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Lenalidomide in Transfusion-Dependent IPSS Low- or Intermediate-1-Risk Myelodysplastic Syndromes and Isolated Del(5q): Results of a European Postauthorization Safety Surveillance Study
Get PDFBackground: This noninterventional postauthorization safety study assessed the safety and effectiveness of lenalidomide in patients with transfusion-dependent, International Prognostic Scoring System (IPSS) Low- or Intermediate (Int)-1-risk myelodysplastic syndromes (MDS) associated with isolated deletion of 5q (del[5q]) who were treated in routine care. Patients and Methods: Eligible adult patients in the lenalidomide cohort had transfusion-dependent, IPSS Low- or Int-1-risk MDS and isolated del(5q) and had received ≥ 1 dose of lenalidomide between 2014 and 2022. The primary endpoint was the 24-month cumulative incidence of acute myeloid leukemia (AML) progression. Overall survival (OS) was estimated by Kaplan–Meier analysis and safety data were collected. Results: In total, 296 patients received ≥ 1 dose of lenalidomide (lenalidomide cohort, safety population) and 277 had received ≥ 1 complete cycle of lenalidomide (primary population). In the safety population, 44.3% of patients completed 3-year follow-up and 55.1% discontinued, with 33.1% discontinuing due to death. In the primary population, 24-month cumulative incidence of AML progression was 12.7% (95% confidence interval, 8.9%-17.1%) and estimated OS probability was 78.3% at 24 months and 63.9% at 36 months. Grade 3/4 treatment-emergent adverse events were experienced by 67.2% of the safety population, and these led to discontinuation in 35.5% of patients. There were no new safety signals. Conclusion: These real-world data support the established benefit-risk profile of lenalidomide in transfusion-dependent IPSS Low- or Int-1-risk MDS with isolated del(5q)
Probabilistic supervenience and agential possibilities
No full textCompatibilist libertarianism proposes a new solution to the problem of an apparent incompatibility of free will and determinism. It drives a wedge between ontological levels and claims that free will is possible as a higher-level phenomenon even if the fundamental physical level is governed by determinism. After highlighting an inconsistency in the current version of compatibilist libertarianism, we discuss how one of its essential metaphysical assumptions (in particular: supervenience) can be modified in order to avoid this problem. Finally, we discuss the pros and cons of pushing the position to the limits in this way
Protein C in adult patients with sepsis: from pathophysiology to monitoring and supplementation
Get PDFProtein C (PC) plays a crucial role in modulating inflammation and coagulation in sepsis. Its anticoagulant and cytoprotective properties are critical in mitigating sepsis-induced coagulopathy, which is associated with high mortality rates. In sepsis, low levels of PC are associated with an elevated risk of multiple organ dysfunction and increased mortality. Routine monitoring of PC levels is not widely implemented but appears relevant in selected populations, such as patients with purpura fulminans, sepsis-induced coagulopathy (SIC), disseminated intravascular coagulopathy (DIC) or hyperinflammatory septic shock phenotypes. Treatment with PC has been limited to PC concentrate approved for paediatric use in congenital PC deficiencies and purpura fulminans, while the efficacy of PC supplementation in sepsis remains a subject of debate. Considering the physiological significance of PC and its role in sepsis pathophysiology, additional studies are necessary to fully elucidate its therapeutic efficacy in specific clinical settings
Next-Generation Robotic Vision Systems for Quality Assurance in Plastics and Packaging
No full textThis paper introduces an innovative robotic solution to quality assurance and product packaging to reduce human effort while ensuring high-quality results. The proposed system efficiently handles and inspects the product by utilizing the mounted cameras that feed the advanced computer vision models that can detect any fault in the product, which it can then package. A unique feature of our system is the custom-designed palletising island and vacuum gripper to handle products during quality control and packaging. Rigorous testing and experiments with plastic products have shown that our system matches, and in some aspects, surpasses the proficiency of experienced human operators in both efficiency and accuracy
Identification of alexamorelin consumption biomarkers using human hepatocyte incubations and high-resolution mass spectrometry
No full textAlexamorelin is a synthetic peptide and growth hormone secretagogue (GHS) with potential performance-enhancing properties, making its use and abuse a topic of interest in clinical research and doping monitoring. Alexamorelin mimics the natural peptide hormone ghrelin by binding to the GHS type 1a receptor (GHS-R1a) in the pituitary gland, thereby promoting endogenous growth hormone release. Identifying alexamorelin and/or its metabolite biomarkers is crucial for effective doping controls. The purpose of this study was to determine and characterize biomarkers associated with alexamorelin intake. In silico metabolite predictions were performed using GLORYx freeware, and in vitro incubations were conducted with pooled human hepatocytes from 10 donors. Samples were analyzed using liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS), with