Modelling Jets, Tori and Flares in Pulsar Wind Nebulae

In this contribution we review the recent progress in the modelling of Pulsar Wind Nebulae (PWN). We start with a brief overview of the relevant physical processes in the magnetosphere, the wind-zone and the inflated nebula bubble. Radiative signatures and particle transport processes obtained from 3D simulations of PWN are discussed in the context of optical and X-ray observations. We then proceed to consider particle acceleration in PWN and elaborate on what can be learned about the particle acceleration from the dynamical structures called GwispsG observed in the Crab nebula. We also discuss recent observational and theoretical results of gamma-ray flares and the inner knot of the Crab nebula, which had been proposed as the emission site of the flares. We extend the discussion to GeV flares from binary systems in which the pulsar wind interacts with the stellar wind from a companion star. The chapter concludes with a discussion of solved and unsolved problems posed by PWN

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)

ULTRASAT: A wide-field time-domain UV space telescope

The Ultraviolet Transient Astronomy Satellite (ULTRASAT) is scheduled to be launched to geostationary orbit in 2026. It will carry a telescope with an unprecedentedly large field of view (204 deg$^2$) and NUV (230-290nm) sensitivity (22.5 mag, 5$\sigma$, at 900s). ULTRASAT will conduct the first wide-field survey of transient and variable NUV sources and will revolutionize our ability to study the hot transient universe: It will explore a new parameter space in energy and time-scale (months long light-curves with minutes cadence), with an extra-Galactic volume accessible for the discovery of transient sources that is $>$300 times larger than that of GALEX and comparable to that of LSST. ULTRASAT data will be transmitted to the ground in real-time, and transient alerts will be distributed to the community in $$23.5 AB mag, over 10 times deeper than the GALEX map. Two key science goals of ULTRASAT are the study of mergers of binaries involving neutron stars, and supernovae: With a large fraction ($>$50%) of the sky instantaneously accessible, fast (minutes) slewing capability and a field-of-view that covers the error ellipses expected from GW detectors beyond 2025, ULTRASAT will rapidly detect the electromagnetic emission following BNS/NS-BH mergers identified by GW detectors, and will provide continuous NUV light-curves of the events; ULTRASAT will provide early (hour) detection and continuous high (minutes) cadence NUV light curves for hundreds of core-collapse supernovae, including for rarer supernova progenitor types