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Telerehabilitation for the treatment of nocturnal hypokinesia in people with Parkinson’s disease: a pilot study
No full textIntroduction: Nocturnal hypokinesia (NH) (i.e., reduced bed mobility) is common in people with Parkinson's Disease (PwPD), significantly affecting sleep quality. Physiotherapy showed encouraging results to treat this symptom but was poorly investigated. Moreover, telerehabilitation could be useful to increase treatment capillarity and to overcome logistic limitations. In this pilot study we investigated preliminary feasibility, safety and effectiveness of a telerehabilitation program in mild-to-moderate PwPD with NH. Materials and methods: Sixteen PwPD with disease stage < 4, presence of NH and no cognitive impairment, were enrolled and 12 completed the study. Participants underwent a 6-week telerehabilitation program though a digital remote video call platform. The rehabilitation program included progressive exercises performed during both remote supervised sessions with a physiotherapist and self-conducted sessions through video-tutorials. PwPD were evaluated before (T0) and after the program (T1) using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) parts I-IV, Parkinson's disease questionnaire 39 (PDQ-39), Parkinson's Disease sleep Scale (PDSS2), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) and Nocturnal Hypokinesia Questionnaire (NHQ). Results: Dropout rate was 25%. We found a significant improvement in PSQI score (p = 0.039, median difference: 2) and in item 2.9 of the MDS-UPDRS part II assessing NH (p = 0.026; median difference: 1). A tendency toward significance was found in NHQ score (p = 0.069). No significant adverse events were reported during treatment. Conclusion: Our pilot study showed that telerehabilitation could be a feasible, safe and effective option to improve NH and sleep quality in mild-to-moderate PwPD
Study of innovative technologies for the evaluation of the characteristics and quality of new generation pharmaceutical products
No full textThe quality control (QC) of pharmaceutical products represents one of the most critical aspects of the entire drug life cycle, from development through production to clinical application. It forms the foundation for ensuring that every medicinal product intended for patients is not only effective but also safe, stable, and consistent across different production batches. In an era marked by the rapid development of increasingly complex therapeutic modalities—including plasma-derived products, recombinant proteins, monoclonal antibodies, and nucleic acid–based vaccines—the challenges associated with pharmaceutical quality control have become significantly more demanding. Unlike small-molecule drugs, whose chemical and physicochemical properties can generally be assessed through relatively straightforward analytical techniques, biological and biotechnological products exhibit pronounced structural and functional heterogeneity. This complexity requires adopting multiparametric analytical approaches with high sensitivity and specificity, capable of detecting even subtle variations. The primary objective of QC is to ensure that each pharmaceutical product complies with stringent regulatory standards, providing consistent therapeutic performance while safeguarding patient health. This is achieved through a series of tests and validation processes that examine critical parameters such as identity, purity, potency, and stability—for both active pharmaceutical ingredients (APIs) and final formulations. The systematic identification and control of risks such as contamination, impurities, or manufacturing deviations prevent the release of non-compliant or counterfeit drugs that could compromise patient safety or cause adverse health effects.
QC therefore plays a central role not only in protecting public health but also in ensuring regulatory compliance and maintaining industry accountability. Global regulatory authorities—such as the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the World Health Organization (WHO)—impose rigorous protocols to guarantee that drugs consistently meet predefined quality parameters. This is particularly relevant for complex biologics and generics, where even slight variations in composition or structure can significantly affect efficacy or safety. Traditional QC strategies mainly focus on verifying product composition, biological activity, and shelf life. However, the heterogeneity of biological products calls for increasingly advanced testing methods aligned with international standards such as the European Pharmacopoeia, which mandate the identification of aggregates, degradation products, and structural anomalies. Classical analytical techniques are often inadequate to detect subtle molecular or structural variations arising from differences in raw materials, manufacturing processes, or storage conditions. Such variations can have significant clinical consequences, particularly for plasma-derived medicines such as human serum albumin (HSA) or innovative vaccine formulations developed during the COVID-19 pandemic. These challenges highlight the need for multiparametric analytical platforms capable of comprehensively evaluating the structural, functional, and rheological properties of pharmaceutical formulations. Given the increasing complexity of biological products, the pharmaceutical industry is increasingly relying on advanced analytical techniques—including high-performance liquid chromatography (HPLC), mass spectrometry, and microbiological testing—to detect trace impurities or degradation products and ensure product quality throughout shelf life.
