From inverted pendulum to N-link chain: inertial sensors-based assessment of movement kinematics and dynamics for functional evaluation and rehabilitation

Despite several clinical tests that have been developed to qualitatively describe complex motor tasks by functional testing, these methods often depend on clinicians' interpretation, experience and training, which make the assessment results inconsistent, without the precision required to objectively assess the effect of the rehabilitative intervention. A more detailed characterization is required to fully capture the various aspects of motor control and performance during complex movements of lower and upper limbs. The need for cost-effective and clinically applicable instrumented tests would enable quantitative assessment of performance on a subject-specific basis, overcoming the limitations due to the lack of objectiveness related to individual judgment, and possibly disclosing subtle alterations that are not clearly visible to the observer. Postural motion measurements at additional locations, such as lower and upper limbs and trunk, may be necessary in order to obtain information about the inter-segmental coordination during different functional tests involved in clinical practice. With these considerations in mind, this Thesis aims: i) to suggest a novel quantitative assessment tool for the kinematics and dynamics evaluation of a multi-link kinematic chain during several functional motor tasks (i.e. squat, sit-to-stand, postural sway), using one single-axis accelerometer per segment, ii) to present a novel quantitative technique for the upper limb joint kinematics estimation, considering a 3-link kinematic chain during the Fugl-Meyer Motor Assessment and using one inertial measurement unit per segment. The suggested methods could have several positive feedbacks from clinical practice. The use of objective biomechanical measurements, provided by inertial sensor-based technique, may help clinicians to: i) objectively track changes in motor ability, ii) provide timely feedback about the effectiveness of administered rehabilitation interventions, iii) enable intervention strategies to be modified or changed if found to be ineffective, and iv) speed up the experimental sessions when several subjects are asked to perform different functional tests.

Evaluation and management of demersal stocks in the Adriatic: the case of common sole (Solea solea, L.) in the northern and central Adriatic Sea

This PhD thesis aimed to assess the status of common sole, one of the main commercial stocks in the Adriatic Sea, using a mix of conventional and innovative techniques to provide more reliable estimates of stock status compared to past advice. First, a meta-analysis was carried out using data-poor assessment model to analyze the whole catch assemblage of rapido fishery. The outcomes were used to estimate rebuilding time and forecast catches under different harvest control rule scenarios, with a reduction of 20% of fishing effort being suggested as a way to allow most of the species to recover to sustainable levels. Secondly, an ensemble of data-rich assessment models was developed to better incorporate uncertainty by using alternative hypotheses of main parameters. This was the first time an ensemble of models has been used in the Mediterranean to provide management advice. Consistent with data-poor analysis results, the ensemble outcomes indicated that the common sole stock was showing a recovering trend probably due to the effective management actions underway in the area rather than the moderate effort reduction according to the actual management plan. Moreover, back-calculation measurements were used to fit and compare monophasic and biphasic growth curves through the use of non-linear mixed effects models. The analyses revealed that the fitting of the biphasic curve was superior, confirming the theory that growth in size would decrease as a consequence of reproductive effort. A stock assessment simulation showed how the use of the monophasic pattern would result in a critical overestimation of biomass that could lead to a greater risk of overfishing. As a final step, a simulation-testing procedure was applied to determine the best performing reference points using stock-specific characteristic. The procedure could be routinely adopted to increase transparency in reference points calculation enhancing the credibility of scientific advice.

Methodologies for the analysis and interpretation of environmental datasets from areas interested by offshore activities

