Galaxy Formation and Symbiotic Evolution with the Inter-Galactic Medium in the Age of ELT-ANDES

High-resolution absorption spectroscopy toward bright background sources has had a paramount role in understanding early galaxy formation, the evolution of the intergalactic medium and the reionisation of the Universe. However, these studies are now approaching the boundaries of what can be achieved at ground-based 8-10m class telescopes. The identification of primeval systems at the highest redshifts, within the reionisation epoch and even into the dark ages, and of the products of the first generation of stars and the chemical enrichment of the early Universe, requires observing very faint targets with a signal-to-noise ratio high enough to detect very faint spectral signatures. In this paper, we describe the giant leap forward that will be enabled by ANDES, the high-resolution spectrograph for the ELT, in these key science fields, together with a brief, non-exhaustive overview of other extragalactic research topics that will be pursued by this instrument, and its synergistic use with other facilities that will become available in the early 2030s.Comment: 40 pages, 7 figures; submitted to Experimental Astronomy on behalf of the ANDES Science Tea

Leptomeningeal enhancement in multiple sclerosis: a focus on patients treated with hematopoietic stem cell transplantation

BackgroundLeptomeningeal enhancement (LME) is considered an MRI marker of leptomeningeal inflammation in inflammatory neurological disorders, including multiple sclerosis (MS). To our knowledge, no disease-modifying therapies (DMTs) have been demonstrated to affect LME number or morphology so far.MethodsMonocentric study investigating the frequency and number of LME in a cohort of people with (pw)MS who performed a 3 T brain MRI with a standardized protocol (including a post-contrast FLAIR sequence), and exploring the impact of autologous hematopoietic stem cell transplantation (AHSCT) on this marker. In a longitudinal pilot study, consecutive MRIs were also analyzed in a subgroup of pwMS, including patients evaluated both pre- and post-AHSCT.ResultsFifty-five pwMS were included: 24/55 (44%) had received AHSCT (AHSCT group) and 31 other treatments (CTRL group). At least one LME was identified in 19/55 (35%) cases (42 and 29% in the AHSCT and CTRL groups, respectively; p = 0.405). In the AHSCT group, LME number correlated with age at AHSCT (R = 0.50; p = 0.014), but not with age at post-treatment MRI. In the longitudinal pilot study (n = 8), one LME disappeared following AHSCT in 1/4 patients, whereas LME number was unchanged in the remaining four pwMS from the CTRL group.DiscussionThese results suggest that AHSCT may affect development and persistence of LME, strengthening the indication for early use of effective therapies bioavailable within the central nervous system (CNS), and therefore potentially targeting compartmentalized inflammation

Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease

BACKGROUND: Acute graft-versus-host disease (GVHD) remains a major limitation of allogeneic stem-cell transplantation; not all patients have a response to standard glucocorticoid treatment. In a phase 2 trial, ruxolitinib, a selective Janus kinase (JAK1 and JAK2) inhibitor, showed potential efficacy in patients with glucocorticoid-refractory acute GVHD. METHODS: We conducted a multicenter, randomized, open-label, phase 3 trial comparing the efficacy and safety of oral ruxolitinib (10 mg twice daily) with the investigator's choice of therapy from a list of nine commonly used options (control) in patients 12 years of age or older who had glucocorticoid-refractory acute GVHD after allogeneic stem-cell transplantation. The primary end point was overall response (complete response or partial response) at day 28. The key secondary end point was durable overall response at day 56. RESULTS: A total of 309 patients underwent randomization; 154 patients were assigned to the ruxolitinib group and 155 to the control group. Overall response at day 28 was higher in the ruxolitinib group than in the control group (62% [96 patients] vs. 39% [61]; odds ratio, 2.64; 95% confidence interval [CI], 1.65 to 4.22; P<0.001). Durable overall response at day 56 was higher in the ruxolitinib group than in the control group (40% [61 patients] vs. 22% [34]; odds ratio, 2.38; 95% CI, 1.43 to 3.94; P<0.001). The estimated cumulative incidence of loss of response at 6 months was 10% in the ruxolitinib group and 39% in the control group. The median failure-free survival was considerably longer with ruxolitinib than with control (5.0 months vs. 1.0 month; hazard ratio for relapse or progression of hematologic disease, non-relapse-related death, or addition of new systemic therapy for acute GVHD, 0.46; 95% CI, 0.35 to 0.60). The median overall survival was 11.1 months in the ruxolitinib group and 6.5 months in the control group (hazard ratio for death, 0.83; 95% CI, 0.60 to 1.15). The most common adverse events up to day 28 were thrombocytopenia (in 50 of 152 patients [33%] in the ruxolitinib group and 27 of 150 [18%] in the control group), anemia (in 46 [30%] and 42 [28%], respectively), and cytomegalovirus infection (in 39 [26%] and 31 [21%]). CONCLUSIONS: Ruxolitinib therapy led to significant improvements in efficacy outcomes, with a higher incidence of thrombocytopenia, the most frequent toxic effect, than that observed with control therapy

