Neonatal outcomes following maternal SARS-CoV-2 infection in pregnancy - longitudinal follow-up and assessment of transplacental antibody transfer

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in pregnancy has been associated with multiple adverse pregnancy outcomes, including the risk of in utero mother-to-child transmission. Short- and long-term outcomes of SARS-CoV-2 exposed neonates and the extent to which maternal SARS-CoV-2 antibodies are transferred to neonates are still unclear. METHODS: Prospective observational study enrolling neonates born to mothers with SARS-CoV-2 infection in pregnancy, between April 2020-April 2021. Neonates were evaluated at birth and enrolled in a 12-month follow-up. SARS-CoV-2 IgG transplacental transfer ratio was assessed in mother-neonate dyads at birth. Maternal derived IgG were followed in infants until negativizing. RESULTS: Of 2745 neonates, 106 (3.9%) were delivered by mothers with SARS-CoV-2 infection in pregnancy. Seventy-six of 106 (71.7%) mothers were symptomatic. Median gestational age and mean birth weight were 39 weeks (range 25+5-41+4) and 3305 grams (SD 468). Six of 106 (6%) neonates were born preterm, without significant differences between asymptomatic and symptomatic mothers (P=0.67). No confirmed cases of in utero infection were detected. All infants had normal cerebral ultrasound and clinical evaluation at birth and during follow-up, until a median age of 7 months (range 5-12). All mothers and 96/106 (90.5%) neonates had detectable SARS-CoV-2 IgG at birth. Transplacental transfer ratio was higher following second trimester maternal infections (mean 0.940.46 versus 1.070.64 versus 0.750.44, P=0.039), but was not significantly different between asymptomatic and symptomatic women (P=0.20). IgG level in infants progressively decreased after birth: at 3 months 53% (51/96) and at four months 68% (63/96) had lost maternal antibodies respectively. The durability of maternal antibodies was positively correlated to the IgG level at birth (r=0.66; P<0.00001). CONCLUSIONS: Maternal SARS-CoV-2 infection was not associated with increased neonatal or long-term morbidity. No cases of confirmed in utero infection were detected. Efficient transplacental IgG transfer was found following second trimester maternal infections.

Planning and assessment techniques for spine surgeries

The rate of diagnosis and treatment of degenerative spine disorders is increasing, increasing the need for surgical intervention. Posterior spine fusion is one surgical intervention used to treat various spine degeneration pathologies To minimize the risk of complications and provide patients with positive outcomes, preoperative planning and postsurgical assessment are necessary. This PhD aimed to investigate techniques for the surgical planning and assessment of spine surgeries. Three main techniques were assessed: stereophotogrammetric motion analysis, 3D printing of complex spine deformities and finite element analysis of the thoracolumbar spine. Upon reviewing the literature on currently available spine kinematics protocol, a comprehensive motion analysis protocol to measure the multi-segmental spine motion was developed. Using this protocol, the patterns of spine motion in patients before and after posterior spine fixation was mapped. The second part investigated the use of virtual and 3D printed spine models for the surgical planning of complex spine deformity correction. Compared to usual radiographic images, the printed model allowed optimal surgical intervention, reduced surgical time and provided better surgeon-patient communication. The third part assessed the use of polyetheretherketone rods auxiliary to titanium rods to reduce the stiffness of posterior spine fusion constructs. Using a finite element model of the thoracolumbar spine, the rods system showed a decrease in the overall stress of the uppermost instrumented vertebra when compared to regular fixation approaches. Finally, a retrospective biomechanical assessment of a lumbopelvic reconstruction technique was investigated to assess the patients' gait following the surgery, the implant deformation over the years and the extent of bony fusion between spine and implant. In conclusion, this thesis highlighted the need to provide surgeons with new planning and assessment techniques to better understand postsurgical complications. The methodologies investigated in this project can be used in the future to establish a patient-specific planning protocol.