The exploitation of hydrocarbon reservoirs by the oil and gas industries represents one of the most relevant and concerning anthropic stressor in various marine areas worldwide and the presence of extractive structures can have severe consequences on the marine environment. Environmental monitoring surveys are carried out to monitor the effects and impacts of offshore energy facilities. Macrobenthic communities, inhabiting the soft-bottom, represent a key component of these surveys given their great responsiveness to natural and anthropic changes. A comprehensive collection of monitoring data from four Italian seas was used to investigate distributional pattern of macrozoobenthos assemblages confirming a high spatial variability in relation to the environmental variables analyzed. Since these datasets could represent a powerful tool for the industrial and scientific research, the steps and standardized procedures needed to obtain robust and comparable high-quality data were investigated and outlined. Over recent years, decommissioning of old platforms is a growing topic in this sector, involving many actors in the various decision-making processes. A Multi-Criteria Decision Analysis, specific for the Adriatic Sea, was developed to investigate the impacts of decommissioning of a gas platform on environmental and socio-economic aspects, to select the best decommissioning scenario. From the scenarios studied, the most impacting one has resulted to be total removal, affecting all the faunal component considered in the study. Currently, the European nations are increasing the production of energy from offshore wind farms with an exponential expansion. A comparative study of methodologies used five countries of the North Sea countries was carried out to investigate the best approaches to monitor the effects of wind farms on the benthic communities. In the foreseeable future, collaboration between industry, scientific communities, national and international policies are needed to gain knowledge concerning the effects of these industrial activities on the ecological status of the ecosystems.

3D probability tomography: theoretical developments and applications to high-resolution geophysical prospecting

The theory of the 3D multipole probability tomography method (3D GPT) to image source poles, dipoles, quadrupoles and octopoles, of a geophysical vector or scalar field dataset is developed. A geophysical dataset is assumed to be the response of an aggregation of poles, dipoles, quadrupoles and octopoles. These physical sources are used to reconstruct without a priori assumptions the most probable position and shape of the true geophysical buried sources, by determining the location of their centres and critical points of their boundaries, as corners, wedges and vertices. This theory, then, is adapted to the geoelectrical, gravity and self potential methods. A few synthetic examples using simple geometries and three field examples are discussed in order to demonstrate the notably enhanced resolution power of the new approach. At first, the application to a field example related to a dipole–dipole geoelectrical survey carried out in the archaeological park of Pompei is presented. The survey was finalised to recognize remains of the ancient Roman urban network including roads, squares and buildings, which were buried under the thick pyroclastic cover fallen during the 79 AD Vesuvius eruption. The revealed anomaly structures are ascribed to wellpreserved remnants of some aligned walls of Roman edifices, buried and partially destroyed by the 79 AD Vesuvius pyroclastic fall. Then, a field example related to a gravity survey carried out in the volcanic area of Mount Etna (Sicily, Italy) is presented, aimed at imaging as accurately as possible the differential mass density structure within the first few km of depth inside the volcanic apparatus. An assemblage of vertical prismatic blocks appears to be the most probable gravity model of the Etna apparatus within the first 5 km of depth below sea level. Finally, an experimental SP dataset collected in the Mt. Somma-Vesuvius volcanic district (Naples, Italy) is elaborated in order to define location and shape of the sources of two SP anomalies of opposite sign detected in the northwestern sector of the surveyed area. The modelled sources are interpreted as the polarization state induced by an intense hydrothermal convective flow mechanism within the volcanic apparatus, from the free surface down to about 3 km of depth b.s.l..

New insights into methodology and interpretation of osteoarthritis. The study of Frassetto identified skeletal collection.

