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Background Children with juvenile idiopathic arthritis (JIA) who achieve a drug free remission often experience a flare of their disease requiring either intraarticular steroids (IAS) or systemic treatment with disease modifying anti-rheumatic drugs (DMARDs). IAS offer an opportunity to recapture disease control and avoid exposure to side effects from systemic immunosuppression. We examined a cohort of patients treated with IAS after drug free remission and report the probability of restarting systemic treatment within 12 months. Methods We analyzed a cohort of patients from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry who received IAS for a flare after a period of drug free remission. Historical factors and clinical characteristics and of the patients including data obtained at the time of treatment were analyzed. Results We identified 46 patients who met the inclusion criteria. Of those with follow up data available 49% had restarted systemic treatment 6 months after IAS injection and 70% had restarted systemic treatment at 12 months. The proportion of patients with prior use of a biologic DMARD was the only factor that differed between patients who restarted systemic treatment those who did not, both at 6 months (79% vs 35%, p p Conclusion While IAS are an option for all patients who flare after drug free remission, it may not prevent the need to restart systemic treatment. Prior use of a biologic DMARD may predict lack of success for IAS. Those who previously received methotrexate only, on the other hand, are excellent candidates for IAS.

New classes of astronomical objects are often discovered serendipitously. The enormous data volumes produced by recent high-time resolution, radio-telescope surveys imply that efficient algorithms are required for a discovery. Such algorithms are usually tuned to detect specific, known sources. Existing data sets therefore likely contain unknown astronomical sources, which will remain undetected unless algorithms are developed that can detect a more diverse range of signals. We present the Single-dish PARKES data challenge for finding the uneXpected (SPARKESX), a compilation of real and simulated high-time resolution observations. SPARKESX comprises three mock surveys from the Parkes "Murriyang" radio telescope. A broad selection of simulated and injected expected signals (such as pulsars, fast radio bursts), poorly characterised signals (plausible flare star signatures) and unknown unknowns are generated for each survey. The goal of this challenge is to aid in the development of new algorithms that can detect a wide-range of source types. We show how successful a typical pipeline based on the standard pulsar search software, PRESTO, is at finding the injected signals. The dataset is publicly available at https://doi.org/10.25919/fd4f-0g20., Accepted for publication in MNRAS. 18 pages, 8 figures, 4 table

We present the results of a radio transient and polarisation survey towards the Galactic Centre, conducted as part of the Australian Square Kilometre Array Pathfinder Variables and Slow Transients pilot survey. The survey region consisted of five fields covering $\sim265\,{\rm deg}^2$ ($350^\circ\lesssim l\lesssim10^\circ$, $\vert b\vert \lesssim 10^\circ$). Each field was observed for 12\,minutes, with between 7 and 9 repeats on cadences of between one day and four months. We detected eight highly variable sources and seven highly circularly-polarised sources (14 unique sources in total). Seven of these sources are known pulsars including the rotating radio transient PSR~J1739--2521 and the eclipsing pulsar PSR~J1723--2837. One of them is a low mass X-ray binary, 4U 1758--25. Three of them are coincident with optical or infrared sources and are likely to be stars. The remaining three may be related to the class of Galactic Centre Radio Transients (including a highly likely one, VAST~J173608.2--321634, that has been reported previously), although this class is not yet understood. In the coming years, we expect to detect $\sim$40 bursts from this kind of source with the proposed four-year VAST survey if the distribution of the source is isotropic over the Galactic fields., 17 pages, 13 figures, Accepted for publication in MNRAS

ObjectiveDetermine the pharmacokinetics (PK) and exposure–response of hydroxychloroquine (HCQ) and desethylhydroxychloroquine (DHCQ) in paediatric SLE (pSLE).MethodsWe conducted an exploratory phase 2, direct-to-family trial. Children enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry with a diagnosis of pSLE were eligible if they were receiving HCQ as standard of care for ≥3 months. Biological samples were collected at up to four visits over a 6-month period. At each visit, plasma was obtained to measure the concentrations of HCQ and DHCQ, as well as cytokines. HCQ and DHCQ plasma PK data were analysed using a population PK modelling approach.ResultsTwenty-five subjects provided a total of 88 plasma concentrations for PK analysis. There was a poor linear fit between HCQ concentrations and total body weight (R2=0.03). There was a decline in both interferon (IFN)-alpha and IFN-gamma with higher concentrations of HCQ and DHCQ. Volume of distribution for HCQ in plasma was higher in children compared with published values in adults (73 000 L vs 44 000 L), but clearance values in children were similar to adults.ConclusionsWe report the first population PK model for HCQ and DHCQ in children using data from a novel direct-to-family clinical trial. We observed high interindividual variability in HCQ PK and found that weight-based dosing for HCQ is poorly correlated with drug concentrations, suggesting the need to use therapeutic drug monitoring to individualise dosing. Furthermore, our results suggest that the current weight-based dosing paradigm for HCQ may result in suboptimal drug exposures, particularly for children with obesity. Accordingly, additional studies of HCQ are needed in pSLE to determine the optimal drug concentration and dosing to reduce disease activity and improve outcomes.Trial registration numberNCT04358302.