Beyond regulatory compliance, these methods provide mechanistic insights into complex biological systems, support process optimization, improve batch-to-batch reproducibility, and promote the development of real-time, non-destructive monitoring techniques. Consequently, rigorous QC emerges as both a regulatory requirement and a scientific necessity—not only for batch release and post-marketing surveillance but also for fostering innovation, process optimization, and the reliability of safe and globally accessible therapies.
Building on this framework, the present research project was designed to develop and optimize a multi-target analytical approach for evaluating the quality and physicochemical properties of biologically derived pharmaceutical products, integrating complementary techniques capable of detecting pronounced and subtle compositional, structural, and functional variations critical for product quality. This strategy integrates thermogravimetry (TGA), rheology, and MicroNIR spectroscopy with advanced chemometric tools, enabling a comprehensive and multidimensional characterization of complex biological formulations and overcoming the limitations of conventional QC methods. The study examined two representative classes of products—COVID-19 vaccines and human serum albumin (HSA) solutions—and extended to the blood matrix, aiming to provide a unified multiparametric framework for evaluating advanced biological therapeutics. These products, characterized by structural complexity, sensitivity to formulation and production variables, and significant clinical implications, represent ideal candidates for an integrated analytical assessment.
All samples were analyzed by MicroNIR spectroscopy, enabling the non-destructive capture of their molecular signatures. For COVID-19 vaccines - including inactivated virus vaccines (AstraZeneca, Janssen), protein subunit vaccines (Nuvaxovid), and mRNA-based vaccines (Comirnaty, Moderna) - spectra were pretreated and analyzed using Principal Component Analysis (PCA) to reveal inherent patterns and optimize separation among formulations. The insights gained from PCA guided the development of Partial Least Squares Discriminant Analysis (PLS-DA) and Partial Least Squares (PLS) regression models, which were validated against relevant performance metrics. The PLS-DA models enabled reliable differentiation of vaccines according to their active ingredient and manufacturer, highlighting compositional differences associated with formulation and production processes. In parallel, the PLS regression model was developed for the quantification of the active component in mRNA-based vaccines (0.05, 0.1 and 0.2 mg/mL), demonstrating high predictive accuracy and linearity. These results confirm the potential of the spectroscopic–chemometric approach as a rapid, non-destructive, and robust analytical tool for both qualitative and quantitative quality assessment of vaccine formulations.
MicroNIR spectroscopy was also applied to HSA solutions, enabling the development of PLS-DA and PLS models capable of distinguishing products from two different manufacturers based not only on the production process but also on the origin of the plasma (national or international, obtained via plasmapheresis or whole blood). Furthermore, a quantitative PLS model was established to accurately determine the concentration of plasma protein (25%, 20% e 5%) in each solution, providing an integrated view of both qualitative and quantitative aspects of albumin products.
Rheological profiling complemented spectroscopic analysis for both vaccines and HSA solutions. Measurements included rotational viscosity at high (η200) and low (η1) shear rates, as well as viscoelastic parameters (G′ and G′′), providing information on flow behavior, elasticity, and potential effects on micro- and macro-circulatory dynamics. For HSA solutions, rheology was studied at concentrations of 25%, 20%, and 5%, comparing products from different manufacturers and plasma origins. These findings are particularly relevant from a clinical perspective, given albumin’s role in plasma volume regulation and microcirculatory dynamics, as well as the influence of concentration, manufacturing processes, and post-translational modifications on its functional performance.
Finally, thermogravimetric analysis (TGA) coupled with chemometrics was applied to both vaccines and HSA solutions. TGA allowed the identification and quantification of thermally induced decomposition processes, revealing differences in stability and composition. The synergistic integration of TGA, rheology, and spectroscopy within a chemometric framework allowed the development of a robust analytical platform capable of identifying key quality parameters and ensuring reproducible pharmaceutical performance consistent with manufacturing specifications.
Overall, this multi-analytical and chemometrically driven approach highlights the power of combining complementary techniques to assess quality, detect subtle differences, and develop predictive models, with direct applications to both vaccine evaluation and the standardization of albumin-based therapeutics.
