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Some X-ray free-electron laser facilities are pushing towards sub-10 fs pulses, making it desirable to reduce errors in X-ray/optical delay measurements to the 1 fs level. Researchers have now demonstrated X-ray measurements with a temporal resolution shorter than 1 fs, opening up new possibilities for time-resolved X-ray experiments. Today's brightest coherent X-ray sources, X-ray free-electron lasers, produce ultrafast X-ray pulses for which full-width at half-maximum durations as short as 3 fs have been measured 1 . There has been a marked increase in the popularity of such short pulses now that optical timing techniques have begun to report an X-ray/optical delay below ∼10 fs r.m.s. errors. As a result, sub-10 fs optical pulses have been implemented at the Linac Coherent Light Source (LCLS) X-ray beamlines, thus warranting a push to reduce the error in X-ray/optical delay measurements to the 1 fs level. Here, we report a unique two-dimensional spectrogram measurement of the relative X-ray/optical delay. This easily scalable relative delay measurement already surpasses previous techniques by an order of magnitude with its sub-1 fs temporal resolution and opens up the prospect of time-resolved X-ray measurements to the attosecond community.

Helium nanodroplets are considered ideal model systems to explore quantum hydrodynamics in self-contained, isolated superfluids. However, exploring the dynamic properties of individual droplets is experimentally challenging. In this work, we used single-shot femtosecond x-ray coherent diffractive imaging to investigate the rotation of single, isolated superfluid helium-4 droplets containing ~10⁸ to 1011 atoms. The formation of quantum vortex lattices inside the droplets is confirmed by observing characteristic Bragg patterns from xenon clusters trapped in the vortex cores. The vortex densities are up to five orders of magnitude larger than those observed in bulk liquid helium. The droplets exhibit large centrifugal deformations but retain axially symmetric shapes at angular velocities well beyond the stability range of viscous classical droplets.

Molecules can efficiently and selectively convert light energy into other degrees of freedom. Disentangling the underlying ultrafast motion of electrons and nuclei of the photoexcited molecule presents a challenge to current spectroscopic approaches. Here we explore the photoexcited dynamics of molecules by an interaction with an ultrafast X-ray pulse creating a highly localized core hole that decays via Auger emission. We discover that the Auger spectrum as a function of photoexcitation—X-ray-probe delay contains valuable information about the nuclear and electronic degrees of freedom from an element-specific point of view. For the nucleobase thymine, the oxygen Auger spectrum shifts towards high kinetic energies, resulting from a particular C–O bond stretch in the ππ* photoexcited state. A subsequent shift of the Auger spectrum towards lower kinetic energies displays the electronic relaxation of the initial photoexcited state within 200 fs. Ab-initio simulations reinforce our interpretation and indicate an electronic decay to the nπ* state. Photoexciting molecules provides insights into their different degrees of freedom if the ultrafast electron and nuclei motion can be properly analysed. To this end, McFarland et al. use X-ray pump-probe techniques to show that Auger spectra can unveil information on nuclear relaxation in molecules.

