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We present an optical/near-IR survey of 11 variable young stars (EXors and EXor candidates) aimed at deriving and monitoring their accretion properties. About 30 optical and near-infrared spectra ( R∼1500–2000 ) were collected between 2014 and 2019 with the Large Binocular Telescope (LBT). From the spectral analysis we have derived the accretion luminosity (L acc ) and mass accretion rate ( Ṁacc ), the visual extinction (A V), the temperature and density of the permitted line formation region (T, n H), and the signature of the outflowing matter. Two sources (ASASSN-13db and iPTF15afq) have been observed in outburst and quiescence, three during a high level of brightness (XZ Tau, PV Cep, and NY Ori), and the others in quiescence. These latter have L acc and Ṁacc in line with the values measured in classical T Tauri stars of similar mass. All sources observed more than once present L acc and Ṁacc variability. The most extreme case is ASASSN-13db, for which Ṁacc decreases by two orders of magnitude from the outburst peak in 2015 to quiescence in 2017. Also, in NY Ori L acc decreases by a factor 25 in one year. In 80% of the sample we detect the [O i] 6300 Å line, a tracer of mass loss. From the variability of the Hα/[O i] 6300 Å ratio, we conclude that mass accretion variations are larger than mass loss variations. From the analysis of the H i recombination lines, a correlation is suggested between the density of the line formation region, and the level of accretion activity of the source.

This paper summarizes the discussion at the Approximation Methods Panel that was held at the 9thAIAA/ISSMO Symposium on Multidisciplinary Analysis & Optimization in Atlanta, GA on September 2–4, 2002. The objective of the panel was to discuss the current state-of-the-art of approximation methods and identify future research directions important to the community. The panel consisted of five representatives from industry and government: (1) Andrew J. Booker from The Boeing Company, (2) Dipankar Ghosh from Vanderplaats Research & Development, (3) Anthony A. Giunta from Sandia National Laboratories, (4) Patrick N. Koch from Engineous Software, Inc., and (5) Ren-Jye Yang from Ford Motor Company. Each panelist was asked to (i) give one or two brief examples of typical uses of approximation methods by his company, (ii) describe the current state-of-the-art of these methods used by his company, (iii) describe the current challenges in the use and adoption of approximation methods within his company, and (iv) identify future research directions in approximation methods. Several common themes arose from the discussion, including differentiating between design of experiments and design and analysis of computer experiments, visualizing experimental results and data from approximation models, capturing uncertainty with approximation methods, and handling problems with large numbers of variables. These are discussed in turn along with the future directions identified by the panelists, which emphasized educating engineers in using approximation methods.

During the eruption of Eyjafjallajökull in April–May 2010 multi-wavelength Raman lidar measurements were performed at the CNR-IMAA Atmospheric Observatory (CIAO), whenever weather conditions permitted observations. A methodology both for volcanic layer identification and accurate aerosol typing has been developed. This methodology relies on the multi-wavelength Raman lidar measurements and the support of long-term lidar measurements performed at CIAO since 2000. The aerosol mask for lidar measurements performed at CIAO during the 2010 Eyjafjallajökull eruption has been obtained. Volcanic aerosol layers were observed in different periods: 19–22 April, 27–29 April, 8–9 May, 13–14 May and 18–19 May. A maximum aerosol optical depth of about 0.12–0.13 was observed on 20 April, 22:00 UTC and 13 May, 20:30 UTC. Volcanic particles were detected at low altitudes, in the free troposphere and in the upper troposphere. Occurrences of volcanic particles within the PBL were detected on 21–22 April and 13 May. A Saharan dust event was observed on 13–14 May: dust and volcanic particles were simultaneously detected at CIAO at separated different altitudes as well as mixed within the same layer. Lidar ratios at 355 and 532 nm, the Ångström exponent at 355/532 nm, the backscatter-related Ångström exponent at 532/1064 nm and the particle linear depolarization ratio at 532 nm measured inside the detected volcanic layers are discussed. The dependence of these quantities on relative humidity has been investigated by using co-located microwave profiler measurements. The measured values of these intensive parameters indicate the presence of volcanic sulfates/continental mixed aerosol in the volcanic aerosol layers observed at CIAO. In correspondence of the maxima observed in the volcanic aerosol load on 19–20 April and 13 May, different values of intensive parameters were observed. Apart from the occurrence of sulfate aerosol, these values indicate also the presence of some ash which is affected by the aging during transport over Europe.