Furthermore, during the research period at Claude Bernard University in Lyon, this multi-analytical approach was extended to the human blood matrix, to investigate potential differences between healthy individuals and patients affected by sickle cell disease (SCD). Building on preliminary studies, whole-blood samples were analyzed using MicroNIR spectroscopy, TGA, and rheology, and the results were compared with those from previous studies by the same research group that employed ectacytometry and viscosimetry to characterize rheological alterations in SCD. The combined analyses enabled the identification of subtle variations in protein content, red blood cell deformability, and plasma composition, which were then correlated with macroscopic rheological behavior. This integration provided a deeper understanding of how molecular and structural changes translate into altered blood flow properties, highlighting the versatility of a multi-analytical, chemometrics-driven strategy for investigating complex biological matrices.
In conclusion, the proposed approach demonstrates the potential of combining complementary techniques to assess the quality of pharmaceutical products systematically, detect significant differences, and develop predictive models. Its applications range from vaccine evaluation and albumin standardization to the study of pathological blood samples. By unifying spectroscopic, rheological, and thermal analyses, this work establishes a solid and robust platform for the characterization of complex biological medicines, supporting both scientific understanding and regulatory quality assurance, and providing innovative tools to improve batch reproducibility, manufacturing efficiency, and diagnostic applications
Mortality, cardiovascular and bleeding risk according to anticoagulant type in patients with atrial fibrillation and cancer. Insights from the Nationwide Italian START registry
No full textBackground. The optimal management of anticoagulation in atrial fibrillation (AF) patients with cancer remains unclear. Beyond thromboembolism these patients have an increased risk of cardiovascular events (CVEs) and bleeding due to their frailty condition. We investigated all-cause mortality, CVEs and any bleeding risk comparing direct oral anticoagulants (DOACs) and vitamin K antagonists (VKA).
Methods. AF Patients with cancer from the nationwide Italian START registry on treatment with oral anticoagulants were included. A propensity score matching (PSM) was performed. Results were expressed as hazard ratio (HR) and their 95% confidence interval (95%CI) for all-cause mortality using Cox regression analysis and as subdistribution HR (sHR) and their 95%CI for CVEs and bleeding risk taking account of competing risk using Fine-Gray analysis.
Results. 1,605 of 10,369 AF patients had cancer (median 78 years, 44.7% women). During a median follow-up of 729.8±597.4 days, 153 deaths, 177 CVEs and 90 bleedings occurred. After PSM, DOACs were associated with lower all-cause mortality (HR: 0.37, 95%CI: 0.23-0.58, p<0.001) and CVEs (sHR 0.58, 95%CI 0.39-0.84, p=0.005) risk, but not bleeding risk, compared to warfarin.
These results were more evident if patients treated with VKAs had a low anticoagulation quality (Time in Therapeutic Range <70%). In the subgroup analysis, we found a lower risk of all-cause of death and CVEs in patients treated with apixaban and dabigatran, and a higher risk of any bleeding in patients treated with edoxaban compared to VKA.
Conclusion: DOACs are associated with a lower mortality and CVEs risk compared to VKAs in patients with AF and cancer, without difference in bleeding risk
Fatigue performance of Ti6Al4V lattices: relative density as a partial quantitative predictor
No full textLattice structures realized through additive manufacturing have garnered increasing interest within both academia and industry in recent years. Various factors, including unit cell topology, base material, heat treatments, and relative density, significantly influence the overall behaviour of these architectured structures. This study specifically examines the compressive mechanical behaviour of solid-based gyroid lattices made of Ti6Al4V alloy through Laser Powder Bed Fusion (PBF-LB) technique. Specimens with four different relative densities were produced to investigate the impact of this parameter on the compressive behaviour (quasi-static and fatigue); furthermore, each relative density category included two sets of specimens to evaluate the effect of annealing and Hot Isostatic Pressing (HIP) as post-processing techniques. Micro-CT