European expert consensus statement on the systemic treatment of alopecia areata.

Alopecia areata is an autoimmune form of non-scarring hair loss. It is usually characterized by limited areas of hair loss. However, the disease may progress to complete scalp and body hair loss (alopecia totalis, alopecia universalis). In patients with alopecia areata hair loss significantly impacts the quality of life. Children and adolescents with alopecia areata often experience bullying, including physical aggression. The disease severity evaluation tools used in clinical practice are: the Severity of Alopecia Tool (SALT) score and the Alopecia Areata Scale (AAS). A SALT score equal to or greater than 20 constitutes a commonly accepted indication for systemic therapy in alopecia areata. When using the AAS, moderate to severe alopecia areata should be considered a medical indication for systemic treatment. Currently, the only two EMA-approved medications for alopecia areata are baricitinib (JAK 1/2 inhibitor) for adults and ritlecitinib (JAK 3/TEC inhibitor) for individuals aged 12 and older. Both are EMA-approved for patients with severe alopecia areata. Other systemic medications used off-label in alopecia areata include glucocorticosteroids, cyclosporine, methotrexate and azathioprine. Oral minoxidil is considered an adjuvant therapy with limited data confirming its possible efficacy. This consensus statement is to outline a systemic treatment algorithm for alopecia areata, indications for systemic treatment, available therapeutic options, their efficacy and safety, as well as the duration of the therapy.

Investigating charge-up and fragmentation dynamics of oxygen molecules after interaction with strong X-ray free-electron laser pulses.

During the last decade, X-ray free-electron lasers (XFELs) have enabled the study of light-matter interaction under extreme conditions. Atoms which are subject to XFEL radiation are charged by a complex interplay of (several subsequent) photoionization events and electronic decay processes within a few femtoseconds. The interaction with molecules is even more intriguing, since intricate nuclear dynamics occur as the molecules start to dissociate during the charge-up process. Here, we demonstrate that by analyzing photoelectron angular emission distributions and kinetic energy release of charge states of ionic molecular fragments, we can obtain a detailed understanding of the charge-up and fragmentation dynamics. Our novel approach allows for gathering such information without the need of complex ab initio modeling. As an example, we provide a detailed view on the processes happening on a femtosecond time scale in oxygen molecules exposed to intense XFEL pulses.

Guidelines for clinical trials of frontal fibrosing alopecia: consensus recommendations from the International FFA Cooperative Group (IFFACG).

BACKGROUND: Frontal fibrosing alopecia (FFA) has become one of the most common causes of cicatricial alopecia worldwide. However, there is a lack of clear aetiology and robust clinical trial evidence for the efficacy and safety of agents currently used for treatment. OBJECTIVES: To enable data to be collected worldwide on FFA using common criteria and assessment methods. METHODS: A multicentre, international group of experts in hair loss was convened by email to create consensus recommendations for clinical trials. Consensus was defined at > 90% agreement on each recommended part of these guidelines. RESULTS: Standardized diagnostic criteria, severity rating, staging, and investigator and patient assessment of scalp hair loss and other clinical features of FFA were created. CONCLUSIONS: These guidelines should allow the collection of reliable aggregate data on FFA and advance efforts in both clinical and basic research to close knowledge gaps in this condition.

Photon-recoil imaging: Expanding the view of nonlinear x-ray physics.

Addressing the ultrafast coherent evolution of electronic wave functions has long been a goal of nonlinear x-ray physics. A first step toward this goal is the investigation of stimulated x-ray Raman scattering (SXRS) using intense pulses from an x-ray free-electron laser. Earlier SXRS experiments relied on signal amplification during pulse propagation through dense resonant media. By contrast, our method reveals the fundamental process in which photons from the primary radiation source directly interact with a single atom. We introduce an experimental protocol in which scattered neutral atoms rather than scattered photons are detected. We present SXRS measurements at the neon K edge and a quantitative theoretical analysis. The method should become a powerful tool in the exploration of nonlinear x-ray physics.

Ultrafast relaxation of photoexcited superfluid He nanodroplets.

The relaxation of photoexcited nanosystems is a fundamental process of light-matter interaction. Depending on the couplings of the internal degrees of freedom, relaxation can be ultrafast, converting electronic energy in a few fs, or slow, if the energy is trapped in a metastable state that decouples from its environment. Here, we study helium nanodroplets excited resonantly by femtosecond extreme-ultraviolet (XUV) pulses from a seeded free-electron laser. Despite their superfluid nature, we find that helium nanodroplets in the lowest electronically excited states undergo ultrafast relaxation. By comparing experimental photoelectron spectra with time-dependent density functional theory simulations, we unravel the full relaxation pathway: Following an ultrafast interband transition, a void nanometer-sized bubble forms around the localized excitation (He[Formula: see text]) within 1 ps. Subsequently, the bubble collapses and releases metastable He[Formula: see text] at the droplet surface. This study highlights the high level of detail achievable in probing the photodynamics of nanosystems using tunable XUV pulses.