Osteoarthritis (OA) or degenerative joint disease (DJD) is a pathology which affects the synovial joints and characterised by a focal loss of articular cartilage and subsequent bony reaction of the subcondral and marginal bone. Its etiology is best explained by a multifactorial model including: age, sex, genetic and systemic factors, other predisposing diseases and functional stress. In this study the results of the investigation of a modern identified skeletal collection will be presented. In particular, we will focus on the relationship between the presence of OA at various joints. The joint modifications have been analysed using a new methodology that allows the scoring of different degrees of expression of the features considered. Materials and Methods The sample examined comes from the Sassari identified skeletal collection (part of “Frassetto collections”). The individuals were born between 1828 and 1916 and died between 1918 and 1932. Information about sex and age is known for all the individuals. The occupation is known for 173 males and 125 females. Data concerning the occupation of the individuals indicate a preindustrial and rural society. OA has been diagnosed when eburnation (EB) or loss of morphology (LM) were present, or when at least two of the following: marginal lipping (ML), esostosis (EX) or erosion (ER), were present. For each articular surface affected a “mean score” was calculated, reflecting the “severity” of the alterations. A further “score” was calculated for each joint. In the analysis sexes and age classes were always kept separate. For the statistical analyses non parametric test were used. Results The results show there is an increase of OA with age in all the joints analyzed and in particular around 50 years and 60 years. The shoulder, the hip and the knee are the joints mainly affected with ageing while the ankle is the less affected; the correlation values confirm this result. The lesion which show the major correlation with age is the ML. In our sample males are more frequently and more severely affected by OA than females, particularly at the superior limbs, while hip and knee are similarly affected in the two sexes. Lateralization shows some positive results in particular in the right shoulder of males and in various articular surfaces especially of the superior limb of both males and females; articular surfaces and joints are quite always lateralized to the right. Occupational analyses did not show remarkable results probably because of the homogeneity of the sample; males although performing different activities are quite all employed in stressful works. No highest prevalence of knee and hip OA was found in farm-workers respect to the other males. Discussion and Conclusion In this work we propose a methodology to score the different features, necessary to diagnose OA, that allows the investigation of the severity of joint degeneration. This method is easier than the one proposed by Buikstra and Ubelaker (1994), but in the same time allows a quite detailed recording of the features. Epidemiological results can be interpreted quite simply and they are in accordance with other studies; more difficult is the interpretation of the occupational results because many questions concerning the activities performed by the individuals of the collection during their lifespan cannot be solved. Because of this, caution is suggested in the interpretation of bioarcheological specimens. With this work we hope to contribute to the discussion on the puzzling problem of the etiology of OA. The possibility of studying identified skeletons will add important data to the description of osseous features of OA, enriching the medical documentation, based on different criteria. Even if we are aware that the clinical diagnosis is different from the palaeopathological one we think our work will be useful in clarifying some epidemiological as well as pathological aspects of OA.

Cyclic alternating pattern in sleep and its relationship to creativity

Background/Objectives: Sleep has been shown to enhance creativity, but the reason for this enhancement is not entirely known. There are several different physiological states associated with sleep. In addition to rapid (REM) and non-rapid eye movement (NREM) sleep, NREM sleep can be broken down into Stages (1-4) that are characterized by the degree of EEG slow wave activity. In addition, during NREM sleep there are transient but cyclic alternating patterns (CAP) of EEG activity and these CAPs can also be divided into three subtypes (A1-A3) according to speed of the EEG waves. Differences in CAP ratios have been previously linked to cognitive performances. The purpose of this study was to learn the relationship CAP activity during sleep and creativity. Methods: The participants were 8 healthy young adults (4 women), who underwent 3 consecutive nights of polysomnographic recording and took the Abbreviated Torrance Test for Adults (ATTA) on the 2 and 3rd mornings after the recordings. Results: There were positive correlations between Stage 1 of NREM sleep and some measures of creativity such as fluency (R= .797; p=.029) and flexibility ( R=.43; p=.002), between Stage 4 of Non-REM sleep and originality (R= .779; p=.034) and a global measure of figural creativity (R= .758; p=.040). There was also a negative correlation between REM sleep and originality (R= -.827; p= .042) . During NREM sleep the CAP rate, which in young people is primarily the A1 subtype, also correlated with originality (R= .765; p =.038). Conclusions: NREM sleep is associated with low levels of cortical arousal and low cortical arousal may enhance the ability of people to access to the remote associations that are critical for creative innovations. In addition, A1 CAP activity reflects frontal activity and the frontal lobes are important for divergent thinking, also a critical aspect of creativity.

Combined Evaluation of ST-segment Elevation in lead AVR and ST-segment Depression in other Leads Enhances Prediction of in-hospital Cardiovascular Death in Patients with Non ST-segment Elevation Acute Coronary Syndrome