scans, microstructural, postmortem and finite element analyses were included to further evaluate the failure mechanisms and explain the observed experimental results. Furthermore, the behaviour documented in the present analysis has been correlated with a wide fatigue dataset retrieved from literature in an effort to dig deeper into the behaviour of these structures. The results, together with the retrieved dataset, allowed for a more comprehensive understanding also considering aspects such as yielding effect, surface roughness and notch mechanics. It has been proved that the use of optimized process parameters and cheaper heat treatments is able to match the beneficial effects expected by HIP. Furthermore, easy-to-use methodologies to account for the reduction in strength due to the change in relative density presented in the literature, such as effective and normalized stress, have been considered to evaluate their accuracy, but also their limitations
Three essays on inflation: a structuralist approach
No full textAfter several decades of low and stable inflation, Europe experienced a sharp inflationary spike beginning in 2021. The return of inflation sparked renewed debate in Macroeconomics. This dissertation develops a comprehensive theoretical and empirical investigation of the post-pandemic inflationary shock, with a specific focus on the European economy. The contribution to the literature is threefold: first, it shows how current disagreements about the causes, consequences and policy responses to inflation are rooted in an enduring theoretical dispute which can be traced back to the Great Inflation of the 1970s; second, it provides an analysis of the drivers and consequences of the recent inflationary episode across European Union (EU) and Euro Area (EA) countries, accounting for the significant heterogeneity in their economic structures and integration in global value chains; third, and most importantly, it develops an empirical model to investigate how price shocks are transmitted across production networks, using inter-country input-output data to identify the domestic and foreign sectors which are most critical to price stability in EU countries
An Echo of Sight: Generative Models for Audio-Visual Spatial Coherence
No full textWhile deep generative models have achieved remarkable success in synthesizing high-fidelity images, video, and audio, the next frontier is coherent multimodal synthesis. In the audio-visual domain, current research has largely focused on semantic ("what") and temporal ("when") alignment, while neglecting the equally critical dimension of spatial coherence ("where"). This omission creates a perceptual disconnect that breaks immersion, as the auditory world feels flat and detached from the visual space.
This thesis, guided by the principle of "An Echo of Sight", directly addresses this gap by investigating, developing, and advancing generative models that establish robust spatial coherence between audio and visual modalities. The work progresses through four core, interconnected contributions.
First, we establish an analytical foundation for spatial audio understanding. Through our work on the L3DAS23 challenge and dataset, we demonstrate that deep learning models can effectively extract and exploit the rich spatial cues embedded in 3D Ambisonics audio for complex analysis tasks, including 3D speech enhancement and sound event localization and detection.
Second, we transition from analysis to perceptual synthesis with StereoSync, a novel framework for spatially-aware video-to-audio (V2A) generation. This model is the first to leverage visual spatial cues, such as depth maps and object trajectories, to condition a latent diffusion model, successfully generating stereo audio that spatially pans and aligns with on-screen object dynamics.
Third, we address the "off-screen" problem by expanding the generative context to a full spherical environment. We introduce Con360-AV, a framework for joint audio-visual generation conditioned on a complete 360° space. By using panoramic saliency and novel geometric maps, the model generates specific audio-visual viewpoints that are coherently embedded within the larger, surrounding world.
Finally, we introduce the HA30K dataset, a large-scale collection of acoustic simulations, and develop a generative surrogate model that learns to approximate the solutions of the Helmholtz equation. This work demonstrates that a generative model can learn the complex physical laws connecting a visual "Sight" (the geometry of a space) to its physical "Echo" (the acoustic pressure field).