Background:Risankizumab is the most recently approved drug used for the treatment of Psoriatic arthritis (PsA). Risankizumab is a humanized IgG1 monoclonal antibody that specifically inhibits interleukin 23 (IL-23) by binding to its p19 subunit.Objectives:The KEEPsAKE 1 and 2 trials have demonstrated the efficacy and safety of Risankizumab in naïve and TNF-experienced patients with PsA. Here we report the real-life efficacy and safety of Risankizumab in an Italian cohort of PsA patients.Methods:In this observational retrospective trial, we reported clinical data of PsA patients who satisfied CASPAR criteria admitted to the combined dermatologist-rheumatologist outpatient clinics of 5 Italian centers. Each patient underwent a complete clinical exam evaluating cutaneous and joint disease with activity index. We used DAPSA and VAS pain to assess the clinical activity of joint disease and BSA, PASI and VAS pruritus as dermatological indexes. All patients were treated with Risankizumab according to common clinical practice. The primary endpoint was the achievement of low disease activity or remission according to DAPSA after 6 months of therapy with good efficacy also on the skin component.Results:In this work, we enrolled 44 PsA patients (28 males and 16 females) who satisfied CASPAR criteria. The mean age was 56.2 years and most of the patients were overweight (mean BMI 29.1). Most of them had a long disease duration (mean duration 11.4 years) so it is not surprising that 73% of patients were already bDMARDs experienced (of them 61% TNF non-responders). At baseline, all patients reported moderate disease activity (mean DAPSA 19.7) with extensive skin psoriasis (mean Body surface area 21.3% and mean PASI 16.3). After 6 months of treatment with Risankizumab, 62% of patients obtained a good DAPSA response (p<0.0001). Figure 1 Of them 19% reached remission and 43% reached low disease activity. Moreover, good clinical responses were observed also for BSA and PASI with a reduction respectively of 75% and 87%. After 12 months of treatment, 82% of patients were in low disease activity or remission with a mean DAPSA of 7.4 (p<0.0001). Figure 2Conclusion:This is the first paper that evaluated the efficacy of Risankizumab in PsA patients in a real-life setting. Patients enrolled in clinical trials do not represent patients who are evaluated in a clinical setting and who have multiple comorbidities that influence therapeutic choice and pharmacological response. Particularly, our PsA patients had a long disease duration and most of them were bDMARDs experienced. Risankizumab was demonstrated to be efficacious both in naïve and in multi-failure patients. The primary and secondary endpoints were reached: 62% of patients had a good clinical response at 6 months and 82% of patients were in LDA/remission at 12 months of treatment. Numerous clinical trials and real-life data showed the effectiveness of Risankizumab on psoriasis, confirming the pivotal role of blocking IL-23 on the skin. The effectiveness on skin psoriasis was also confirmed in our work: after 6 months of treatment, a reduction in PASI of approximately 90% was recorded (mean PASI 2). During the entire follow-up period, no patient reported a reaction at the injection site, infectious episodes, or any adverse event worthy of medical discussion. In conclusion, risankizumab is a good option also for PsA patients who are multi-drug resistant. Further studies are necessary to confirm our results and to confirm the efficacy of risankizumab in “complex” patients in real life.REFERENCES:[1] Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial. Kristensen LE, Keiserman M, Papp K, McCasland L, White D, Lu W, Wang Z, Soliman AM, Eldred A, Barcomb L, Behrens F. Ann Rheum Dis. 2022 Feb;81(2):225-231.[2] Efficacy and safety of risankizumab for active psoriatic arthritis: 52-week results from the KEEPsAKE 2 study.Östör A, Van den Bosch F, Papp K, Asnal C, Blanco R, Aelion J, Lu W, Wang Z, Soliman AM, Eldred A, Padilla B, Kivitz A.Rheumatology (Oxford). 2023 Jun 1;62(6):2122-2129.Acknowledgements:NIL.Disclosure of Interests:None declared.