Mathematical skills: intergenerational features and relationships with cognitive and linguistic abilities

This thesis aimed to investigate the cognitive underpinnings of math skills, with particular reference to cognitive, and linguistic markers, core mechanisms of number processing and environmental variables. In particular, the issue of intergenerational transmission of math skills has been deepened, comparing parents’ and children’s basic and formal math abilities. This pattern of relationships amongst these has been considered in two different age ranges, preschool and primary school children. In the first chapter, a general introduction on mathematical skills is offered, with a description of some seminal works up to recent studies and latest findings. The first chapter concludes with a review of studies about the influence of environmental variables. In particular, a review of studies about home numeracy and intergenerational transmission is examined. The first study analyzed the relationship between mathematical skills of children attending primary school and those of their mothers. The objective of this study was to understand the influence of mothers' math abilities on those of their children. In the second study, the relationship between parents’ and children numerical processing has been examined in a sample of preschool children. The goal was to understand how mathematical skills of parents were relevant for the development of the numerical skills of children, taking into account children’s cognitive and linguistic skills as well as the role of home numeracy. The third study had the objective of investigating whether the verbal and nonverbal cognitive skills presumed to underlie arithmetic are also related to reading. Primary school children were administered measures of reading and arithmetic to understand the relationships between these two abilities and testing for possible shared cognitive markers. Finally, in the general discussion a summary of main findings across the study is presented, together with clinical and theoretical implications.

Psychobiological correlates of allostatic load

Introduction: The term Clinimetric was introduced by Feinstein in 1982, who first noticed that despite all the improvements in the assessment methods, a number of clinical phenomena were still unconsidered during the evaluation process. Yet today clinical phenomena, such as stress, relevant in diseases progression and course, are not completely evaluated. Only recently, according to the clinimetric approach, Fava and colleagues have introduced specific criteria for evaluating the allostatic overload in clinical setting. Methods: Participants were 240 blood donors recruited from May 2007 to December 2009 in 4 different blood Centers (AVIS) in Italy. Blood samples from each participant were collected for laboratory test the same day the self-rating instruments were administered (Psychosocial Index, Symptom Questionnaire, Psychological well-being scales, Temperament and Character inventory, Self-Report Altruism scale). The study explore different aspects describing sample characteristics and correlates of stress in the total sample (part I), new selection criteria applied to existing instruments to identify individuals reporting allostatic load (part II), and differences on biological correlates between subjects with vs without AL. Results: Significant differences according to gender and past illnesses have been found in different dimensions of well-being and distress. Further, distress was explained for more than 60% by 4 main factors such as anxiety, somatic symptoms, environmental mastery and persistence. According to the new criteria, 98 donors reported AL. Allostatic load individuals reported to engage in less altruistic behaviours. Also they differ in personality traits and characters from controls. In the last part, results showed significant differences among donors according to allostatic load on diverse biological parameters (RBC, MCV, immune essay). Conclusion: This study presents obvious limitations due to its preliminary nature. Further research are need to confirm that these new criteria may lead to identify high risk individuals reporting not only stressful situations but also vulnerabilities.

Trait emotional intelligence: Evidence from italian adolescents and adults

Emotional intelligence (EI) represents an attribute of contemporary attractiveness for the scientific psychology community. Of particular interest for the present thesis are the conundrum related to the representation of this construct conceptualized as a trait (i.e., trait EI), which are in turn reflected in the current lack of agreement upon its constituent elements, posing significant challenges to research and clinical progress. Trait EI is defined as an umbrella personality-alike construct reflecting emotion-related dispositions and self-perceptions. The Trait Emotional Intelligence Questionnaire (TEIQue) was chosen as main measure, given its strong theoretical and psychometrical basis, including superior predictive validity when compared to other trait EI measures. Studies 1 and 2 aimed at validating the Italian 153-items forms of the TEIQue devoted to adolescents and adults. Analyses were done to investigate the structure of the questionnaire, its internal consistencies and gender differences at the facets, factor, and global level of both versions. Despite some low reliabilities, results from Studies 1 and 2 confirm the four-factor structure of the TEIQue. Study 3 investigated the utility of trait EI in a sample of adolescents over internalizing conditions (i.e., symptoms of anxiety and depression) and academic performance (grades at math and Italian language/literacy). Beyond trait EI, concurrent effects of demographic variables, higher order personality dimensions and non-verbal cognitive ability were controlled for. Study 4a and Study 4b addressed analogue research questions, through a meta-analysis and new data in on adults. In the latter case, effects of demographics, emotion regulation strategies, and the Big Five were controlled. Overall, these studies showed the incremental utility of the TEIQue in different domains beyond relevant predictors. Analyses performed at the level of the four-TEIQue factors consistently indicated that its predictive effects were mainly due to the factor Well-Being. Findings are discussed with reference to potential implication for theory and practice.