data processed through Thermo Scientific's Compound Discoverer. GLORYx predicted 21 single-reaction metabolites. N-Acetylation was identified as the primary transformation, with the highest probability score (98%), and occurring either at the C-terminal Ala or the N-terminal Lys. Other predicted transformations included N-oxidation, hydroxylation, amide hydrolysis, oxidative deamination, and phase II N-glucuronidation, with probability scores below 40%. All these transformations were predicted to occur at the two C-terminal (Ala or His) or N-terminal (D-Phe or Lys) amino acids. After 3 h of incubation with hepatocytes, only one metabolite (known as examorelin or hexarelin) was detected, resulting from the C-terminal cleavage of the Ala amino acid; this metabolic reaction is mediated by a carboxypeptidase. The alexamorelin signal decreased approximately 150-fold after 3 h, indicating significant hepatic metabolism. However, examorelin itself is a commercially available GHS secretagogue, and thus, it is not specific to alexamorelin consumption. Detecting alexamorelin remains critical to documenting its use
Soil temperature and moisture near downed trees and log barriers 5 years after a wildfire
Get PDFBackground: Forest recovery from natural disturbances is often linked to the biological legacies left in the aftermath. In the case of forest fires, coarse woody debris, and specifically downed logs, is recognized as preferential sites for forest regeneration, for the improved environmental conditions around them. In this study, we monitored the effect of barriers made of downed logs on near-surface (5 cm depth) soil temperature and soil moisture during the summer of 2022 (9 dates) in a conifer forest in Central Italy burnt in 2017. We took measurements at various distances from the barriers to assess the spatial extent of their influence on soil moisture and temperature. Leveraging the presence of log erosion barriers in the field, we compared the effects of naturally fallen (n = 14) and artificially placed (n = 19) logs. Results: We recorded lowest soil temperature and soil moisture in the immediate proximity of the logs, with values not significantly different from control points at a distance of one time the height of the barriers. This pattern was consistent throughout the summer, regardless of the type of barrier (natural/artificial). The decrease in soil temperature is probably caused by the interception of solar radiation, while the decrease in soil moisture is counterintuitive, and would require further investigation. The type of barrier did not influence soil temperature, but we recorded lower moisture around artificial barriers, suggesting that their positioning may have altered soil moisture retention capacity. Conclusions: From a management perspective, logs may be considered preferential sites for natural or artificial regeneration. Nonetheless their effect on near-surface soil moisture and temperature fades within a short distance, and their influence may be either positive or negative for natural regeneration, depending on the local limiting factors
On the Dynamics of Masonry Church: Discontinuous and Continuous Approaches
No full textIn a period characterized by the urgent need of ensuring an adequate safety level for the existing buildings according to the present standard codes, the stability evaluation of masonry structures against hazard events has become even more a current challenge. Although the high versatility and durability of masonry, evident difficulties in the structural assessment have been induced by factors such as lack of information in the materials’ properties, irregular geometries, time ageing. To tackle this problem, many modelling techniques in structural analysis have developed, thanks to many scientific studies available in literature. Nevertheless, computational time, discretization procedure, masonry behaviour, contact surface characteristics, loading application, the suitability of geometry complexity, could represent the negative principal aspects. Therefore, the most innovative modelling approaches are critically discussed in this paper. In particular, the aim of this research is to compare the efficiency of a Finite Element (continuous) Method and a Distinct Element (discontinuous) one, both applied for the numerical simulation under lateral loading conditions of a case study, severally damaged by the 2016 Central Italy earthquake. The continuous method is analysed with the Midas FEA NX©. In parallel, the discontinuous methods are studied with 3DEC© and LMGC90© software, where, in turn, different contact conditions are employed. Finally, from this investigation, the main Pros and Cons are highlighted for each method. In detail, the reliability of the discontinuous method could be observed in the accuracy of the failures pattern replicating. On the other hand, the continuous method should allow a fast procedure in the model setting, then remaining as a solution for a preliminary study on the dynamics of the structure
Valutazione dell'efficacia e del ridotto impatto ambientale della telemedicina impiegata quale tecnica di consultazione medica nella celiachia rispetto alle consultazioni tradizionali in presenza
No full textBackground: La pandemia da SARS-CoV-2 ha incentivato l’uso della telemedicina nei follow-up clinici. Questo studio valuta efficacia e impatto ambientale della telemedicina (TM) rispetto alle visite in presenza (FTF) in pazienti pediatrici con celiachia.