Despite the relevant research efforts, the causes of amyotrophic lateral sclerosis (ALS) are still unknown and no effective cure is available. Many authors suggest that ALS is a multi-system disease caused by a network failure instead of a cell-autonomous pathology restricted to motoneurons. Although motoneuronal loss is the critical hallmark of ALS given their specific vulnerability, other cell populations, including muscle and glial cells, are involved in disease onset and progression, but unraveling their specific role and crosstalk requires further investigation. In particular, little is known about the plastic changes of the degenerating motor system. These spontaneous compensatory processes are unable to halt the disease progression, but their elucidation and possible use as a therapeutic target represents an important aim of ALS research. Genetic animal models of disease represent useful tools to validate proven hypotheses or to test potential therapies, and the conception of novel hypotheses about ALS causes or the study of pathogenic mechanisms may be advantaged by the use of relatively simple in vivo models recapitulating specific aspects of the disease, thus avoiding the inclusion of too many confounding factors in an experimental setting. Here, we used a neurotoxic model of spinal motoneuron depletion induced by injection of cholera toxin-B saporin in the gastrocnemius muscle to investigate the possible occurrence of compensatory changes in both the muscle and spinal cord. The results showed that, following the lesion, the skeletal muscle became atrophic and displayed electromyographic activity similar to that observed in ALS patients. Moreover, the changes in muscle fiber morphology were different from that observed in ALS models, thus suggesting that some muscular effects of disease may be primary effects instead of being simply caused by denervation. Notably, we found plastic changes in the surviving motoneurons that can produce a functional restoration probably similar to the compensatory changes occurring in disease. These changes could be at least partially driven by glutamatergic signaling, and astrocytes contacting the surviving motoneurons may support this process.

Sonic hedgehog (Shh) signaling is a key pathway within the central nervous system (CNS), during both development and adulthood, and its activation via the 7-transmembrane protein Smoothened (Smo) may promote neuroprotection and restoration during neurodegenerative disorders. Shh signaling may also be activated by selected glucocorticoids such as clobetasol, fluocinonide and fluticasone, which therefore act as Smo agonists and hold potential utility for regenerative medicine. However, despite its potential role in neurodegenerative diseases, the impact of Smo-modulation induced by these glucocorticoids on adult neural stem cells (NSCs) and the underlying signaling mechanisms are not yet fully elucidated. The aim of the present study was to evaluate the effects of Smo agonists (i.e., purmorphamine) and antagonists (i.e., cyclopamine) as well as of glucocorticoids (i.e., clobetasol, fluocinonide and fluticasone) on NSCs in terms of proliferation and clonal expansion. Purmorphamine treatment significantly increased NSC proliferation and clonal expansion via GLI-Kruppel family member 1 (Gli1) nuclear translocation and such effects were prevented by cyclopamine co-treatment. Clobetasol treatment exhibited an equivalent pharmacological effect. Moreover, cellular thermal shift assay suggested that clobetasol induces the canonical Smo-dependent activation of Shh signaling, as confirmed by Gli1 nuclear translocation and also by cyclopamine co-treatment, which abolished these effects. Finally, fluocinonide and fluticasone as well as control glucocorticoids (i.e., prednisone, corticosterone and dexamethasone) showed no significant effects on NSCs proliferation and clonal expansion. In conclusion, our data suggest that Shh may represent a druggable target system to drive neuroprotection and promote restorative therapies.

