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Fourth-generation storage rings enabled by multi-bend achromat lattices are being inaugurated worldwide and many more are planned for the next decade. These sources deliver stable ultra-high brightness radiation with unmatched levels of transverse coherence by virtue of their highly advanced magnetic lattices. Optimization of these challenging and strongly nonlinear lattices with many degrees of freedom bounded by extensive sets of constraints and multiple often conflicting optimization goals is highly demanding and requires application of the most advanced numerical tools available to the community. While multi-objective genetic algorithms have been very successful in supporting these optimization efforts, the algorithms suffer from a fundamental limitation of their stochastic nature: an exceedingly vast number of candidate lattices, most of which eventually are rejected, has to be fully evaluated. This comes at immense computational cost and thus drives excessive runtime despite use of large supercomputing clusters. We therefore propose to employ deep learning techniques and iterative retraining of neural networks to massively accelerate such lattice evaluation, thereby allowing lattice optimization to rely on far fewer a priori assumptions, open up to larger search ranges, and include right from the start and in parallel multiple error distributions to find truly global optima, all while completing a full optimization campaign in weeks rather than months. In this paper we present the neural network designs, the deep learning approach, iterative retraining procedures, and demonstrate how these machine learning techniques can be incorporated into existing state-of-the-art optimization workflows with only minimal changes applied to the optimization pipeline itself and none at all to the employed tracking codes.