Metodi: Pazienti celiaci tra 2-16 anni, seguiti presso il nostro ambulatorio, hanno ricevuto una visita di follow-up FTF o TM, tramite Google Meet. Sono stati raccolti dati su CO2 emessa, costi e soddisfazione, tramite un modulo online. L’impronta ambientale è stata stimata usando 157g di CO2/ora per la TM, e specifici calcolatori per i mezzi di trasporto delle FTF. I partecipanti TM hanno compilato anche il questionario TUQ. Risultati: Su 654 pazienti invitati, 139 hanno dato consenso; 8 esclusi per dati incompleti. La coorte finale ha incluso 131 pazienti (58 TM, 73 FTF). Nessuna differenza significativa tra i gruppi per età, genere, aderenza alla dieta (CDAT). Il tempo visita è risultato inferiore in TM (30 min vs 75 min, p<0.001), così come le emissioni di CO2 (0,08 kg vs 24,00 kg, p<0.001). I giorni lavorativi persi erano minori in TM (10 vs 43, p<0.001). I costi medi erano inferiori in TM (€0,55 vs €15,7, p<0.001). I punteggi del TUQ mostrano alta soddisfazione e usabilità della TM
Conclusioni: La telemedicina si conferma una valida alternativa alle visite tradizionali nei pazienti pediatrici con celiachia. Riduce tempi, costi e impatto ambientale, mantenendo un’elevata soddisfazione. Offre benefici in termini di qualità assistenziale e sostenibilità.Abstract
Background: Healthcare systems contribute significantly to greenhouse gas emissions, with patient travel accounting for approximately 10% of this footprint [1]. Telemedicine (TM) has emerged as a viable solution to reduce emissions. This study aimed to compare the environmental impact, costs, and satisfaction associated with TM versus face-to-face (FTF) visits for follow-up of pediatric patients affected with celiac disease (CD). Methods: All children with a diagnosis of CD (2-16 years) attending follow-up visit were invited to choose between FTF or TM visits conducted via Google Meet. Data on carbon footprint, cost, usability and satisfaction [Telehealth Usability Questionnaire (TUQ)], and Celiac Dietary Adherence Test (CDAT) were collected using a Google Form.
Results: From March 2023 to November 2024, 654 eligible patients were invited and 131 were analyzed, after excluding who refused to participate and incomplete data (58 TM, 73 FTF). There was no significant difference in baseline characteristics between the two groups (gender, age and respondent: mother, father, adolescent or child, P: NS). CDAT scores were similar in TM and TFT groups (p = 0.9). TM visits were shorter (median 30, 25-40 min) than FTF (75 |55;95| min) (p < 0.001). CO2 emissions were significantly lower for TM than for FTF (0.08 |0.07-0.11| vs. 24.00 |10.50-39.00| kg) (p < 0.001). Lost working days (10 [18.9%], 43 [81.1%]; p < 0.001) and total costs (€0.55, €15.7; p < 0.001) were also lower for TM than for FTF. The median TUQ scores indicated high overall satisfaction (Median scores: Ease of Use and Learnability: 21, Satisfaction and Future Use: 26, Interface Quality: 25, respectively) resulting in highest ratings. However, Reliability score was low (median score: 16), suggesting potential issues with system stability or consistency in user experience.
Conclusions: TM offers a sustainable alternative to traditional follow-up visits for CD, reducing CO2 emissions, costs, and patient burden in terms of working days and time consuming. The patient’s satisfaction is very high. The findings of the present study support the wider use of TM in CD anagement, aligning healthcare practices with environmental sustainability goals
Artificial intelligence and sustainability reporting in practice: projections from an intellectual capital perspective
No full textPurpose – This paper aims to explore the possible interactions between artificial intelligence (AI), intellectual capital (IC) dimensions – human, organizational and relational – and sustainability reporting practices. While AI is increasingly recognized as a transformative technology with the potential to reshape decision-making, knowledge management and reporting processes, limited empirical research has examined how it influences the human, organizational and relational resources underpinning sustainability disclosure. Design/methodology/approach – This study adopts a qualitative case study approach focusing on two Italian medium-sized manufacturing firms that prepare sustainability reports and are initiating AI adoption. Data were collected through semi-structured interviews with those responsible for sustainability reporting and triangulated with additional interviews, corporate documents and sustainability reports to ensure a comprehensive analysis. Findings – The results show that AI adoption in sustainability reporting is perceived to reshape human, organizational and relational capital, generating both opportunities and tensions. Dual pathways of human capital development emerge, while the evolution of organizational capital is expected to depend on the degree of information system integration and, particularly in medium-sized enterprises, on the responsiveness and timeliness of external technology providers. AI is envisaged to enhance sustainability reporting accuracy and comparability but may undermine contextual interpretation and the interactive use of sustainability reporting as a space for dialogue and learning. Finally, it expands stakeholder engagement, though it carries the risk of challenging authenticity and trust. Originality/value – This study contributes to the growing literature on AI in sustainability reporting by providing empirical evidence of how AI adoption may influence the configuration and development of IC. It further extends research on IC management by illustrating how AI can redefine the knowledge resources implicated in sustainability disclosure practices
Co-solvent strategy for rechargeable post-lithium metal batteries
No full textThe potential increase in cost of lithium-ion batteries owing to the limited supply of lithium has prompted investigations into alternative and complementary rechargeable batteries that use post-lithium charge carriers with higher elemental abundance. However, achieving highly reversible post-lithium metal anodes with sufficient kinetics remains challenging. The addition of co-solvents to conventional electrolytes is emerging as an important strategy to resolve these issues. In this Perspective, we discuss the progress of the co-solvent strategy for sodium, potassium, magnesium, calcium, zinc and aluminium post-lithium metal batteries. The coordination ability of co-solvents with post-lithium charge carriers is presented as a useful guide for selecting co-solvents for the respective battery electrolytes, owing to its correlation with several influential factors that affect the electrochemical performance of the metal anodes, such as solvation structure, de-solvation process and solid electrolyte interphase formation. Additionally, a discussion is provided on the importance of unravelling the effects beyond the solvation sheath of cationic charge carriers and for the development of sustainable electrolytes