Specialty training in plastic, reconstructive and aesthetic surgery is a prerequisite for safe and effective provision of care. The aim of this study was to assess and portray similarities and differences in the continuing education and specialization in plastic surgery in Europe.A detailed questionnaire was designed and distributed utilizing an online survey administration software. Questions addressed core items regarding continuing education and specialization in plastic surgery in Europe. Participants were addressed directly via the European Leadership Forum (ELF) of the European Society of Plastic, Reconstructive and Aesthetic Surgery (ESPRAS). All participants had detailed knowledge of the organization and management of plastic surgical training in their respective country.The survey was completed by 29 participants from 23 European countries. During specialization, plastic surgeons in Europe are trained in advanced tissue transfer and repair and aesthetic principles in all parts of the human body and within several subspecialties. Moreover, rotations in intensive as well as emergency care are compulsory in most European countries. Board certification is only provided for surgeons who have had multiple years of training regulated by a national board, who provide evidence of individually performed operative procedures in several anatomical regions and subspecialties, and who pass a final oral and/or written examination.Board certified plastic surgeons meet the highest degree of qualification, are trained in all parts of the body and in the management of complications. The standard of continuing education and qualification of European plastic surgeons is high, providing an excellent level of plastic surgical care throughout Europe.Die Facharzt-Weiterbildung für Plastische und Ästhetische Chirurgie ist eine Grundvoraussetzung für sichere und effektive Patientenversorgung. Ziel der vorliegenden Studie war die Darstellung von Gemeinsamkeiten und Unterschieden in der Weiterbildung für Plastische Chirurgie innerhalb von Europa.Ein internetbasierter Fragebogen wurde mit Hilfe eines kostenlosen Formularerstellungstools erstellt und verteilt. Die Fragen betrafen Kernpunkte der Weiterbildung für Plastische Chirurgie in Europa. Die Teilnehmer wurden direkt über das European Leadership Forum (ELF) der European Society of Plastic, Reconstructive and Aesthetic Surgery (ESPRAS) kontaktiert. Alle Teilnehmer hatten weitreichende Kenntnisse über die Organisation und Struktur der plastisch-chirurgischen Weiterbildung in ihrem jeweiligen Land.29 Teilnehmer*innen aus 23 europäischen Ländern nahmen an der Umfrage teil. Die Weiterbildung für Plastische Chirurgie beinhaltet grundlegende Prinzipien und Techniken zur Wiederherstellung von Form und Funktion innerhalb der verschiedenen Säulen der Plastischen Chirurgie, sowie in allen Körperregionen. In den meisten europäischen Ländern ist eine Rotation in der Intensiv- und Notfallmedizin und die Behandlung kritisch kranker Patienten obligatorisch. Voraussetzung für die Facharztbezeichnung ist die mehrjährige, national organisierte Weiterbildung, der Nachweis einer festgelegten Anzahl selbstständig durchgeführter Operationen, sowie die mündliche und/oder schriftliche Abschlussprüfung.Fachärzte für Plastische und Ästhetische Chirurgie sind hochqualifiziert und auch im Umgang mit Komplikationen geschult. Der Standard der Weiterbildung der europäischen Plastischen Chirurgen ist hoch, so dass innerhalb Europas eine hohe Qualität plastisch-chirurgischer Versorgung gewährleistet ist.

The number of patients with primary cutaneous lymphoma (PCL) relative to other non-Hodgkin lymphomas (NHLs) is small and the number of subtypes large. Although clinical trial guidelines have been published for mycosis fungoides/Sézary syndrome, the most common type of PCL, none exist for the other PCLs. In addition, staging of the PCLs has been evolving based on new data on potential prognostic factors, diagnosis, and assessment methods of both skin and extracutaneous disease and a desire to align the latter with the Lugano guidelines for all NHLs. The International Society for Cutaneous Lymphomas (ISCL), the United States Cutaneous LymphomaConsortium (USCLC), and the Cutaneous Lymphoma Task Force of the European Organization for the Research and Treatment of Cancer (EORTC) now propose updated staging and guidelines for the study design, assessment, endpoints, and response criteria in clinical trials for all the PCLs in alignment with that of the Lugano guidelines. These recommendations provide standardized methodology that should facilitate planning and regulatory approval of new treatments for these lymphomas worldwide, encourage cooperative investigator-initiated trials, and help to assess the comparative efficacy of therapeutic agents tested across sites and studies.

Observations of the extragalactic ($z=0.0141$) transient AT2018cow established a new class of energetic explosions shocking a dense medium, which produce luminous emission at millimeter and sub-millimeter wavelengths. Here we present detailed millimeter- through centimeter-wave observations of a similar transient, ZTF20acigmel (AT2020xnd) at $z=0.2433$. Using observations from the NOrthern Extended Millimeter Array and the Very Large Array, we model the unusual millimeter and radio emission from AT2020xnd under several different assumptions, and ultimately favor synchrotron radiation from a thermal electron population (relativistic Maxwellian). The thermal-electron model implies a fast but sub-relativistic ($v\approx0.3c$) shock and a high ambient density ($n_e\approx4\times10^{3}$cm$^{-3}$ at $\Delta t\approx40$ days). The X-ray luminosity of $L_X\approx10^{43}$ erg sec$^{-1}$ exceeds simple predictions from the radio and UVOIR luminosity and likely has a separate physical origin, such as a central engine. Using the fact that month-long luminous ($L_\nu\approx 2\times10^{30}$ erg sec$^{-1}$ Hz$^{-1}$ at 100 GHz) millimeter emission appears to be a generic feature of transients with fast ($t_{1/2}\approx3$ days) and luminous ($M_\mathrm{peak}\approx -21 $mag) optical light curves, we estimate the rate at which transients like AT2018cow and AT2020xnd will be detected by future wide-field millimeter transient surveys such as CMB-S4, and conclude that energetic explosions in dense environments may represent a significant population of extragalactic transients in the 100 GHz sky., Comment: 27 pages, 13 figures. Accepted for publication in ApJ on 23 Jan 2022