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Capturing Information About Multiple Sclerosis Comorbidity Using Clinical Interviews and Administrative Records: Do the Data Sources Agree?
Background/Objectives: Multiple sclerosis (MS) is often associated with comorbidities that affect clinical outcomes. Data on comorbidities can be sourced from self-reports, medical records, and administrative databases. The gold standard for collecting such data is prospective clinical collection, as in clinical trials, but this is not feasible in large epidemiological studies. This study aimed to assess the agreement between two data sources, clinical interviews and administrative records, identifying major comorbidities in people with MS (pwMS). Methods: We evaluated the agreement between clinical interview data and administrative records in pwMS enrolled at two sites (2021–2022). Seven comorbidities were investigated: depression, anxiety, diabetes, hypertension, autoimmune disease, chronic lung disease, and hyperlipidemia. We used kappa (κ), sensitivity, specificity, and predictive values to assess agreement. Results: The frequency of comorbidities varied between the sources. Administrative data often underestimated hypertension, autoimmune diseases, hyperlipidemia, and anxiety, but over-reported depression. It had high sensitivity for diabetes (80%) and moderate sensitivity for hypertension (62%). The agreement for diabetes (κ = 98.9%, PABAK = 0.98, positive agreement = 83.3%) and hypertension (κ = 89.8%, PABAK = 0.80, positive agreement = 70.8%) was high. Conclusions: The agreement between administrative data and clinical interviews was excellent for diabetes and hypertension. For other conditions, such as psychiatric, hyperlipidemia, and autoimmune comorbidities, administrative data had lower sensitivity, and often under-reported or misclassified the data
Mechanics-Based Probabilistic Modeling of Crack-Induced Failures in Glass and Corroded Cables
The presence of cracks and defects in materials plays a critical role in the damage and
failure mechanisms of materials and structures, significantly affecting residual strength and durability. Understanding and modeling the propagation of such discontinuities is essential to ensure structural safety, particularly in scenarios involving slow or cumulative loading. This thesis investigates the effect of cracks in two distinct but related contexts, both governed by progressive degradation processes: static fatigue of structural glass and the progressive failure of cables with pitting corrosion. Both phenomena are addressed through probabilistic mechanical approaches, with the aim of improving the understanding of the failure mechanisms and supporting the development of more reliable design criteria.
The first part of the thesis investigates static fatigue failure resulting from the subcritical
growth of surface cracks in glass panes subjected to wind loads. Most standards reduce the design strength of glass by introducing a modification coefficient kmod in order to account for static fatigue due to subcritical propagation of surface cracks and nominal duration equivalent, in terms of damage, to the actual loading conditions. For wind actions on glass plates, kmod and the nominal durations are based on tradition and practice and are not calibrated from real data. Here, a mechanics-based probabilistic approach is proposed to define modification coefficient and nominal durations based on long-term cumulative wind data relevant to the European context. Wind velocity records from anemometric stations in Italy are used to derive probabilistic distributions, which are incorporated into subcritical crack growth equations to evaluate the modification coefficient as a function of the return period of the wind action. Additionally, kmod is calculated directly through direct integration of available time histories of mean and peak wind velocities. The resulting values are compared with the prescriptions provided by existing design standards. The overall findings are analyzed and interpreted in the concluding section.