Filomena Russo,1 Marco Galluzzo,2,3 Luca Stingeni,4 Severino Persechino,5 Leonardo Zichichi,6 Andrea Conti,7 Claudia Giofrè,8 Valentina Dini,9 Martina Vispi,10 Laura Atzori,11 Angelo Cattaneo,12 Aurora Parodi,13 Federico Bardazzi,14 Giuseppe Stinco,15 Paolo Dapavo,16 Giampiero Girolomoni,17 Maria Letizia Musumeci,18 Manuela Papini,19 Marina Venturini,20 Stefano Dastoli,21 Sergio Di Nuzzo,22 Maria Concetta Fargnoli,23 Gianluca Pagnanelli,24 Nicoletta Bernardini,25 Daniele Mario Gambini,26 Piergiorgio Malagoli,27 Carlo Mazzatenta,28 Ketty Peris,29 Iris Zalaudek,30 Gabriella Fabbrocini31 ,† Francesco Loconsole,32 Camilla Vassallo,33 Lucia Pietroleonardo,34 Francesca Prignano,35 Chiara Franchi,36 Anna Maria Offidani,37 Claudio Bonifati,38 Vito Di Lernia,39 Giovanni Gigante,40 Marta Silvia Bartezaghi,40 Matteo Franchi,41,42 Paola Ursoleo,40 Elisabetta Aloisi40 1Dermatology Section, Department of Medical, Surgical and Neurological Science, University of Siena, S. Maria Alle Scotte Hospital, Siena, Italy; 2Department of Systems Medicine, University of Rome “Tor Vergata”, Rome, Italy; 3Dermatology Unit, Fondazione Policlinico “Tor Vergata”, Rome, Italy; 4Section of Dermatology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy; 5Dermatology Unit, NESMOS Department, Faculty of Medicine & Psychology, Sapienza University of Rome, Sant’Andrea University Hospital, Rome, Italy; 6Unit of Dermatology, San Antonio Abate Hospital, Trapani, Italy; 7Section of Dermatology, Department of Specialized Medicine, University of Modena and Reggio Emilia, Modena, Italy; 8U.O.C. Dermatologia, A.O. Papardo, Messina, Italy; 9Section of Dermatology, Department of Medicine and Oncology, University of Pisa, Pisa, Italy; 10Dermatology Unit, Misericordia Hospital, Grosseto, Italy; 11Dermatology Unit, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy; 12Dermatology Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milano, Italy; 13Section of Dermatology, DiSSal University of Genoa, Ospedale-Policlinico San Martino IRCCS, Genova, Italy; 14Dermatology Division, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy; 15Section of Dermatology, Department of Medicine, University of Udine, Udine, Italy; 16Section of Dermatology, Department of Medical Sciences, University of Turin, Turin, Italy; 17Section of Dermatology, Department of Medicine, University of Verona, Verona, Italy; 18Section of Dermatology, Department of Medical and Surgical Specialties, University of Catania, Catania, Italy; 19Dermatology Clinic of Terni, University of Perugia, Perugia, Italy; 20Section of Dermatology, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; 21Department of Health Sciences, Magna Graecia University, Catanzaro, Italy; 22Department of Medicine and Surgery, University of Parma, Parma, Italy; 23Section of Dermatology, Department of Biotechnological and Applied Clinical Science, University of L’Aquila, L’Aquila, Italy; 24Department of Dermatology, Istituto Dermopatico dell’Immacolata - IRCCS, Roma, Italy; 25Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Dermatology Unit, “Daniele Innocenzi”, Asl Latina, Italy; 26Dermatology Unit, ASST Papa Giovanni XXIII Hospital, Bergamo, Italy; 27Dermatology Unit, Azienda Ospedaliera San Donato Milanese, Milan, Italy; 28Dermatology Unit, Lucca Azienda USL Toscana Nord Ovest, Pisa, Italy; 29Department of Translational Medicine and Surgery, IRCCS A. Gemelli University Polyclinic Foundation, Sacred Heart Catholic University, Rome, Italy; 30Department of Dermatology, University of Trieste, Trieste, Italy; 31Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy; 32Department of Dermatology, University of Bari, Bari, Italy; 33Institute of Dermatology, IRCCS Policlinico San Matteo Foundation and University of Pavia, Pavia, Italy; 34Dermatology Unit, Vito Fazzi Hospital, Lecce, Italy; 35Dermatology Clinic, Department of Health Sciences, University of Florence, Florence, Italy; 36Dermatology Unit, IRCCS IO Galeazzi, Milan, Italy; 37Dermatological Clinic, Polytechnic University of the Marche Region, Ancona, Italy; 38Department of Dermatology, Istituto Dermatologico San Gallicano - IRCCS, Roma, Italy; 39Dermatology Unit, Arcispedale S. Maria Nuova IRCCS, Reggio Emilia, Italy; 40Novartis Farma SpA, Origgio, Italy; 41National Centre for Healthcare Research and Pharmacoepidemiology, Milan, Italy; 42Laboratory of Healthcare Research and Pharmacoepidemiology, Department of Statistics and Quantitative Methods, University of Milano Bicocca, Milan, Italy†Gabriella Fabbrocini passed away on 3 March 2023Correspondence: Filomena Russo, Dermatology Section, Department of Medical, Surgical and Neurological Science, University of Siena, S. Maria Alle Scotte Hospital, Siena, Italy, Email file.russo@libero.itPurpose: SUPREME, a phase IIIb study conducted in Italy, demonstrated safety and high efficacy of secukinumab for up to 72 weeks in patients with moderate-to-severe plaque-type psoriasis. SUPREME 2.0 study aimed to provide real-world data on the long-term drug survival and effectiveness of secukinumab beyond 72 weeks.Patients and Methods: SUPREME 2.0 is a retrospective observational chart review study conducted in patients previously enrolled in SUPREME study. After the end of the SUPREME study, eligible patients continued treatment as per clinical practice, and their effectiveness and drug survival data were retrieved from medical charts.Results: Of the 415 patients enrolled in the SUPREME study, 297 were included in SUPREME 2.0; of which, 210 (70.7%) continued secukinumab treatment throughout the 42-month observation period. Patients in the biologic-naïve cohort had higher drug survival than those in the biologic-experienced cohort (74.9% vs 61.7%), while HLA-Cw6–positive and HLA-Cw6–negative patients showed similar drug survival (69.3% and 71.9%). After 42 months, Psoriasis Area and Severity Index (PASI) 90 was achieved by 79.6% of patients overall; with a similar proportion of biologic-naïve and biologic-experienced patients achieving PASI90 (79.8% and 79.1%). The mean absolute PASI score reduced from 21.94 to 1.38 in the overall population, 21.90 to 1.24 in biologic-naïve and 22.03 to 1.77 in biologic-experienced patients after 42 months. The decrease in the absolute PASI score was comparable between HLA-Cw6–positive and HLA–Cw6-negative patients. The baseline Dermatology Life Quality Index scores also decreased in the overall patients (10.5 to 2.32) and across all study sub-groups after 42 months. Safety was consistent with the known profile of secukinumab, with no new findings.Conclusion: In this real-world cohort study, secukinumab showed consistently high long-term drug survival and effectiveness with a favourable safety profile.Keywords: psoriasis, secukinumab, real-world evidence, drug survival, SUPREME

We examine the effect of higher-harmonic passive cavities (HHCs) on the beam response to rf noise. Upon invoking certain assumptions to make the problem tractable, we employ Vlasov methods to show that when the dipole approximation applies the HHCs have a generally limited impact. Beam loading in the main cavity is included in the analysis. We illustrate our results and the limitations of our model in application to the Lawrence Berkeley National Laboratory ALS (Advanced Light Source) and the future ALS Upgrade (ALS-U) offering validation against macroparticle simulations.

