) completed the first survey (T1), of whom 125 (82.2%) also completed the second survey (T2) (mean ± sd age 59.6 ± 13 years, 52.6% women). In Sweden, 183/420 participants (43.6%) completed T1, of whom 171 (93.4%) also completed T2 (age 54.7 ± 13 years, 62.3% female). In both Denmark and Sweden, the content validity was supported for the BRAFs; regarding structural validity for BRAF-MDQ, explanatory factor analysis identified five factors; Cronbach’s α (internal consistency) was 0.94/0.95 for BRAF-MDQ and 0.79–0.93/0.76–0.94 for the four subscales; intraclass correlation coefficients (ICCs) were 0.96/0.93 for BRAF-MDQ and 0.84–0.93/0.86–0.90 for the subscales, and ICCs of the three BRAF-NRS scales were 0.70–0.90/0.71–0.89; and Construct validity: 80% of the hypotheses were fulfilled for the BRAFs.ConclusionsGood content validity, acceptable construct validity, good reliability, and low degree of measurement error were found for BRAF-MDQ and BRAF-NRS V2. BRAF-MDQ had acceptable structural validity, but five factors were identified, instead of four, suggesting caution in distinguishing dimensions of fatigue. The BRAFs are considered valid and reliable for measuring fatigue in Danish and Swedish patients with SpA

    EULAR recommendations for the involvement of patient research partners in rheumatology research: 2023 update

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    BACKGROUND: Since the publication of the 2011 European Alliance of Associations for Rheumatology (EULAR) recommendations for patient research partner (PRP) involvement in rheumatology research, the role of PRPs has evolved considerably. Therefore, an update of the 2011 recommendations was deemed necessary. METHODS: In accordance with the EULAR Standardised Operational Procedures, a task force comprising 13 researchers, 2 health professionals and 10 PRPs was convened. The process included an online task force meeting, a systematic literature review and an in-person second task force meeting to formulate overarching principles (OAPs) and recommendations. The level of agreement of task force members was assessed anonymously (0-10 scale). RESULTS: The task force developed five new OAPs, updated seven existing recommendations and formulated three new recommendations. The OAPs address the definition of a PRP, the contribution of PRPs, the role of informal caregivers, the added value of PRPs and the importance of trust and communication in collaborative research efforts. The recommendations address the research type and phases of PRP involvement, the recommended number of PRPs per project, the support necessary for PRPs, training of PRPs and acknowledgement of PRP contributions. New recommendations concern the benefits of support and guidance for researchers, the need for regular evaluation of the patient-researcher collaboration and the role of a designated coordinator to facilitate collaboration. Agreements within the task force were high and ranged between 9.16 and 9.96. CONCLUSION: The updated EULAR recommendations for PRP involvement are more substantially based on evidence. Together with added OAPs, they should serve as a guide for researchers and PRPs and will ultimately strengthen the involvement of PRPs in rheumatology research

    Expert consensus statement on the treatment of immune-mediated inflammatory diseases with Janus kinase inhibitors: 2024 update

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    \ua9 2025 The Authors. In light of the introduction of new Janus kinase inhibitors (JAKi), new indications for JAKi and recent safety considerations that have arisen since the preceding consensus statement on JAKi therapy, a multidisciplinary taskforce was assembled, encompassing patients, health care professionals, and clinicians with expertise in JAKi therapy across specialties. This taskforce, informed by two comprehensive systematic literature reviews, undertook the objective to update the previous expert consensus for using JAKi developed in 2019. The taskforce deliberated on overarching principles, indications, dosage and comedication strategies, warnings and contraindications, screening protocols, monitoring recommendations, and adverse effect profiles. The methodology was based on the European Alliance of Associations for Rheumatology standard operating procedures, with voting on these important elements. Furthermore, an updated research agenda was proposed. The task force did not address when a JAKi should be prescribed but rather considerations once this decision has been made. This update aimed to equip clinicians with the necessary knowledge and guidance for the efficient and safe administration of this expanding and significant class of drugs
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