The second part of the thesis examines the progressive failure of cables composed of wires affected by pitting corrosion, which induces localized pits on the metal surfaces resulting in the formation of cracks and stress concentration/intensification phenomena. The analytical models in the literature typically schematize the cable as a fiber bundle, with the static strength of wires assumed as a random variable and the effect of corrosion introduced according to a strength criterion, thereby neglecting possible brittle fracture mechanics failures. Here, a fiber bundle model made of corroded wires is formulated in order to investigate the critical force-displacement response of the cable, considering both net cross-section and LEFM criteria for the wire's collapse as well as the corrosion variability inside the cable through the introduction of a probability distribution function of the crack depth ratio. Using both criteria allows to introduce a dimensionless group, defined as brittleness number s_e, that controls the transition between brittle and ductile wire failure on varying the damage size and depends on
nominal strength, fracture toughness and diameter of the wire. The equilibrium critical load of a cable made of wires that fail by a joint criterion is obtained. The normalized equilibrium load is independent of the nominal strength but it depends on the brittleness number s_e and on the probability distribution of the initial damage. Depending on the value of the brittleness number, the wire failure mode changes from brittle to ductile. As a consequence, the maximum strength and ductility of the cable changes on varying s_e. The effects of the corrosion probability distribution, in terms of its statistical moments, on cable strength and the brittleness number is analyzed. The model is then applied to the Polcevera Viaduct case. The main outcomes and implications of the formulation are discussed in the conclusions
Investigating the role of Tgds in ATDC5 cells’ chondrogenic differentiation
Catel–Manzke syndrome (CMS) is a rare autosomal recessive genetic disorder characterized by a symptomatology known as "Pierre-Robin sequence": patients exhibit a small mandible, cleft palate, and a tendency of the tongue to obstruct the airway and digestive tract. Another characteristic is the presence of an additional phalanx affecting the index finger, resulting in finger deviation (clinodactyly). Other malformations have been observed in the cardiac, articular, and other skeletal regions. CMS is related to mutations in the TGDS (dTDP-D-glucose 4,6-dehydratase) gene, located on chromosome 13. The specific function of TGDS in vertebrates is unknown.
We used ATDC5 cells, a well-established model for studying chondrogenesis, to evaluate the effect of TGDS knockdown. ATDC5 Tgds knockdown cells were generated using lentiviral shRNA trasduction (shRNA49). Cells were stimulated with ITS (insulin/transferrin/selenium) for up to 21 days to induce chondrogenesis. Chondrogenic differentiation was assessed by analyzing the expression levels of specific marker genes - Sox9, Acan, Col2a1, and Col10a1- via RT-qPCR.
RT-qPCR analysis confirmed efficient knockdown of TGDS expression in shRNA49 cell line compared to the control. During chondrogenic induction, shRNA49 knockdown led to a consistent reduction in the expression of key markers - Sox9, Acan, Col2a1, and Col10a1. This indicates an impairment of the chondrogenic process in shRNA49 cells. As further confirmation of these findings, Alcian blue staining revealed a marked decrease in proteoglycan production in shRNA49 cells compared to the scrambled control, consistent with reduced chondrogenic differentiation.
Taken together, these results suggest that TGDS plays a functional role in promoting chondrogenic differentiation
Where Has God Gone in the Vernacular Renderings of Lanfranc’s Chirurgia magna?
From the fourteenth century onward, Latin surgical treatises were increasingly frequent translated into vernacular languages. This increased interest for the translation of surgical texts addressed the needs of surgeons who lacked academic training but desired to learn the techniques and the remedies of the ‘masters’ of the past. This primarily practical approach to surgery is typically reflected in the structure of the vernacular renderings of surgical works, which tend to abbreviate the Latin original by omitting all the parts considered scarcely useful in everyday-surgical practice (e.g., references to medical authorities, long discursive passages, theoretical disputes). A common feature of large Latin surgical (and, in general, medical) treatises was the presence of an initial dedication to God, in which the author invoked the divine help to be able to complete his writing endeavor, and of an explicit thanking God for allowing the accomplishment of this work. Moreover, additional invocations to God and references to faith could be inserted in other parts the text. In this study, the English and German vernacular renderings of Lanfranc of Milan’s Chirurgia magna will be taken into consideration and contrasted with their source with respect to their treatment of the ‘religious’ passages included in the Latin original, in order to outline the relationship between faith and vernacular surgery in the Late Middle Ages