The proposed frameworks demonstrate significant quantitative improvements in spatial alignment, generative fidelity, and computational efficiency. In particular, StereoSync achieves state-of-the-art spatial tracking, Con360-AV demonstrates robust spatial control in a 360° context, and our physics-based surrogate achieves a nearly 5x speedup over traditional solvers in batch processing. Collectively, this research provides a comprehensive methodology for audio-visual spatial coherence and delivers foundational technologies for the next generation of immersive media, virtual reality, and engineering-focused "Acoustic Digital Twins"
Presupposition, assertion, and epistemic vigilance across development
No full textThis study investigates how linguistic framing—specifically, the use of presupposition versus assertion—affects the critical evaluation of incoming information across development. While presuppositions present content as taken for granted, assertions introduce information as new, leading to differing levels of epistemic scrutiny. Prior work has shown that adults are less likely to detect falsehoods when they are presupposed rather than asserted. This study explores whether similar framing effects operate in childhood, and whether children's sensitivity is modulated by Information Structure—specifically, topic–focus articulation. To this end, we tested three age groups (7-year-olds, 10-year-olds, and adults) using a truth-evaluation task involving short videos and spoken sentences that either asserted, focally presupposed, or topically presupposed false information. Results revealed that across all age groups, presuppositions increased the likelihood of accepting false statements as true, indicating their potential to mislead. However, this effect varied with age: compared to adults, the impact of topical presuppositions was especially pronounced in 10-year-olds, and this stronger effect was possibly present in 7-year-olds as well. The results have implications for theories of pragmatic development, linguistic models, and practices of epistemic vigilance, with practical relevance for understanding children's susceptibility to misleading or manipulative content
Systemic administration of the OGT inhibitor OSMI-1 normalizes hippocampal O-GlcNAcylation and improves recognition memory, redox balance, and brain mitochondrial homeostasis in a Rett syndrome mouse model
No full textProtein O-GlcNAcylation (O-GlcNAc) is a nutrient-responsive posttranslational modification (PTM). Proper regulation of brain O-GlcNAc levels is essential for the coupling between metabolic homeostasis and neuronal function. Abnormal O-GlcNAc levels in the brain are associated with neurodevelopmental and neurodegenerative diseases related to defects in energy metabolism. We investigated the levels and regulation of protein O-GlcNAc modification and related pathways through gene and protein expression analysis in the hippocampus of two wellestablished murine models of Rett syndrome (RTT), a monogenic neurodevelopmental disorder with metabolic components and a primary cause of severe intellectual disability in females. Increased protein O-GlcNAc levels, due to changes in the molecular machinery that controls O-GlcNAc production, transfer, and removal, were observed in the hippocampus of the two RTT mouse models (MeCP2-BIRD and MeCP2-308 models). Remarkably, systemic administration of the OGT inhibitor OSMI-1 restored O-GlcNAc brain homeostasis and rescued brain mitochondrial defects and redox alterations in the RTT mouse hippocampus. The OSMI-1 treatment also induced a normalization of the cognitive performance of RTT mice in novel object recognition tests and reduced peripheral oxidative stress. These findings provide new evidence of an imbalance in nutrient-sensing O-GlcNAc in the RTT mouse hippocampus, suggesting that restoring brain O-GlcNAc homeostasis might represent a promising therapeutic approach for RTT
Winding challenges and solutions in the INFN Falcon dipole project
No full textThe Falcon Dipole is a project led by the Italian Institute of Nuclear Physics (INFN), which aims tofabricate a 12 T short model of a Nb3Sn cos-theta accelerator dipole as part of the High Field Magnet (HFM) R&D program at CERN [1]. The status of the project is at the fabrication step of the first dummy coil in the industry and, in this paper, the results of the first campaign of winding tests conducted in the industry are presented. The winding process for the Falcon Dipole is challenging because the size of the Rutherford Cable used for the coils is comparable to the bore radius. This results in high bending and torsion stresses, making the cable structure unstable. To address these challenges, the previous 3D model has been modified to improve the winding feasibility. The setup has been prepared to monitor technical parameters that will help in modeling the coil geometry and identifying sources of critical issues. In this paper, the outcomes of the winding campaign are reported and the proposed changes to the coil end design to address the issues that arose are discussed
The garden as an alement of regeneration in the contemporary city Brief general considerations fro jury
No full textThe garden has re-emerged in contemporary urban discourse as a strategic device for regeneration, positioned between ecological infrastructure, public space, and cultural heritage. This contribution reflects on the role of the garden as an element of urban regeneration through critical considerations developed within the framework of the Call for Visions | Gardens: Regeneration Cells in Contemporary Cities. Drawing from the perspective of the jury, the paper does not aim to propose a unified model, but rather to outline recurring themes, tensions, and opportunities that emerge from the submitted visions.
Particular attention is given to the reinterpretation of the garden’s traditional characteristics - such as enclosure, limits, and symbolic value - in relation to current challenges including climate change, water scarcity, and the risk of greenwashing. The text discusses the balance between continuity and innovation, emphasizing the potential of gardens as adaptive, small-scale interventions capable of activating broader regenerative processes. It also addresses critical issues related to representation and the growing use of artificial intelligence in design visions, questioning the relationship between conceptual thinking and visual output.
Overall, the contribution frames the garden as a flexible and process-oriented regenerative device, capable of mediating between past and future, local identity and global challenges within the contemporary city