Objective: To investigate the prognostic significance of ST-segment elevation (STE) in aVR associated with ST-segment depression (STD) in other leads in patients with non-STE acute coronary syndrome (NSTE-ACS). Background: In NSTE-ACS patients, STD has been extensively associated with severe coronary lesions and poor outcomes. The prognostic role of STE in aVR is uncertain. Methods: We enrolled 888 consecutive patients with NSTE-ACS. They were divided into two groups according to the presence or not on admission ECG of aVR STE≥ 1mm and STD (defined as high risk ECG pattern). The primary and secondary endpoints were: in-hospital cardiovascular (CV) death and the rate of culprit left main disease (LMD). Results: Patients with high risk ECG pattern (n=121) disclosed a worse clinical profile compared to patients (n=575) without [median GRACE (Global-Registry-of-Acute-Coronary-Events) risk score =142 vs. 182, respectively]. A total of 75% of patients underwent coronary angiography. The rate of in-hospital CV death was 3.9%. On multivariable analysis patients who had the high risk ECG pattern showed an increased risk of CV death (OR=2.88, 95%CI 1.05-7.88) and culprit LMD (OR=4.67,95%CI 1.86-11.74) compared to patients who had not. The prognostic significance of the high risk ECG pattern was maintained even after adjustment for the GRACE risk score (OR = 2.28, 95%CI:1.06-4.93 and OR = 4.13, 95%CI:2.13-8.01, for primary and secondary endpoint, respectively). Conclusions: STE in aVR associated with STD in other leads predicts in-hospital CV death and culprit LMD. This pattern may add prognostic information in patients with NSTE-ACS on top of recommended scoring system.

Quantitative susceptibility mapping as biomarker of neurodegeneration: methodological models and clinical applications

Quantitative Susceptibility Mapping (QSM) is an advanced magnetic resonance technique that can quantify in vivo biomarkers of pathology, such as alteration in iron and myelin concentration. It allows for the comparison of magnetic susceptibility properties within and between different subject groups. In this thesis, QSM acquisition and processing pipeline are discussed, together with clinical and methodological applications of QSM to neurodegeneration. In designing the studies, significant emphasis was placed on results reproducibility and interpretability. The first project focuses on the investigation of cortical regions in amyotrophic lateral sclerosis. By examining various histogram susceptibility properties, a pattern of increased iron content was revealed in patients with amyotrophic lateral sclerosis compared to controls and other neurodegenerative disorders. Moreover, there was a correlation between susceptibility and upper motor neuron impairment, particularly in patients experiencing rapid disease progression. Similarly, in the second application, QSM was used to examine cortical and sub-cortical areas in individuals with myotonic dystrophy type 1. The thalamus and brainstem were identified as structures of interest, with relevant correlations with clinical and laboratory data such as neurological evaluation and sleep records. In the third project, a robust pipeline for assessing radiomic susceptibility-based features reliability was implemented within a cohort of patients with multiple sclerosis and healthy controls. Lastly, a deep learning super-resolution model was applied to QSM images of healthy controls. The employed model demonstrated excellent generalization abilities and outperformed traditional up-sampling methods, without requiring a customized re-training. Across the three disorders investigated, it was evident that QSM is capable of distinguishing between patient groups and healthy controls while establishing correlations between imaging measurements and clinical data. These studies lay the foundation for future research, with the ultimate goal of achieving earlier and less invasive diagnoses of neurodegenerative disorders within the context of personalized medicine.

Archaeological Baltic amber: degradation mechanisms and conservation measures

The aim of this project was to achieve a deep understanding of the mechanisms by which Baltic amber degrades, in order to develop techniques for preventive conservation of archaeological amber objects belonging to the National Museum of Denmark’s collections. To examine deterioration of Baltic amber, a starting point was to identify and monitor surface and bulk properties which are affected during degradation. The way to operate consisted of the use of accelerated ageing to initiate degradation of raw Baltic amber samples in different conditions of relative humidity, oxygen exposure or pH and, successively, of the use of non/micro-destructive techniques to identify and quantify changes in visual, chemical and structural properties. A large piece of raw Baltic amber was used to prepare several test samples for two different kinds of accelerated ageing: thermal-ageing and photo-ageing. During the ageing, amber samples were regularly examined through several analytical techniques related to different information: appearance/colour change by visual examination, photography and colorimetry; chemical change by infrared spectroscopy, Raman spectroscopy and elemental analysis; rate of oxidation by oxygen measurement; qualitative analysis of released volatiles by gas chromatography – mass spectrometry. The obtained results were analysed through both critical evaluation and statistical study. After the interpretation of the achieved data, the main relations between amber and environmental factors during the degradation process became clearer and it was possible to identify the major pathways by which amber degrades, such as hydrolysis of esters into alcohols and carboxylic acids, thermal-oxidation and photo-oxidation of terpenoid components, depolymerisation and decomposition of the chemical structure. At the end it was possible to suggest a preventive conservation strategy based on the control of climatic, atmospheric and lighting parameters in the environment where Baltic amber objects are stored and displayed.