Time-Resolved Measurement of Interatomic Coulombic Decay Induced by Two-Photon Double Excitation of Ne_{2}.

The hitherto unexplored two-photon doubly excited states [Ne^{*}(2p^{-1}3s)]_{2} were experimentally identified using the seeded, fully coherent, intense extreme ultraviolet free-electron laser FERMI. These states undergo ultrafast interatomic Coulombic decay (ICD), which predominantly produces singly ionized dimers. In order to obtain the rate of ICD, the resulting yield of Ne_{2}^{+} ions was recorded as a function of delay between the extreme ultraviolet pump and UV probe laser pulses. The extracted lifetimes of the long-lived doubly excited states, 390(-130/+450) fs, and of the short-lived ones, less than 150 fs, are in good agreement with ab initio quantum mechanical calculations.

Circular Dichroism in Multiphoton Ionization of Resonantly Excited He

Intense, circularly polarized extreme-ultraviolet and near-infrared (NIR) laser pulses are combined to double ionize atomic helium via the oriented intermediate He^{+}(3p) resonance state. Applying angle-resolved electron spectroscopy, we find a large photon helicity dependence of the spectrum and the angular distribution of the electrons ejected from the resonance by NIR multiphoton absorption. The measured circular dichroism is unexpectedly found to vary strongly as a function of the NIR intensity. The experimental data are well described by theoretical modeling and possible mechanisms are discussed.

Slow Interatomic Coulombic Decay of Multiply Excited Neon Clusters.

Ne clusters (∼5000 atoms) were resonantly excited (2p→3s) by intense free electron laser (FEL) radiation at FERMI. Such multiply excited clusters can decay nonradiatively via energy exchange between at least two neighboring excited atoms. Benefiting from the precise tunability and narrow bandwidth of seeded FEL radiation, specific sites of the Ne clusters were probed. We found that the relaxation of cluster surface atoms proceeds via a sequence of interatomic or intermolecular Coulombic decay (ICD) processes while ICD of bulk atoms is additionally affected by the surrounding excited medium via inelastic electron scattering. For both cases, cluster excitations relax to atomic states prior to ICD, showing that this kind of ICD is rather slow (picosecond range). Controlling the average number of excitations per cluster via the FEL intensity allows a coarse tuning of the ICD rate.

High resolution multiphoton spectroscopy by a tunable free-electron-laser light.

Seeded free electron lasers theoretically have the intensity, tunability, and resolution required for multiphoton spectroscopy of atomic and molecular species. Using the seeded free electron laser FERMI and a novel detection scheme, we have revealed the two-photon excitation spectra of dipole-forbidden doubly excited states in helium. The spectral profiles of the lowest (-1,0)(+1) (1)S(e) and (0,1)(0) (1)D(e) resonances display energy shifts in the meV range that depend on the pulse intensity. The results are explained by an effective two-level model based on calculated Rabi frequencies and decay rates.

Hidden charge states in soft-x-ray laser-produced nanoplasmas revealed by fluorescence spectroscopy.

Highly charged ions are formed in the center of composite clusters by strong free-electron laser pulses and they emit fluorescence on a femtosecond time scale before competing recombination leads to neutralization of the nanoplasma core. In contrast to mass spectrometry that detects remnants of the interaction, fluorescence in the extreme ultraviolet spectral range provides fingerprints of transient states of high energy density matter. Spectra from clusters consisting of a xenon core and a surrounding argon shell show that a small fraction of the fluorescence signal comes from multiply charged xenon ions in the cluster core. Initially, these ions are as highly charged as the ions in the outer shells of pure xenon clusters with charge states up to at least 11+.

Determining the polarization state of an extreme ultraviolet free-electron laser beam using atomic circular dichroism.

Ultrafast extreme ultraviolet and X-ray free-electron lasers are set to revolutionize many domains such as bio-photonics and materials science, in a manner similar to optical lasers over the past two decades. Although their number will grow steadily over the coming decade, their complete characterization remains an elusive goal. This represents a significant barrier to their wider adoption and hence to the full realization of their potential in modern photon sciences. Although a great deal of progress has been made on temporal characterization and wavefront measurements at ultrahigh extreme ultraviolet and X-ray intensities, only few, if any progress on accurately measuring other key parameters such as the state of polarization has emerged. Here we show that by combining ultra-short extreme ultraviolet free electron laser pulses from FERMI with near-infrared laser pulses, we can accurately measure the polarization state of a free electron laser beam in an elegant, non-invasive and straightforward manner using circular dichroism.

Novel collective autoionization process observed in electron spectra of He clusters.