Autologous Hematopoietic Stem Cell Transplantation vs Intravenous Pulse Cyclophosphamide in Diffuse Cutaneous Systemic Sclerosis: A Randomized Clinical Trial

Importance: High-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation (HSCT) have shown efficacy in systemic sclerosis in phase 1 and small phase 2 trials. Objective: To compare efficacy and safety of HSCT vs 12 successive monthly intravenous pulses of cyclophosphamide. Design, Setting, and Participants: The Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial, a phase 3, multicenter, randomized (1:1), open-label, parallel-group, clinical trial conducted in 10 countries at 29 centers with access to a European Group for Blood and Marrow Transplantation–registered transplant facility. From March 2001 to October 2009, 156 patients with early diffuse cutaneous systemic sclerosis were recruited and followed up until October 31, 2013. Interventions: HSCT vs intravenous pulse cyclophosphamide. Main Outcomes and Measures: The primary end point was event-free survival, defined as time from randomization until the occurrence of death or persistent major organ failure. Results: A total of 156 patients were randomly assigned to receive HSCT (n = 79) or cyclophosphamide (n = 77). During a median follow-up of 5.8 years, 53 events occurred: 22 in the HSCT group (19 deaths and 3 irreversible organ failures) and 31 in the control group (23 deaths and 8 irreversible organ failures). During the first year, there were more events in the HSCT group (13 events [16.5%], including 8 treatment-related deaths) than in the control group (8 events [10.4%], with no treatment-related deaths). At 2 years, 14 events (17.7%) had occurred cumulatively in the HSCT group vs 14 events (18.2%) in the control group; at 4 years, 15 events (19%) had occurred cumulatively in the HSCT group vs 20 events (26%) in the control group. Time-varying hazard ratios (modeled with treatment × time interaction) for event-free survival were 0.35 (95% CI, 0.16-0.74) at 2 years and 0.34 (95% CI, 0.16-0.74) at 4 years. Conclusions and Relevance: Among patients with early diffuse cutaneous systemic sclerosis, HSCT was associated with increased treatment-related mortality in the first year after treatment. However, HCST conferred a significant long-term event-free survival benefit. Trial Registration: isrctn.org Identifier: ISRCTN5437125

Heavy element production in a compact object merger observed by JWST

The mergers of binary compact objects such as neutron stars and black holes are of central interest to several areas of astrophysics, including as the progenitors of gamma-ray bursts (GRBs) 1, sources of high-frequency gravitational waves (GWs) 2 and likely production sites for heavy-element nucleosynthesis by means of rapid neutron capture (the r-process) 3. Here we present observations of the exceptionally bright GRB 230307A. We show that GRB 230307A belongs to the class of long-duration GRBs associated with compact object mergers 4–6 and contains a kilonova similar to AT2017gfo, associated with the GW merger GW170817 (refs. 7–12). We obtained James Webb Space Telescope (JWST) mid-infrared imaging and spectroscopy 29 and 61 days after the burst. The spectroscopy shows an emission line at 2.15 microns, which we interpret as tellurium (atomic mass A = 130) and a very red source, emitting most of its light in the mid-infrared owing to the production of lanthanides. These observations demonstrate that nucleosynthesis in GRBs can create r-process elements across a broad atomic mass range and play a central role in heavy-element nucleosynthesis across the Universe