Phenotypic and genotypic characterisation of antimicrobial resistance in Escherichia coli indicator of animal, food and human origin.

This thesis presents AMR phenotypic evaluation and whole genome sequencing analysis of 288 Escherichia coli strains isolated from different sources (livestock, companion animal, wildlife, food and human) in Italy. Our data reflects general resistance trends in Europe, reporting tetracycline, ampicillin, sulfisoxazole and aminoglycosides resistance as the most common phenotypic AMR profile among livestock, pets, wildlife and humans. Identification of human and animal (livestock and companion animal) AMR profiles in niches with a rare (fishery, mollusc) or absent (vegetable, wild animal, wild boar) direct exposure to antimicrobials, suggests widespread environmental pollution with ARGs conferring resistance to these antimicrobials. Phenotypic resistance to highest priority critically important antimicrobials was mainly observed in food-producing animals and related food such as rabbit, poultry, beef and swine. Discrepancies between AMR phenotypic pattern and genetic profile were observed. In particular, phenotypic aminoglycoside, cephalosporin, meropenem, colistin resistance and ESBL profile did not have a genetic explanation in different cases. This data could suggest the diffusion of new genetic variants of ARGs, associated to these antimicrobial classes. Generally, our collection shows a virulence profile typical of extraintestinal pathogenic Escherichia coli (ExPEC) pathotype. Different pandemic and emerging ExPEC lineages were identified, in particular in poultry meat (ST10; ST23; ST69, ST117; ST131). Rabbit was suggested as a source of ST20-ST40 potential hybrid pathogens. Wildlife carried a high average number (10) of VAGs (mostly associated to ExPEC pathotype) and different predominant ExPEC lineages (ST23, ST117, ST648), suggesting its possible involvement in maintenance and diffusion of virulence determinants. In conclusion, our study provides important knowledge related to the phenotypic/genetic AMR and virulence profiles circulating in E. coli in Italy. The role of different niches in AMR dynamics has been discussed. In particular, food-producing animals are worthy of continued investigation as a source of potential zoonotic pathogens, meanwhile wildlife might contribute to VAGs spread.

Advanced neuroimaging methodologies to improve connectivity detection in normal and abnormal language brain networks

The language connectome was in-vivo investigated using multimodal non-invasive quantitative MRI. In PPA patients (n=18) recruited by the IRCCS ISNB, Bologna, cortical thickness measures showed a predominant reduction on the left hemisphere (p<0.005) with respect to matched healthy controls (HC) (n=18), and an accuracy of 86.1% in discrimination from Alzheimer’s disease patients (n=18). The left temporal and para-hippocampal gyri significantly correlated (p<0.01) with language fluency. In PPA patients (n=31) recruited by the Northwestern University Chicago, DTI measures were longitudinally evaluated (2-years follow-up) under the supervision of Prof. M. Catani, King’s College London. Significant differences with matched HC (n=27) were found, tract-localized at baseline and widespread in the follow-up. Language assessment scores correlated with arcuate (AF) and uncinate (UF) fasciculi DTI measures. In left-ischemic stroke patients (n=16) recruited by the NatBrainLab, King’s College London, language recovery was longitudinally evaluated (6-months follow-up). Using arterial spin labelling imaging a significant correlation (p<0.01) between language recovery and cerebral blood flow asymmetry, was found in the middle cerebral artery perfusion, towards the right. In HC (n=29) recruited by the DIBINEM Functional MR Unit, University of Bologna, an along-tract algorithm was developed suitable for different tractography methods, using the Laplacian operator. A higher left superior temporal gyrus and precentral operculum AF connectivity was found (Talozzi L et al., 2018), and lateralized UF projections towards the left dorsal orbital cortex. In HC (n=50) recruited in the Human Connectome Project, a new tractography-driven approach was developed for left association fibres, using a principal component analysis. The first component discriminated cortical areas typically connected by the AF, suggesting a good discrimination of cortical areas sharing a similar connectivity pattern. The evaluation of morphological, microstructural and metabolic measures could be used as in-vivo biomarkers to monitor language impairment related to neurodegeneration or as surrogate of cognitive rehabilitation/interventional treatment efficacy.