Direct remote-sensing observations of the solar poles have been hindered by the restricted view obtained from the ecliptic plane. For the first time ever, Solar Orbiter with its remote-sensing instruments observed the poles of the Sun from out of the ecliptic in the spring of 2025. Here, we report the first measurements of the magnetic field of the solar poles taken when Solar Orbiter was at heliographic latitudes ranging between 14 .° 9 and 16 .° 7. The data sets were collected by the High Resolution Telescope of the Polarimetric and Helioseismic Imager on board Solar Orbiter (SO/PHI-HRT). Two sets of observations, approximately one month apart, for the south and north pole are considered in this work. The magnetic flux and flux density measured during these campaigns are reported as a function of the heliographic latitude observed by SO/PHI-HRT. The net fluxes show a different latitudinal distribution for the two polar caps. We also discuss the observed dependence of the measured fluxes on the viewing angle. These first results highlight the importance of high-resolution direct measurements of the polar field, paving the way for the high-latitude observations planned for SO/PHI-HRT in the coming years.

We report the results of a multi-instrument, multi-technique, coordinated study of the solar eruptive event of 13 May 2005. We discuss the resultant Earth-directed (halo) coronal mass ejection (CME), and the effects on the terrestrial space environment and upper Earth atmosphere. The interplanetary CME (ICME) impacted the Earth’s magnetosphere and caused the most-intense geomagnetic storm of 2005 with a Disturbed Storm Time ( Dst ) index reaching −263 nT at its peak. The terrestrial environment responded to the storm on a global scale. We have combined observations and measurements from coronal and interplanetary remote-sensing instruments, interplanetary and near-Earth in-situ measurements, remote-sensing observations and in-situ measurements of the terrestrial magnetosphere and ionosphere, along with coronal and heliospheric modelling. These analyses are used to trace the origin, development, propagation, terrestrial impact, and subsequent consequences of this event to obtain the most comprehensive view of a geo-effective solar eruption to date. This particular event is also part of a NASA-sponsored Living With a Star (LWS) study and an on-going US NSF-sponsored Solar, Heliospheric, and INterplanetary Environment (SHINE) community investigation.

Long-term observations of aerosol and clouds are of crucial importance to understand the weather climate system. At the Istituto di Metodologie per l'Analisi Ambientale of the Italian National Research Council (CNR-IMAA) an advanced atmospheric observatory, named CIAO, is operative. CIAO (CNR-IMAA Atmospheric Observatory) main scientific objective is the long term measurement for the climatology of aerosol and cloud properties. Its equipment addresses the state-of-the-art for the ground-based remote sensing of aerosol, water vapour and clouds including active and passive sensors, like lidars, ceilometers, radiometers, and a radar. This paper describes the CIAO infrastructure, its scientific activities as well as the observation strategy. The observation strategy is mainly organized in order to provide quality assured measurements for satellite validation and model evaluation and to fully exploit the synergy and integration of the active and passive sensors for the improvement of atmospheric profiling. Data quality is ensured both by the application of protocols and dedicated quality assurance programs mainly related to the projects and networks in which the infrastructure is involved. The paper also introduces examples of observations performed at CIAO and of the synergies and integration algorithms (using Raman lidar and microwave profiler data) developed and implemented at the observatory for the optimization and improvement of water vapour profiling. CIAO database represents an optimal basis to study the synergy between different sensors and to investigate aerosol-clouds interactions, and can give a significant contribution to the validation programs of the incoming new generation satellite missions.

Rheumatological systemic autoimmune diseases, such as connective tissue diseases, rheumatoid arthritis or spondyloarthritis, are characterized by the presence of joint involvement associated with extra-articular manifestations. Among them, cutaneous diseases are often the most relevant and representative clinical manifestation, as in psoriatic arthritis, scleroderma or systemic lupus erythematosus. In this context, it is useful for rheumatologists to understand better skin diseases and their histopathological features. Evaluation of skin biopsy specimens can be helpful not only to confirm the diagnosis in both classic and clinically atypical variants, but also to improve further our knowledge of the pathogenetic mechanisms and the close link between skin and articular diseases. In this review, we discuss the clinical features, diagnostic evaluation and the histopathological features of skin manifestation of the most relevant rheumatological autoimmune diseases.