Onboarding of siponimod in secondary progressive multiple sclerosis patients in Australia: Novel, real-world evidence from the MSGo digital support programme.

Background: Siponimod is approved for use in people with secondary progressive multiple sclerosis (pwSPMS). An integrated digital platform, MSGo, was developed for pwSPMS and clinicians to help navigate the multiple steps of the pre-siponimod work-up. Objective: To explore real-world onboarding experiences of siponimod amongst pwSPMS in Australia. Methods: Retrospective, non-interventional, longitudinal, secondary analysis of data extracted from MSGo (20 April 2022). The primary endpoint was the average time for siponimod onboarding; secondary endpoints were adherence and sub-group analyses of variables influencing onboarding. Results: Mixed-cure modelling estimated that 58% of participants (N = 368, females 71%, median age of 59 years) registered in MSGo would ever initiate siponimod. The median time to initiation was 56 days (95% CI [47-59] days). Half of the participants cited 'waiting for vaccination' as the reason for initiation delay. Cox regression analyses found participants with a nominated care partner had faster onboarding (HR 2.1, 95% CI [1.5-3.0]) and were more likely to continue self-reporting daily siponimod dosing than were those without a care partner (HR 2.2, 95% CI [1.3-3.7]). Conclusions: Despite the limitations of self-reported data and the challenges of the COVID-19 pandemic, this study provides insights into siponimod onboarding in Australia and demonstrates the positive impact of care partner support.

A high-energy-resolution resonant inelastic X-ray scattering spectrometer at ID20 of the European Synchrotron Radiation Facility.

An end-station for resonant inelastic X-ray scattering and (resonant) X-ray emission spectroscopy at beamline ID20 of ESRF - The European Synchrotron is presented. The spectrometer hosts five crystal analysers in Rowland geometry for large solid angle collection and is mounted on a rotatable arm for scattering in both the horizontal and vertical planes. The spectrometer is optimized for high-energy-resolution applications, including partial fluorescence yield or high-energy-resolution fluorescence detected X-ray absorption spectroscopy and the study of elementary electronic excitations in solids. In addition, it can be used for non-resonant inelastic X-ray scattering measurements of valence electron excitations.

A large-solid-angle X-ray Raman scattering spectrometer at ID20 of the European Synchrotron Radiation Facility.

An end-station for X-ray Raman scattering spectroscopy at beamline ID20 of the European Synchrotron Radiation Facility is described. This end-station is dedicated to the study of shallow core electronic excitations using non-resonant inelastic X-ray scattering. The spectrometer has 72 spherically bent analyzer crystals arranged in six modular groups of 12 analyzer crystals each for a combined maximum flexibility and large solid angle of detection. Each of the six analyzer modules houses one pixelated area detector allowing for X-ray Raman scattering based imaging and efficient separation of the desired signal from the sample and spurious scattering from the often used complicated sample environments. This new end-station provides an unprecedented instrument for X-ray Raman scattering, which is a spectroscopic tool of great interest for the study of low-energy X-ray absorption spectra in materials under in situ conditions, such as in operando batteries and fuel cells, in situ catalytic reactions, and extreme pressure and temperature conditions.

Comparison of urinary odor-induced glomerular activation in the main olfactory bulb of aromatase knock-out and wild type female mice.

Previously [D.W. Wesson, M. Keller, Q. Douhard, M.J. Baum, J. Bakker, Enhanced urinary odor discrimination in female aromatase knockout mice, Horm. Behav. 49 (2006) 580-586] female aromatase knock out mice successfully learned to discriminate in a food-motivated go/no-go task between urinary volatiles from ovariectomized female mice treated with estradiol as opposed to estradiol plus progesterone whereas wild type females failed to learn this odor discrimination. We asked whether this behavioral difference is reflected in the ability of these two types of urinary volatiles to differentially stimulate Fos expression in juxtaglomerular cells (an index of glomerular activation) of the main olfactory bulb (MOB) in wild type versus ArKO female mice. Statistically significant differences in the profiles of MOB glomerular activation were seen in ovariectomized, estrogen-treated ArKO as well as WT female subjects following exposure to urinary volatiles from ovariectomized females given estradiol alone as opposed to estradiol plus progesterone. Therefore, previously observed differences between females of the two genotypes in their behavioral responses to these odors must reflect differential processing in more central segments of the olfactory pathway instead of in the MOB.

A multifocal symmetrical necrotising encephalomyelopathy in Angus calves.

