Pain Reduction in Adults with Limb Spasticity Following Treatment with IncobotulinumtoxinA: a Pooled Analysis

Some studies have shown that incobotulinumtoxinA reduces spasticity-associated pain, but further evidence is needed. This exploratory analysis pooled pain-relief data from six Phase 2 or 3 studies of incobotulinumtoxinA (four placebo-controlled studies) for treating upper limb spasticity in adults. Spasticity-associated pain was assessed at baseline and 4 weeks post incobotulinumtoxinA injection using the disability assessment scale (DAS) for pain. Only data for patients with pain at baseline were analysed. Overall, 544 (incobotulinumtoxinA, N = 415; placebo, N = 129) of 937 patients (58.1%) experienced pain at baseline. At Week 4, a significantly greater proportion of incobotulinumtoxinA- (52.1%) than placebo-treated patients (28.7%; Chi-square p < 0.0001) showed a response (≥1-point improvement in DAS pain score). In logistic regression analysis, incobotulinumtoxinA-treated patients were 2.6 times more likely to achieve this endpoint than placebo-treated patients. A significant difference between incobotulinumtoxinA and placebo was observed regardless of baseline pain severity. Additionally, 27.1% of incobotulinumtoxinA- versus 12.4% of placebo-treated patients reported complete pain relief at Week 4 (p = 0.0006). Pain relief increased with multiple injection cycles. To achieve patient-centred care, pain relief may be considered a treatment goal in adults with spasticity-associated pain regardless of pain severity. This study contributes to understanding the benefits of incobotulinumtoxinA in treating limb spasticity-associated pain.info:eu-repo/semantics/publishedVersio

Relationship between reproductive hormones and migration distance in a polygynous songbird, the Red‑winged Blackbird (\u3ci\u3eAgelaius phoeniceus\u3c/i\u3e)

Many bird species migrate to southern overwintering locations to avoid harsh conditions at their breeding grounds, but at the cost of an energetically demanding migration that may delay their spring reproductive development. Previous work on the relationship between migration distance and reproductive readiness has primarily focused on early season baseline testosterone in both males and females. However, for females, testosterone alone may not be the appropriate measurement of reproductive development. Estradiol, a metabolite of testosterone that is essential for breeding behaviors and reproduction, should also be measured. Furthermore, baseline testosterone varies throughout the day and may change due to social interactions that occurred prior to sampling. Injection of gonadotropin-releasing hormone (GnRH) elicits an individual’s maximum potential testosterone production, minimizing daily and social variation. We explored relationships between migration distance and reproductive status after arrival to the breeding ground in Red-winged Blackbirds (Agelaius phoeniceus). We predicted that individuals that travel a shorter distance will have higher levels of reproductive hormones upon arrival given they are able to invest less in migration and more in reproduction. This is important because individuals that breed earlier often have higher reproductive success. In females, we measured baseline estradiol and testosterone. In males, we assessed baseline and GnRH-induced testosterone. Hormone values were related to migration distance, estimated by stable isotope analysis of claw samples collected before breeding began in eastern North Dakota. We found that males with shorter inferred migration distances have higher baseline testosterone upon arrival. However, inferred migration distance was not correlated with GnRH-induced testosterone. Female inferred migration distance was not correlated with baseline testosterone, but it was correlated with baseline estradiol. Females with higher testosterone had lower estradiol, suggesting that testosterone in females is not a reliable indicator of estradiol levels, thus readiness to breed. Our observations suggest that baseline hormone levels were related to migration distance, but baseline testosterone alone may not provide a complete assessment of a male or female’s preparedness to breed following spring migration

The influence of laser relative intensity noise in the Laser Interferometer Space Antenna

LISA is an upcoming ESA mission that will detect gravitational waves in spaceby interferometrically measuring the separation between free-falling testmasses at picometer precision. To reach the desired performance, LISA willemploy the noise reduction technique time-delay interferometry (TDI), in whichmultiple raw interferometric readouts are time shifted and combined into thefinal scientific observables. Evaluating the performance in terms of these TDIvariables requires careful tracking of how different noise sources propagatethrough TDI, as noise correlations might affect the performance in unexpectedways. One example of such potentially correlated noise is the relativeintensity noise (RIN) of the six lasers aboard the three LISA satellites, whichwill couple into the interferometric phase measurements. In this article, wecalculate the expected RIN levels based on the current mission architecture andthe envisaged mitigation strategies. We find that strict requirements on thetechnical design reduce the effect from approximately 8.7 pm/rtHz perinter-spacecraft interferometer to that of a much lower sub-1 pm/rtHz noise,with typical characteristics of an uncorrelated readout noise after TDI. Ourinvestigations underline the importance of sufficient balanced detection of theinterferometric measurements.<br

Picosecond timing of Microwave Cherenkov Impulses from High-Energy Particle Showers Using Dielectric-loaded Waveguides

We report on the first measurements of coherent microwave impulses from high-energy particle-induced electromagnetic showers generated via the Askaryan effect in a dielectric-loaded waveguide. Bunches of 12.16 GeV electrons with total bunch energy of $\sim 10^3-10^4$ GeV were pre-showered in tungsten, and then measured with WR-51 rectangular (12.6 mm by 6.3 mm) waveguide elements loaded with solid alumina ($Al_2 O_3$) bars. In the 5-8 GHz $TE_{10}$ single-mode band determined by the presence of the dielectric in the waveguide, we observed band-limited microwave impulses with amplitude proportional to bunch energy. Signals in different waveguide elements measuring the same shower were used to estimate relative time differences with 2.3 picosecond precision. These measurements establish a basis for using arrays of alumina-loaded waveguide elements, with exceptional radiation hardness, as very high precision timing planes for high-energy physics detectors.Comment: 16 pages, 15 figure