Electrospun mats for the cleaning of paints in Cultural Heritage
Traditional methods of cleaning of paints involve the use of abrasive techniques or chemical agents, such as solvents, which can pose risks to the underlying materials. These methods can lead to undesired changes in surface texture, to degradation of the original layers, or the introduction of harmful residues. This highlights the need for alternative, non-invasive cleaning techniques that can be precisely controlled and tailored to the specific needs of cultural artifacts [1-2]. This study investigates the potential of electrospun mats made from Agarose/PEO and PVA for the removal of repaints and the cleaning of paints, focusing on the use of benzyl alcohol as a solvent. The electrospinning technique, a versatile and efficient method for producing nanofibrous materials, was employed to fabricate the mats characterized by their high surface area, porosity, and fine structure, making them ideal for delicate cleaning tasks [3]. The mats' morphology and mechanical properties were thoroughly examined using Scanning Electron Microscopy (SEM) and mechanical testing to ensure their suitability for conservation purposes. Electrospun mats were tested in laboratory conditions to assess their stability in benzyl alcohol, a solvent commonly used in conservation to remove repaints. Swelling and deswelling behaviors were first analyzed on two model surfaces: a worthless painted canvas and a glass slide coated with a pigment layer. Then, mats were tested in situ on an ancient wooden paint undergoing restoration at the Soprintendenza Archeologia Belle Arti e Paesaggio per la città metropolitana di Genova e la provincia di La Spezia. The cleaning process was monitored through macro photography and cross-sectional imaging to assess the mats' efficiency in removing repaints and varnish without damaging the underlying original paint layer. Furthermore, SEM-EDS analysis was conducted on the used mats to understand the cleaning mechanism and examine the material removed from the artwork layers.
The results suggest that electrospun mats offer a promising solution for the non-abrasive, targeted cleaning of cultural heritage, effectively removing repaints and dirty varnish without compromising the integrity of the original artwork. This method addresses key challenges in the field of conservation, including precision, no residues, and the preservation of fragile materials, presenting a valuable tool for the restoration of cultural heritage
Medication-resistant epilepsy is associated with a unique gut microbiota signature
Objective: Dysfunction of the microbiota–gut–brain axis is emerging as a new pathogenic mechanism in epilepsy, potentially impacting on medication response and disease outcome. We investigated the composition of the gut microbiota in a cohort of medication-resistant (MR) and medication-sensitive (MS) pediatric patients with epilepsy. Methods: Children with epilepsy of genetic and presumed genetic etiologies were evaluated clinically and subgrouped into MR and MS. Age-matched healthy controls (HCs) were also recruited. A food diary was used to evaluate nutritional habits, and the Rome IV questionnaire was used to record gastrointestinal symptoms. The microbiota composition was assessed in stool samples through 16S rRNA. α-Diversity (AD) and β-diversity (BD) were calculated, and differential abundance analysis was performed using linear multivariable models (significance: p.adj <.05). Results: Forty-one patients (MR:MS = 20:21) with a mean age of 7.2 years (±4.6 SD) and 27 age-matched HCs were recruited. No significant differences in AD were found when comparing patients and HCs. Significant positive correlation was found between AD and age (Chao1 p.adj =.0004, Shannon p.adj =.0004, Simpson p.adj =.0028). BD depicted a different bacterial profile in the epilepsy groups compared to HCs (MS vs. HC: Bray–Curtis F = 1.783, p =.001; Jaccard F = 1.24, p =.001; MR vs. HC: Bray–Curtis F = 2.24, p =.001; Jaccard F = 1.364, p =.001). At the genus level, the epilepsy groups were characterized by a significant increase in Hungatella (MS vs. HC: +4.95 log2 change; MR vs. HC: +6.72 log2 change); the [Eubacterium] siraeum group changed between the MR and MS subgroups. Significance: Epileptic patients display unique gut metagenomic signatures compared to HCs. Moreover, a different ratio of the butyrate-producing [Eubacterium] siraeum group suggests dissimilarities between patients based on the response to antiseizure medications