Development and validation of an echocardiography score for diagnosis of cardiac masses

Background Echocardiography is the cornerstone in the evaluation of cardiac masses and provides accurate characterization. Despite, its accuracy in diagnosis of cardiac masses (CM) remains challenging and, up to date, no validated diagnostic algorithm is validated. Purpose The aim of our study was to evaluate the diagnostic accuracy of echocardiography, to identify the echocardiographic predictors of malignancy and to develop and then validate a multiparametric echocardiographic score that could be used to estimate the likelihood of the histological nature of a CM. Materials and methods The final sample consisted of 273 consecutive patients who had a 2D-echocardiographic evaluation and a histologic diagnosis. Logistic regression was performed to evaluate the ability of echocardiographic findings to discriminate benign versus malignant masses, then a scoring system was developed and validated in a separate test cohort. Results Of the 322 patients initially included in the Bologna Cardiac Masses Registry, 13 with a poor acoustic window, 27 with no histological examination patients and 9 extra-cardiac masses were excluded. In the remaining 273 patients, classical 2-D echocardiogram identified 249 masses with a diagnostic accuracy of 88%. A weighted score [Diagnostic Echocardiographic Mass (DEM) Score] ranging from 0 to 9 was obtained from 6 variables: infiltration, polylobate mass, moderate-severe pericardial effusion. The AUC for the score was 0.965 (95% CI [0.938-0.993]). In a logistic regression analysis using the DEM score as a predictor, the likelihood of malignant CM increased more than 4 times for a 1-unit increase in the score (OR=4.468; 95% CI 2.733-7.304). A score < 3 denoted a high probability of a benign diagnosis, and a score ≥ 5 points corresponded to a higher risk of malignancy. Conclusion 2D-Echocardiography provides a high diagnostic accuracy in identifying cardiac masses and our multiparametric echocardiographic score could be useful to predict the histological nature of cardiac masses.

Design and evaluation of aerosol and liquid separation systems

Conventional chromatographic columns are packed with porous beads by the universally employed slurry-packing method. The lack of precise control of the particle size distribution, shape and position inside the column have dramatic effects on the separation efficiency. In the first part the thesis an ordered, three-dimensional, pillar-array structure was designed by a CAD software. Several columns, characterized by different fluid distributors and bed length, were produced by a stereolithographic 3D printer and compared in terms of pressure drop and height equivalent to a theroretical plate (HETP). To prevent the release of unwanted substances and to provide a surface for immobilizing a ligand, pillars were coated with one or more of the following materials: titanium dioxide, nanofibrillated cellulose (NFC) and polystyrene. The external NFC layer was functionalized with Cibacron Blue and the dynamic binding capacity of the column was measured by performing three chromatographic cycles, using bovine serum albumin (BSA) as target molecule. The second part of the thesis deals with Covid-19 pandemic related research activities. In early 2020, due to the pandemic outbreak, surgical face masks became an essential non-pharmaceutical intervention to limit the spread. To address the consequent shortage and to support the reconversion of the Italian industry, in late March 2020 a multidisciplinary group of the University of Bologna created the first Italian laboratory able to perform all the tests required for the evaluation and certification of surgical masks. More than 1200 tests were performed on about 350 prototypes, according to the standard EN 14683:2019. The results were analyzed to define the best material properties and masks composition for the production of masks with excellent efficiency. To optimize the usage of surgical masks and to reduce their environmental burden, the variation of their performance over time of usage were investigated as to determine the maximum lifetime.