The Advanced Light Source Upgrade will implement on axis single-train swap-out injection employing an accumulator between the booster and storage rings. The accumulator ring (AR) design is a twelve period triple-bend achromat that will be installed along the inner circumference of the storage-ring tunnel. A nonconventional injection scheme will be utilized for top-off off axis injection from the booster into the AR meant to accommodate a large ∼300 nm emittance beam into a vacuum-chamber with a limiting horizontal aperture radius as small as 8 mm. The scheme incorporates three dipole kickers distributed over three sectors, with two kickers perturbing the stored beam and the third affecting both the stored and the injected beam trajectories. This paper describes this "3DK"injection scheme and how it fits the AR's particular requirements. We describe the design and optimization process, and how we evaluated its fitness as a solution for booster-to-accumulator ring injection.

The ALS-U light source will implement on-axis single-train swap-out injectionemploying an accumulator between the booster and storage rings. The accumulatorring design is a twelve period triple-bend achromat that will be installedalong the inner circumference of the storage-ring tunnel. A non-conventionalinjection scheme will be utilized for top-off off-axis injection from thebooster into the accumulator ring meant to accommodate a large $\sim 300$~nmemittance beam into a vacuum-chamber with a limiting horizontal aperture radiusas small as $8$ mm. The scheme incorporates three dipole kickers distributedover three sectors, with two kickers perturbing the stored beam and the thirdaffecting both the stored and the injected beam trajectories. This paperdescribes this ``3DK'' injection scheme and how it fits the accumulator ring'sparticular requirements. We describe the design and optimization process, andhow we evaluated its fitness as a solution for booster-to-accumulator ringinjection.

We study the effect of a passive harmonic cavity, introduced to cause bunch lengthening, in an electron storage ring. We derive a formula for the induced voltage from such a cavity with high Q, excited by a sequence of bunches, allowing for arbitrary gaps in the sequence and arbitrary currents. Except for a minor term that can be determined iteratively, the voltage is given in terms of a single mode of the Fourier transforms of the bunch forms, namely, the mode at the resonant frequency of the cavity. Supposing that the only wakefield is from the harmonic cavity, we derive a system of coupled Haïssinski equations which determine the bunch positions and profiles in the equilibrium state. The number of unknowns in the system is only twice the number of bunches, and it can be solved quickly by a Newton iteration, starting with a guess determined by path following from a solution at a weak current. We explore the effect of the fill pattern on the bunch lengthening and also the dependence on the shunt impedance and detuning of the cavity away from the third harmonic of the main accelerating cavity. We consider two measures to reduce the effects of gaps: (i) distribution of the gaps around the ring to the greatest extent allowed and (ii) "guard bunches"with higher charges adjacent to the gaps, compensating for the charge missing in gaps. Results for parameters of the forthcoming Advanced Light Source upgrade are presented.

The concept of using a single nonlinear kicker (NLK) to inject electron beams into a storage ring has been proposed and tested in several synchrotron radiation light source facilities. Different from pulsed dipole kicker magnets used in a conventional local-bump injection, the single nonlinear kicker provides a nonlinear distribution of magnetic fields which has a maximum value off axis where the injected beam arrives and a zero or near-zero value at the center where the stored beam passes by. Therefore, the injected beam will receive a kick from the NLK and lose its transverse momentum, and will be eventually captured by the storage ring. In the meantime the stored beam at the center will receive no kick or less kick, which significantly reduces the injection perturbations on the stored beam. In addition, the NLK injection requires less space for the kicker and removes the complications of synchronizing four pulsed kicker magnets. Because of these advantages, several light source facilities are either proposing or already using this NLK injection as a replacement of the conventional local-bump injection scheme. In this paper, we will discuss the working principal of this NLK injection, and use both Advanced Light Source and Advanced Light source Upgrade as examples to optimize the NLK injections. By optimizing the NLK design and injection conditions, we could achieve maximum injection efficiencies for both facilities with a large injected beam from the existing ALS booster.

We present a new accelerator toolbox (AT)-based toolkit for simulating the commissioning of light-source storage rings. The toolkit provides a framework for supporting high-level scripts to represent with realism the various procedures (e.g., orbit and optics correction, beam-based alignment, etc.) encountered during commissioning and is designed to mirror as closely as possible the reality as seen from the control room. Emphasis is placed on the inclusion of a comprehensive set of error sources and faithful modeling of beam diagnostics. The toolkit capabilities are demonstrated in an application to the recent design and commissioning studies of the Advanced Light Source Upgrade (ALS-U) Accumulator Ring, a short-time successful commissioning of which will be critical to the overall ALS-U project success.