Towards Effortless Prosthetic Grasping through a Vision-based Shared Autonomy Pipeline
Upper-limb amputations significantly impact the quality of life, and while prosthetic devices can restore some lost functionalities, control complexity remains a major barrier for effective user-driven prosthesis control. Most commercial prostheses are based on electromyography (EMG) or mechanomyography (MMG), relating these input signals to the velocity of the prosthesis motors. When more than one degree-of-freedom is available, the Sequential Switching and Control paradigm is used. In this case, only one joint at a time is driven and the user gives an explicit input signal to switch between the different degrees of freedom, resulting in a cumbersome control. Therefore, relieving the user from complex control input modalities is of high interest in prosthetics. To address such limitations, this PhD project proposes a shared autonomy pipeline that integrates computer vision with the standard EMG-based mechanism for prosthesis control, thus reducing the cognitive burden on the user and increasing the prosthesis dexterity. This work starts with the exploration of different camera positioning (i.e., eye-in-hand vs. egocentric), followed by its integration into the prosthetic device. As for the prosthesis control, two different entities can be identified: the thumb and the wrist. Initially, they are tackled separately, then, as a final outcome, they are integrated into a unique pipeline achieving closed-loop wrist control during the approach followed by hand and thumb pre-shape prediction for grasping. Given the scarce availability of visual data in the prosthetic scenario, and to avoid tedious data collection, this work follows the sim-to-real approach, where the models are trained on synthetically generated data and deployed in a zero-shot fashion in the real world. Therefore, I validate each component of our pipeline first in simulation and then in the real world. In addition, as a further contribution, a novel pipeline exploring a fully-autonomous control rather than shared user-machine collaboration is proposed. This approach leverages the knowledge gained from methods in robotics and introduces a novel framework to adapt them for prosthetic applications. The method is tested both on able-bodied and amputee subjects to assess system's usability and a pilot study on cognitive load shows that the proposed pipeline has the potential to reduce the mental effort on the user.
Overall, the results collected throughout the PhD suggest that vision-based prosthetic grasping systems have the potential to both reduce the cognitive burden on the user and to foster a more natural grasping action. These characteristics are crucial for easing the use of prosthetic hands and minimizing the rejection of the prosthetic device. This work paves the way for further use of Artificial Intelligence methods for the control of prosthetic devices in more complex scenarios, such as long-horizon tasks and bimanual manipulation
Unravelling the complexity of respiratory involvement in Duchenne muscular dystrophy: An urgent call for a collective translational approach
Il ruolo delle istituzioni. I progetti di ricerca europei e le nuove sfide interdisciplinari.
I principi di Equality, Diversity and Inclusion (d’ora in poi EDI) abbracciano diverse dimensioni, come il genere, la disabilità, la razza/etnia, la religione, l’orientamento sessuale, l’età e le loro intersezioni. L’EDI sta assumendo un’importanza crescente in ambito accademico, ove sempre più si diffonde l’idea che le istituzioni universitarie debbano creare al loro interno comunità inclusive, in cui le singole persone possano vedere le proprie identità riconosciute, rispettate e celebrate e contribuire più in generale alla trasformazione della società. A tal fine, il principio cardine dell’accessibilità deve permeare in maniera ampia l’istituzione universitaria, toccando la cultura istituzionale e organizzativa, al pari della ricerca, dell’insegnamento e della didattic
La Corte costituzionale torna su perequazione finanziaria e coordinamento della finanza pubblica allargata, tra esigenze di tutela della autonomia degli enti territoriali locali e necessità di contenimento della spesa corrente
Con la sentenza n. 45 del 2025 la Corte costituzionale è stata chiamata a pronunciarsi sulla legge statale di bilancio per il 2024 per la lamentata lesione, sotto diversi profili, dell’autonomia finanziaria degli enti territoriali locali e, dunque, è torna a mettere ordine in materia di perequazione finanziaria, sottolineando
distinzioni e concetti che vanno al di là dell’individuazione dei corretti meccanismi legislativi e si proiettano sui ruoli che, dinanzi al complesso strumentario predisposto
dall’art. 119 Cost., lo Stato e gli enti territoriali sono chiamati a ricoprire