OBJECTIVE: To define a neurological disorder in Angus calves. PROCEDURE: Clinical and pathological examinations were performed on affected Angus calves from a herd experiencing 1% annual mortality from neurological disease. CLINICAL SIGNS: Angus calves developed ataxia, nystagmus, strabismus, muscular tremors, opisthotonus, bruxism, hyperaesthesia, tetanic spasms and episodic convulsions at 2 to 6 weeks of age. Death occurred 4 to 7 days after the onset of clinical signs. GROSS PATHOLOGY: Bilaterally symmetrical, yellow-grey foci were present in the medulla oblongata. HISTOPATHOLOGY: Symmetrical degenerative lesions affected the dorsal vagal motor, lateral cuneate and olivary nuclei in the medulla oblongata and sometimes the spinal cord, substantia nigra and cerebellar peduncles. Malacia was characterised by spongiosis of the neuropile, vascular hyperplasia, infiltration of gitter cells, spheroid formation and delayed degeneration of neurones. CONCLUSION: Angus calves may develop a multifocal symmetrical necrotising encephalomyelopathy.

Role of the compact node and its posterior extension in normal atrioventricular nodal conduction, refractory, and dual pathway properties.

INTRODUCTION: The functional origin of AV nodal conduction, refractory, and dual pathway properties remains debated. The hypothesis that normal conduction and refractory properties of the compact node and its posterior nodal extension (PNE) play a critical role in the slow and the fast pathway, respectively, is tested with ablation lesions targeting these structures. METHODS AND RESULTS: A premature atrial stimulation protocol was performed before and after PNE ablation in six isolated rabbit heart preparations. Discrete (approximately 300 microm) histologically controlled PNE lesions amputated the AV nodal recovery curve from its left steep portion reflecting slow pathway conduction and prevented reentry without affecting the right smooth fast pathway portion of the curve. The ablation shortened A2H2max from 159 +/- 16 ms to 123 +/- 11 msec (P < 0.01) and prolonged the effective refractory period from 104 +/- 6 msec to 119 +/- 11 msec (P < 0.01) without affecting A2H2min (55 +/- 9 msec vs 55 +/- 8 msec; P = NS) and functional refractory period (174 +/- 7 msec vs 175 +/- 6 msec; P = NS). These results did not vary with the input reference used. In six other preparations, lesions applied to the compact node after PNE ablation shifted the fast pathway portion of the recovery curve to longer conduction times and prolonged the functional refractory period, suggesting a compact node involvement in the fast pathway. CONCLUSION: The normal AV nodal conduction and refractory properties reflect the net result of the interaction between a slow and a fast pathway, which primarily arise from the asymmetric properties of the PNE and compact node, respectively.

Characteristics, circuit, mechanism, and ablation of reentry in the rabbit atrioventricular node.

INTRODUCTION: The circuitry underlying AV nodal reentry remains debated. We developed a model of AV nodal reentry and assessed the role of nodal inputs, compact node, and its posterior nodal extension (PNE) in this phenomenon. METHODS AND RESULTS: A fine scanning of short coupling interval range with an atrial premature beat consistently initiated slow-fast AV nodal reentrant beats that occurred 37+/-31 msec (mean+/-SD) after His-bundle activation in 11 of 16 consecutive rabbit heart preparations. The repeated testing (>40 times) of a chosen coupling interval within reentry window (6+/-9 msec, n = 11) yielded reentrant intervals that varied by 2+/-1 msec (mean SD for 40 beats+/-SD, n = 11). The breakthrough point of reentrant activation, as assessed from four perinodal sites, varied in different preparations from diffuse (4) to anterior (1), medial (3), or posterior (3); mean reentrant interval did not differ between perinodal sites. Antegrade perinodal activation pattern did not differ at reentrant versus nonreentrant coupling intervals and thus was not a primary determinant of reentry. A PNE ablation (n = 4) interrupted the slow pathway conduction and prevented reentry without affecting antegrade perinodal activation or fast pathway conduction. CONCLUSION: A reproducible model of AV nodal reentrant beats was developed and used to study underlying circuitry. The AV nodal reentry involves unaltered antegrade perinodal activation, slow PNE conduction and retrograde broad invasion of perinodal tissues starting at a preparation-dependent breakthrough point. A PNE ablation abolishes the reentry.

X-ray Monochromator with 2 x 10(8) Energy Resolution.

An X-ray beam of 3 x 10(7) photons s(-1) with 2 x 10(8) relative energy resolution has been obtained at a third-generation synchrotron undulator X-ray source using the (13 13 13) Bragg reflection from a silicon perfect crystal. The production of these 25.70 keV X-rays with 450 +/- 50 mueV bandpass opens up new possibilities in X-ray optics and spectroscopies.