We introduce a perturbation-theory, mode-analysis method for longitudinal multibunch instabilities driven by the higher harmonic cavity (HHC) fundamental mode. The method, based on the exact solution of the unperturbed particle motion in the rf bucket and suitable for modeling the effect of cavities with general settings, is applied to study the feasibility of reutilizing the existing Advanced Light Source (ALS) HHCs in the ALS Upgrade (ALS-U). We find that with ALS cavities the ALS-U would be susceptible to a fast =1 mode instability. Interestingly, the instability is driven by the imaginary rather than the real part of the cavity fundamental-mode impedance.

The ALS upgrade into a diffraction-limited soft x-rays light source requires a small emittance, which is achieved by much stronger focusing than in the present ALS. Very strong focusing elements and a relatively small vacuum chamber make the required rapid commissioning a significant challenge. This paper will describe the progress towards a start-to-end simulation of the machine commissioning and present first simulation results.

The effect of rf harmonic cavities on the transverse mode-coupling instability (TMCI) is still not very well understood. We offer a fresh perspective on the problem by proposing a new numerical method for mode analysis and investigating a regime of potential interest to the new generation of light sources where resistive wall is the dominant source of transverse impedance. When the harmonic cavities are tuned for maximum flattening of the bunch profile we demonstrate that at vanishing chromaticities the transverse single-bunch motion is unstable at any current, with growth rate that in the relevant range scales as the 6th power of the current. With these assumptions and radiation damping included, we find that for machine parameters typical of 4th-generation light sources the presence of harmonic cavities could reduce the instability current threshold by more than a factor two.

The ALS-U upgrade promises to deliver diffraction limited performance throughout the soft x-ray range by lowering the horizontal emittance to about 50 pm resulting in 2-3 orders of brightness increase for soft x-rays compared to the current ALS. The design utilizes a multi bend achromat lattice with on-axis swap-out injection and an accumulator ring. One central design goal is to install and commission ALS-U within a short dark period. This paper summarizes the status of the conceptual design of the accelerator, as well as some results of the R&D program that has been ongoing for the last 3 years.

The shot-noise driven microbunching instability can significantly degrade electron beam quality in x-ray free electron laser light sources. Experiments were carried out at the Linac Coherent Light Source (LCLS) to study this instability. In this paper, we present start-to-end simulations of the shot-noise driven microbunching instability experiment at the LCLS using the real number of electrons. The simulation results reproduce the measurements quite well. A microbunching self-heating mechanism is also illustrated in the simulation, which helps explain the experimental observation.

Background: Early melanoma detection is the main factor affecting prognosis and survival. For that reason, non‐invasive technologies have been developed to provide a more accurate diagnosis. Recently, line‐field confocal optical coherence tomography (LC‐OCT) was developed to provide an in vivo, imaging device, with deep penetration and cellular resolution in three dimensions. Combining the advantages of conventional OCT and reflectance confocal microscopy, this tool seems to be particularly suitable for melanocytic lesions. Objectives: The objective of this study was to identify and describe the correlation between specific dermoscopic criteria and LC‐OCT features in three dimensions associated with melanocytic lesions. Methods: Dermoscopic and LC‐OCT images of 126 melanocytic lesions were acquired in three different centres. The following dermoscopic criteria have been considered: reticular pattern, dots and globules, structureless areas, blue‐whitish veil, regression structures, negative network, homogeneous pattern, streaks and blotches. Results: 69 (55%) benign and 57 (45%) malignant lesions were analysed. A regular reticular pattern was found associated in the 75% of the cases with the presence of elongated rete ridges with pigmented cells along the basal layer, while atypical reticular pattern showed an irregular organization of rete ridges with melanocytic hyperplasia, broadened and fused ridges and elongated nests. Both typical and atypical dots and globules were found associated with melanocytic nests in the dermis or at the dermoepidermal junction (DEJ), as well as with keratin cysts/pseudocysts. Grey globules corresponded to the presence of melanin‐containing dermal inflammatory cells (melanophages) within the papillae. Structureless brown/black areas correlated with alterations of the DEJ. We observed the same DEJ alterations, but with the presence of dermal melanophages, in 36% of the cases of blue/white/grey structureless areas. A description of each LC‐OCT/dermoscopy correlation was made. Conclusions: LC‐OCT permitted for the first time to perform an in vivo, 3D correlation between dermoscopic criteria and pathological‐like features of melanocytic lesions. [ABSTRACT FROM AUTHOR]