First stars signatures in high-z absorbers

International audienceThe first stars were likely more massive than those forming today and thus rapidly evolved, exploding as supernovae and enriching the surrounding gas with their chemical products. In the Local Group, the chemical signature of the first stars has been identified in the so-called Carbon-Enhanced Metal-Poor stars (CEMP-no). On the contrary, a similar C-excess was not found in dense neutral gas traced by high-redshift absorption systems. Here we discuss the recent discovery of three C-enhanced very metal-poor ([Fe/H] 50% of the metals in these absorber

First stars signatures in high-z absorbers

International audienceThe first stars were likely more massive than those forming today and thus rapidly evolved, exploding as supernovae and enriching the surrounding gas with their chemical products. In the Local Group, the chemical signature of the first stars has been identified in the so-called Carbon-Enhanced Metal-Poor stars (CEMP-no). On the contrary, a similar C-excess was not found in dense neutral gas traced by high-redshift absorption systems. Here we discuss the recent discovery of three C-enhanced very metal-poor ([Fe/H] 50% of the metals in these absorber

First stars signatures in high-z absorbers

The first stars were likely more massive than those forming today and thus rapidly evolved, exploding as supernovae and enriching the surrounding gas with their chemical products. In the Local Group, the chemical signature of the first stars has been identified in the so-called Carbon-Enhanced Metal-Poor stars (CEMP-no). On the contrary, a similar C-excess was not found in dense neutral gas traced by high-redshift absorption systems. Here we discuss the recent discovery of three C-enhanced very metal-poor ([Fe/H]< -2) optically thick absorbers at redshift z ~ 3-4, reported by (Saccardi et al. 2023). We show that these absorbers are extra-galactic tracers of the chemical signatures of the first stars, analogous to the CEMP-no stars observed in the Galactic halo and ultra-faint dwarf galaxies. Furthermore, by comparing observations with model predictions we demonstrate that these systems have most likely been imprinted by first stars exploding as low-energy supernovae, which provided > 50% of the metals in these absorbersComment: Mem. S.A.It. in pres

Il tirocinio in Servizio sociale durante la pandemia covid-19. Opportunità e limiti dell'esperienza toscana, nell'emergenza e oltre

Snodo cruciale dei Corsi di Laurea professionalizzanti in servizio socia- le, i tirocini sono stati interrotti nei mesi del lockdown e pesantemente ral- lentati successivamente. In questa congiuntura avversa, sono state sviluppate iniziative non convenzionali, alcune delle quali potenzialmente innovative. L’articolo si concentra sull’esperienza toscana (aprile 2020/febbraio 2021), analizzandola con riferimento al dibattito teorico-metodologico sul tirocinio e nel contesto delle sfide poste dall’emergenza sanitaria. L’articolo contri- buisce alla stabilizzazione della sperimentazione oltre la fase di emergenza, al trasferimento della pratica e più generalmente al rinnovato dibattito sulla formazione a distanza in servizio sociale.The internships in social work – a key-activity of the Degree Programs all over the world – have been suspended in the lockdown period and then slowened down. Several unconventional initiatives have been developed to cope with this adverse conjuncture. This article focuses on the Tuscan experience (April 2020/February 2021) which is analyzed within the debate on field education and the challenges of pandemic. The article contributes to stabilize the sperimentation beyond the emergency phase, to transfer the Tuscan practice and more generally to develop the debate on distance education in social work