Background:In the Sint Maartenskliniek all rheumatoid arthritis (RA), psoriatic arthritis (PsA) or axial spondyloarthritis (axSpA) patients treated with etanercept biosimilar SB4 were transitioned to etanercept bio-originator. Transition was mandatory, but a rollback option was available in case of medically objective inefficacy or side-effects. For some patients this was their second transition, as in 2016, patients participated in a non-mandatory transition from etanercept bio-originator to that biosimilar. [1] Assessment of the effects of transitioning from the bio-originator to a biosimilar has been the focus of multiple studies and is generally accepted to be effective and safe. However, evidence on multiple transitions (including back to bio-originator) is very limited, sample sizes are small and data on specifically etanercept in rheumatic diseases is limited as well.Objectives:The aim of the current study is to investigate drug survival of etanercept bio-originator and changes in disease activity in patients who transitioned from biosimilar SB4 to bio-originator in 2022, and to assess differences between patients who previously had or had not used the bio-originator.Methods:A retrospective cohort study of patients with a clinical diagnosis of RA, PsA or axSpA who transitioned from etanercept biosimilar to etanercept bio-originator. We identified 2 sub cohorts, cohort 1: patients who transitioned for the first time (biosimilar to bio-originator) and cohort 2: patients who transitioned before (bio-originator to biosimilar to bio-originator). Data was extracted from electronic health records. Primary outcome was drug survival of etanercept bio-originator after the transition, analysed using multivariate cox regression analyses. Data was subdivided and tested for differences between cohort 1 and 2. Secondary outcomes included change in disease activity in six months after the transition, differences in this change between cohort 1 and 2 and reasons for treatment discontinuation with etanercept bio-originator. Lastly, drug survival of the current cohort was compared to drug survival in the previous cohort of the transition from etanercept bio-originator to etanercept biosimilar in 2016 and the 2014 reference cohort that was continuously treated with bio-originator. (1)Results:670 patients transitioned from biosimilar to bio-originator in 2022, of whom 274 belonged in cohort 1 and 396 in cohort 2. Patients in cohort 1 had significantly shorter disease duration, lower age, higher disease activity (only PsA and axSpA patients), more previous bDMARDs, shorter etanercept treatment duration and more often used etanercept in the standard dose (e.g. not tapered) compared to cohort 2 (Table 1). Overall drug survival at six months was 92% (95% CI 90-94%). For cohort 1 and 2 this was 87% (95% CI 82-90%) and 95% (95% CI 93-97%) respectively (Figure 1). Cohort 1 showed a non-significant higher risk of treatment discontinuation compared to cohort 2 (adjusted HR 1.28, [95% CI 0.57-2.86]). Reasons for discontinuation of treatment with bio-originator in Cohort 1 (n=32) and Cohort 2 (n=18) were perceived ineffectiveness (72% vs 78%) and perceived adverse events (28% vs 22%, mostly injection site reactions). Disease activity did not significantly differ between baseline and six months. The 2022 cohort showed, similar to the 2016 transition cohort, a significant higher risk of treatment discontinuation compared to the 2014 reference cohort that did not transition (HR 1.70, 95% CI 1.11 – 2.6, p-value < 0.05).Conclusion:Overall etanercept survival rates are high and disease activity measures are on a group level not affected by the transition. No significant differences were found between patients who previously had or had not used the bio-originator. Therefore, transitioning back and forth between biosimilar and bio-originator can be used in clinical practice to achieve cost-effective care.REFERENCES:[1] Tweehuysen L et al. Transitioning From Originator Etanercept to Biosimilar SB4: Six-Month Results From a Controlled Cohort Study. Arthritis and Rheumatology. 2018;70(9):1408-18.Acknowledgements:NIL.Disclosure of Interests:None declared.

La clarté de la langue française est un motif, à forte empreinte idéologique, qui depuis les premiers efforts d’émancipation de la langue jusqu’à l’époque contemporaine, a été mis en rapport avec l’esprit de la nation. Un survol historique de l’évolution complexe de la « clarté française » est complété par une analyse en synchronie, portant sur trois témoignages de l’année 1784 et montrant les divergences théoriques et méthodologiques dans l’approche de la notion de « clarté française ». The clarity of the French language is a motif, heavily marked by ideology, that has been linked with the spirit of the nation, beginning with the earliest efforts to emancipate the language all the way up to the present day. A historical overview of the complex evolution of “French clarity” is complemented by a synchronic analysis of three accounts from the year 1784, showing the theoretical and methodological divergences in approaching the notion of “French clarity.”

La clarté de la langue française est un motif, à forte empreinte idéologique, qui depuis les premiers efforts d’émancipation de la langue jusqu’à l’époque contemporaine, a été mis en rapport avec l’esprit de la nation Un survol historique de l’évolution complexe de la « clarté française » est complété par une analyse en synchronie, portant sur trois témoignages de l’année 1784 et montrant les divergences théoriques et méthodologiques dans l’approche de la notion de « clarté française »

Free electron laser (FEL) based x-ray sources show great promise for use in ultrafast molecular studies due to the short pulse durations and site/element sensitivity in this spectral range. However, the self amplified spontaneous emission (SASE) process mostly used in FELs is intrinsically noisy resulting in highly fluctuating beam parameters. Additionally timing synchronization of optical and FEL sources adds delay jitter in pump-probe experiments. We show how we mitigate the effects of source noise for the case of ultrafast molecular spectroscopy of the nucleobase thymine. Using binning and resorting techniques allows us to increase time and spectral resolution. In addition, choosing observables independent of noisy beam parameters enhances the signal fidelity.

Dans son Proiect du livre intitulé de la precedence du langage françois (1579), Henri Estienne compare trois langues néo-latines, le français, l'italien, l'espagnol, afin de montrer la supériorité du français. L'examen comparatif des langues est couplé avec une évaluation culturelle des trois nations. Les parametres de comparaison sont les qualités (gravité, grâce, richesse) des langues et de leurs locuteurs.