The ionization dynamics of He nanodroplets irradiated with intense femtosecond extreme ultraviolet pulses of up to 1013 W/cm2 power density have been investigated by photoelectron spectroscopy. Helium droplets were resonantly excited to atomiclike 2p states with a photon energy of 21.4 eV, below the ionization potential (Ip), and directly into the ionization continuum with 42.8 eV photons. While electron emission following direct ionization above Ip is well explained within a model based on a sequence of direct electron emission events, the resonant excitation provides evidence of a new, collective ionization mechanism involving many excited atomiclike 2p states. With increasing power density the direct photoline due to an interatomic Coulombic decay disappears. It indicates that ionization occurs due to energy exchange between at least three excited atoms proceeding on a femtosecond time scale. In agreement with recent theoretical work the novel ionization process is very efficient and it is expected to be important for many other systems.

Collective autoionization in multiply-excited systems: a novel ionization process observed in helium nanodroplets.

Free electron lasers (FELs) offer the unprecedented capability to study reaction dynamics and image the structure of complex systems. When multiple photons are absorbed in complex systems, a plasma-like state is formed where many atoms are ionized on a femtosecond timescale. If multiphoton absorption is resonantly-enhanced, the system becomes electronically-excited prior to plasma formation, with subsequent decay paths which have been scarcely investigated to date. Here, we show using helium nanodroplets as an example that these systems can decay by a new type of process, named collective autoionization. In addition, we show that this process is surprisingly efficient, leading to ion abundances much greater than that of direct single-photon ionization. This novel collective ionization process is expected to be important in many other complex systems, e.g. macromolecules and nanoparticles, exposed to high intensity radiation fields.

Resonant Auger spectroscopy at the carbon and nitrogen K-edges of pyrimidine.

The resonant Auger electron spectra obtained after photoexcitation below the C and N 1s ionization thresholds in the pyrimidine molecule have been measured at several photon energies. The results show the relevance of the localization of the inner hole and of the matching between the symmetries of the intermediate and final states in the decay spectra via participator transitions. The comparison with the Auger electron spectra suggests some assignment for the two-hole-one-particle states reached via spectator transitions. The analysis of the participator decay is supported by state-of-the art density functional theory calculations.

Vibrationally resolved photoionization of N2 near threshold.

A recently developed velocity map imaging spectrometer has been used to study the photoionization of molecular nitrogen near threshold. The potentialities of the spectrometer have been exploited to measure simultaneously the energy and angular distribution of the photoelectrons corresponding to the residual N(2)(+) X(2)Σ(g) v = 0-3 ion states. In a single experiment all the experimental observables, i.e., the total and partial cross sections, their branching ratios and the asymmetry parameter of the angular distributions have been determined.

A photoelectron velocity map imaging spectrometer for experiments combining synchrotron and laser radiations.

A velocity map imaging/ion time-of-flight spectrometer designed specifically for pump-probe experiments combining synchrotron and laser radiations is described. The in-house built delay line detector can be used in two modes: the high spatial resolution mode and the coincidence mode. In the high spatial resolution mode a kinetic energy resolution of 6% has been achieved. The coincidence mode can be used to improve signal-to-noise ratio for the pump-probe experiments either by using a gate to count electrons only when the laser is present or by recording coincidences with the ion formed in the ionization process.

Pyrimidine and halogenated pyrimidines near edge x-ray absorption fine structure spectra at C and N K-edges: experiment and theory.

The inner shell excitation of pyrimidine and some halogenated pyrimidines near the C and N K-edges has been investigated experimentally by near edge x-ray absorption fine structure spectroscopy and theoretically by density functional theory calculations. The selected targets, 5-Br-pyrimidine, 2-Br-pyrimidine, 2-Cl-pyrimidine, and 5-Br-2-Cl-pyrimidine, allow the effects of the functionalization of the pyrimidine ring to be studied either as a function of different halogen atoms bound to the same molecular site or as a function of the same halogen atom bound to different molecular sites. The results show that the individual characteristics of the different spectra of the substituted pyrimidines can be rationalized in terms of variations in electronic and geometrical structures of the molecule depending on the localization and the electronegativity of the substituent.

Investigation of halogenated pyrimidines by X-ray photoemission spectroscopy and theoretical DFT methods.

The inner shell ionization of pyrimidine and some halogenated pyrimidines has been investigated experimentally by X-ray photoemission spectroscopy (XPS) and theoretically by density functional theory (DFT) methods. The selected targets-5-Br-pyrimidine, 2-Br-pyrimidine, 2-Cl-pyrimidine, and 5-Br-2-Cl-pyrimidine-allowed the study of the effect of the functionalization of the pyrimidine ring by different halogen atoms bound to the same molecular site, or by the same halogen atom bound to different molecular sites. The theoretical investigation of the inductive and resonance effects in the C(1s) ionization confirms the soundness of the resonance model for a qualitative description of the properties of an aromatic system. Moreover, the combination of the experimental results and the theoretical analysis provides a detailed description of the effects of the halogen atom on the screening of a C(1s) hole in the aromatic pyrimidine ring.