7 research outputs found
Simultaneous 3D measurement of the translation and rotation of finite size particles and the flow field in a fully developed turbulent water flow
We report a novel experimental technique that measures simultaneously in
three dimensions the trajectories, the translation, and the rotation of finite
size inertial particles together with the turbulent flow. The flow field is
analyzed by tracking the temporal evolution of small fluorescent tracer
particles. The inertial particles consist of a super-absorbent polymer that
renders them index and density matched with water and thus invisible. The
particles are marked by inserting at various locations tracer particles into
the polymer. Translation and rotation, as well as the flow field around the
particle are recovered dynamically from the analysis of the marker and tracer
particle trajectories. We apply this technique to study the dynamics of
inertial particles much larger in size (Rp/{\eta} \approx 100) than the
Kolmogorov length scale {\eta} in a von K\'arm\'an swirling water flow
(R{\lambda} \approx 400). We show, using the mixed (particle/fluid) Eulerian
second order velocity structure function, that the interaction zone between the
particle and the flow develops in a spherical shell of width 2Rp around the
particle of radius Rp. This we interpret as an indication of a wake induced by
the particle. This measurement technique has many additional advantages that
will make it useful to address other problems such as particle collisions,
dynamics of non-spherical solid objects, or even of wet granular matter.Comment: 18 pages, 7 figures, submitted to "Measurement Science and
Technology" special issue on "Advances in 3D velocimetry
Modulation of Localized States in Electroconvection
We report on the effects of temporal modulation of the driving force on a
particular class of localized states, known as worms, that have been observed
in electroconvection in nematic liquid crystals. The worms consist of the
superposition of traveling waves and have been observed to have unique, small
widths, but to vary in length. The transition from the pure conduction state to
worms occurs via a backward bifurcation. A possible explanation of the
formation of the worms has been given in terms of coupled amplitude equations.
Because the worms consist of the superposition of traveling waves, temporal
modulation of the control parameter is a useful probe of the dynamics of the
system. We observe that temporal modulation increases the average length of the
worms and stabilizes worms below the transition point in the absence of
modulation.Comment: 4 pages, 4 figure
Tau-targeting antisense oligonucleotide MAPTRx in mild Alzheimer’s disease: a phase 1b, randomized, placebo-controlled trial
Tau plays a key role in Alzheimer’s disease (AD) pathophysiology, and accumulating evidence suggests that lowering tau may reduce this pathology. We sought to inhibit MAPT expression with a tau-targeting antisense oligonucleotide (MAPTRx) and reduce tau levels in patients with mild AD. A randomized, double-blind, placebo-controlled, multiple-ascending dose phase 1b trial evaluated the safety, pharmacokinetics and target engagement of MAPTRx. Four ascending dose cohorts were enrolled sequentially and randomized 3:1 to intrathecal bolus administrations of MAPTRx or placebo every 4 or 12 weeks during the 13-week treatment period, followed by a 23 week post-treatment period. The primary endpoint was safety. The secondary endpoint was MAPTRx pharmacokinetics in cerebrospinal fluid (CSF). The prespecified key exploratory outcome was CSF total-tau protein concentration. Forty-six patients enrolled in the trial, of whom 34 were randomized to MAPTRx and 12 to placebo. Adverse events were reported in 94% of MAPTRx-treated patients and 75% of placebo-treated patients; all were mild or moderate. No serious adverse events were reported in MAPTRx-treated patients. Dose-dependent reduction in the CSF total-tau concentration was observed with greater than 50% mean reduction from baseline at 24 weeks post-last dose in the 60 mg (four doses) and 115 mg (two doses) MAPTRx groups. Clinicaltrials.gov registration number: NCT03186989
Effectiveness and safety of opicapone in Parkinson’s disease patients with motor fluctuations: the OPTIPARK open-label study
Background The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials. Methods OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Results Of the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p < 0.0001) and motor scores during ON (− 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of − 3.4 ± 12.8 points for PDQ-8 and -6.8 ± 19.7 points for NMSS were statistically significant versus baseline (both p < 0.0001). Most of TEAEs (94.8% of events) were of mild or moderate intensity. TEAEs considered to be at least possibly related to opicapone were reported for 45.1% of patients, with dyskinesia (11.5%) and dry mouth (6.5%) being the most frequently reported. Serious TEAEs considered at least possibly related to opicapone were reported for 1.4% of patients. Conclusions Opicapone 50 mg was effective and generally well-tolerated in PD patients with motor fluctuations treated in clinical practice. Trial registration Registered in July 2016 at clinicaltrials.gov (NCT02847442)
Tau-targeting antisense oligonucleotide MAPTRx in mild Alzheimer’s disease: a phase 1b, randomized, placebo-controlled trial
Tau plays a key role in Alzheimer’s disease (AD) pathophysiology, and accumulating evidence suggests that lowering tau may reduce this pathology. We sought to inhibit MAPT expression with a tau-targeting antisense oligonucleotide (MAPTRx) and reduce tau levels in patients with mild AD. A randomized, double-blind, placebo-controlled, multiple-ascending dose phase 1b trial evaluated the safety, pharmacokinetics and target engagement of MAPTRx. Four ascending dose cohorts were enrolled sequentially and randomized 3:1 to intrathecal bolus administrations of MAPTRx or placebo every 4 or 12 weeks during the 13-week treatment period, followed by a 23 week post-treatment period. The primary endpoint was safety. The secondary endpoint was MAPTRx pharmacokinetics in cerebrospinal fluid (CSF). The prespecified key exploratory outcome was CSF total-tau protein concentration. Forty-six patients enrolled in the trial, of whom 34 were randomized to MAPTRx and 12 to placebo. Adverse events were reported in 94% of MAPTRx-treated patients and 75% of placebo-treated patients; all were mild or moderate. No serious adverse events were reported in MAPTRx-treated patients. Dose-dependent reduction in the CSF total-tau concentration was observed with greater than 50% mean reduction from baseline at 24 weeks post-last dose in the 60 mg (four doses) and 115 mg (two doses) MAPTRx groups. Clinicaltrials.gov registration number: NCT03186989
Hyperon signatures in the PANDA experiment at FAIR
We present a detailed simulation study of the signatures from the sequential decays of the triple-strange pbar p -> Ω+Ω- -> K+ΛbarK- Λ -> K+pbarπ+K-pπ- process in the PANDA central tracking system with focus on hit patterns and precise time measurement. We present a systematic approach for studying physics channels at the detector level and develop input criteria for tracking algorithms and trigger lines. Finally, we study the beam momentum dependence on the reconstruction efficiency for the PANDA detector