The need to operate an rf-gun-based electron photoinjector with a beam emitted away from the cathode center can occur under various circumstances. First, in some cases the cathode can be affected by ion back-bombardment that progressively reduces the quantum efficiency (QE) in its center, making off-axis operation mandatory; second, in some cases the drive laser intensity can be sufficiently high to generate QE depletion in the cathode area illuminated by the laser, forcing off-axis operation; last, in cathodes with nonuniform QE distribution it could be convenient to operate off axis to exploit a better QE. However, operation in this mode may lead to growth of the projected transverse beam emittances due to correlations between the transverse and longitudinal degrees of freedom that are introduced within the gun and downstream rf cavities. A strategy is described to mitigate this emittance growth by allowing the beam to propagate along a carefully tuned off-axis trajectory in downstream rf cavities to remove the time-dependent rf kicks introduced in the gun. Along this trajectory, short range wakefields do not degrade the emittance, and long range wakefields degrade the emittance for very high repetition rate only.

The buildup of low energy electrons in an accelerator, known as electron cloud, can be severely detrimental to machine performance. Under certain beam conditions, the beam can become resonant with the cloud dynamics, accelerating the buildup of electrons. This paper will examine two such effects: multipacting resonances, in which the cloud development time is resonant with the bunch spacing, and cyclotron resonances, in which the cyclotron period of electrons in a magnetic field is a multiple of bunch spacing. Both resonances have been studied directly in dipole fields using retarding field analyzers installed in the Cornell Electron Storage Ring. These measurements are supported by both analytical models and computer simulations.

Using a 1D steady-state free-space coherent synchrotron radiation (CSR) model, we identify a special design setting for a triple-bend isochronous achromat that yields vanishing emittance growth from CSR. When a more refined CSR model with transient effects is included in the analysis, numerical simulations show that the main effect of the transients is to shift the emittance growth minimum slightly, with the minimum changing only modestly.

Improvements in brightness and coherent flux of about two orders of magnitude over operational storage ring based light sources are possible using multi bend achromat lattice designs [1]. These improvements can be implemented as upgrades of existing facilities, like the proposed upgrade of the Advanced Light Source, making use of the existing infrastructure, thereby reducing cost and time needed to reach full scientific productivity on a large number of beamlines. An R&D program was started at LBNL to further develop the technologies necessary for diffraction-limited storage rings. It involves many areas, and focuses on the specific needs of soft x-ray facilities [2]: NEG coating of small chambers, swap-out injection, bunch lengthening, magnets/radiation production, x-ray optics, and beam physics design optimization. Hardware prototypes have been built and concepts and equipment was tested in beam tests on the existing ALS.

The popularity of tattoos has led to an increase in associated skin reactions, including complications such as infection, allergic reactions and rare conditions such as tattoo‐induced cutaneous lymphoid hyperplasia (CLH). CLH is a benign lymphoproliferative reaction with clinical features resembling malignant cutaneous lymphomas. Non‐invasive diagnostic tools like reflectance confocal microscopy (RCM) and the new line‐field confocal optical coherence tomography (LC‐OCT) are being studied in dermatology better to understand the morphological patterns of many dermatological diseases. Between September 2021 and May 2023, patients with suspicious lesions for tattoo‐related CLH were analysed using RCM and LC‐OCT before confirming the diagnosis of CLH through skin biopsy and histopathological examination. The study included five cases of CLH. It focused on the analysis of high‐quality LC‐OCT images/videos and RCM images to investigate the features of CLH in tattooed individuals. Most (80%) cases exhibited a mixed T and B lymphocyte infiltration subtype, while 20% showed a predominant T infiltration subtype. RCM and LC‐OCT revealed characteristic features, including architectural disarray, fibrosis, lymphoid infiltrates, and pigment deposits in the epidermis and dermis. Non‐invasive tools such as RCM and LC‐OCT are valuable in diagnosing tattoo‐related CLH. While skin biopsy remains the current standard for diagnosis, RCM and LC‐OCT can serve as helpful adjuncts in identifying the most representative area for biopsy. They may potentially become alternative diagnostic options in the future, offering benefits in terms of cost, diagnostic efficiency, aesthetics and patient satisfaction as the prevalence of tattoo‐related adverse reactions continues to rise. [ABSTRACT FROM AUTHOR]