Measurements and Modeling of Near-Surface Radio Propagation in Glacial Ice and Implications for Neutrino Experiments

We present measurements of radio transmission in the $\sim$100 MHz range through a $\sim100$ m deep region below the surface of the ice at Summit Station, Greenland, called the firn. In the firn, the index of refraction changes due to the transition from snow at the surface to glacial ice below, affecting the propagation of radio signals in that region. We compare our observations to a finite-difference time-domain (FDTD) electromagnetic wave simulation, which supports the existence of three classes of propagation: a bulk propagation ray-bending mode that leads to so-called "shadowed" regions for certain geometries of transmission, a surface-wave mode induced by the ice/air interface, and an arbitrary-depth horizontal propagation mode that requires perturbations from a smooth density gradient. In the non-shadowed region, our measurements are consistent with the bulk propagation ray-bending mode both in timing and in amplitude. We also observe signals in the shadowed region, in conflict with a bulk-propagation-only ray-bending model, but consistent with FDTD simulations using a variety of firn models for Summit Station. The amplitude and timing of our measurements in all geometries are consistent with the predictions from FDTD simulations. In the shadowed region, the amplitude of the observed signals is consistent with a best-fit coupling fraction value of $2.4$% (0.06% in power) or less to a surface or horizontal propagation mode from the bulk propagation mode. The relative amplitude of observable signals in the two regions is important for experiments that aim to detect radio emission from astrophysical high-energy neutrinos interacting in glacial ice, which rely on a radio propagation model to inform simulations and perform event reconstruction.Comment: 14 pages, 13 figures, version accepted to PR

The bioavailability of oral GI147211 (GG211), a new topoisomerase I inhibitor.

Topoisomerase I inhibitors are new compounds of interest for cancer chemotherapy. We performed a study with GI147211, a new semisynthetic camptothecin analogue, to determine the absolute bioavailability of the drug given orally. Patients with a histologically confirmed diagnosis of a solid tumour refractory to standard forms of therapy were eligible for the study. GI147211 was given orally on day 1 and as a 30-min infusion daily on days 2-5. The treatment course was repeated every 3 weeks. In subsequent patient cohorts, the dose of the oral formulation was escalated from 1.5 mg m(-2) to 6.0 mg m(-2); the dose for i.v. administration was fixed at 1.2 mg m(-2). Plasma pharmacokinetics was performed on day 1 and 2 of the first course and on day 1 of the second course using a validated high-performance liquid chromatographic assay. Nineteen patients were entered into the study; one patient was not evaluable because the treatment course was stopped prematurely. Eighteen patients received a total of 47 treatment courses. The absolute bioavailability of GI147211 averaged 1.3 +/- 5.2%. Drug appeared quickly in plasma with a median Tmax at 0.5 h. Fasting or fed state had no significant influence on the bioavailability of GI147211. The terminal half-life after administration of oral GI147211 was 6.85 +/- 3.13 h, similar to the half-life after intravenous administration. The major toxicities were neutropenia and thrombocytopenia. Nadirs for neutropenia and thrombocytopenia occurred on day 8 and day 15 respectively. Other toxicities predominantly consisted of mild and infrequent nausea and vomiting, and fatigue. The oral administration of the drug is well tolerated. Oral administration of topoisomerase I inhibitor GI147211 results in a low bioavailability with relatively wide interpatient variation. The intravenous route of administration is advised for further development of this promising topoisomerase I inhibitor

Development Toward a Ground-Based Interferometric Phased Array for Radio Detection of High Energy Neutrinos

The in-ice radio interferometric phased array technique for detection of high energy neutrinos looks for Askaryan emission from neutrinos interacting in large volumes of glacial ice, and is being developed as a way to achieve a low energy threshold and a large effective volume at high energies. The technique is based on coherently summing the impulsive Askaryan signal from multiple antennas, which increases the signal-to-noise ratio for weak signals. We report here on measurements and a simulation of thermal noise correlations between nearby antennas, beamforming of impulsive signals, and a measurement of the expected improvement in trigger efficiency through the phased array technique. We also discuss the noise environment observed with an analog phased array at Summit Station, Greenland, a possible site for an interferometric phased array for radio detection of high energy neutrinos.Comment: 13 Pages, 14 Figure

Accelerator measurements of magnetically-induced radio emission from particle cascades with applications to cosmic-ray air showers

For fifty years, cosmic-ray air showers have been detected by their radio emission. We present the first laboratory measurements that validate electrodynamics simulations used in air shower modeling. An experiment at SLAC provides a beam test of radio-frequency (RF) radiation from charged particle cascades in the presence of a magnetic field, a model system of a cosmic-ray air shower. This experiment provides a suite of controlled laboratory measurements to compare to particle-level simulations of RF emission, which are relied upon in ultra-high-energy cosmic-ray air shower detection. We compare simulations to data for intensity, linearity with magnetic field, angular distribution, polarization, and spectral content. In particular, we confirm modern predictions that the magnetically induced emission in a dielectric forms a cone that peaks at the Cherenkov angle and show that the simulations reproduce the data within systematic uncertainties.Comment: 5 pages, 7 figure