Consumer Perception and Willingness to Pay for Local Food

A growing number of empirical studies recently investigated consumers' valuation for local food products. However, different aspects related to the local food consumption still remain vague or unexplored. As such, the objective of the present research is to fulfill the existing literature using a mixed methodological approach for the investigation of consumers' preferences and Willingness to Pay (WTP) for local food products. First of all, local food is still a blurred concept and this factor might be source of individuals' misperception for the local origin meaning. Therefore, a qualitative research has been performed in order to investigate the meaning and the perception of the local food in the Italian food market. Results from this analysis have been used as inputs for the building of a non-hypothetical Real Choice Experiment (RCE) to estimate consumers' WTP for locally and organically produced apple sauce. The contribution of this study is three-fold: (1) consumers' valuation for the local origin is interpreted in terms of regional borders, over the organic food claim in case of an unusual food product in the area of interest, (2) the interaction between individuals' personality traits and consumers’ preferences for local and organic foods is analyzed, (3) the role of Commitment Cost creation in consumers' choice making in case of uncertainty due to the use of a novel food product and of an unconventional food claim is investigated. Results suggest that consumers are willing to pay a higher price premium for organic over locally produced apple sauce, possibly because of the presence of a regulated certification. In accordance with Commitment Cost theory, the organic label might thus decrease consumers' uncertainty for the features of the product in question. Results also indicate that individuals' personality can be source of heterogeneity in consumers' preferences.

Large Eddy Simulations applied to wind loading and pollutant dispersion

The application of Computational Fluid Dynamics based on the Reynolds-Averaged Navier-Stokes equations to the simulation of bluff body aerodynamics has been thoroughly investigated in the past. Although a satisfactory accuracy can be obtained for some urban physics problems their predictive capability is limited to the mean flow properties, while the ability to accurately predict turbulent fluctuations is recognized to be of fundamental importance when dealing with wind loading and pollution dispersion problems. The need to correctly take into account the flow dynamics when such problems are faced has led researchers to move towards scale-resolving turbulence models such as Large Eddy Simulations (LES). The development and assessment of LES as a tool for the analysis of these problems is nowadays an active research field and represents a demanding engineering challenge. This research work has two objectives. The first one is focused on wind loads assessment and aims to study the capabilities of LES in reproducing wind load effects in terms of internal forces on structural members. This differs from the majority of the existing research, where performance of LES is evaluated only in terms of surface pressures, and is done with a view of adopting LES as a complementary design tools alongside wind tunnel tests. The second objective is the study of LES capabilities in calculating pollutant dispersion in the built environment. The validation of LES in this field is considered to be of the utmost importance in order to conceive healthier and more sustainable cities. In order to validate the numerical setup adopted, a systematic comparison between numerical and experimental data is performed. The obtained results are intended to be used in the drafting of best practice guidelines for the application of LES in the urban physics field with a particular attention to wind load assessment and pollution dispersion problems.

Advanced solutions for authenticity and quality of virgin olive oils

This Ph.D. project aimed to the development and improvement of analytical solutions for control of quality and authenticity of virgin olive oils. According to this main objective, different research activities were carried out: concerning the quality control of olive oil, two of the official parameters defined by regulations (free acidity and fatty acid ethyl esters) were taken into account, and more sustainable and easier analytical solutions were developed and validated in-house. Regarding authenticity, two different issues were faced: verification of the geographical origin of extra virgin (EVOOs) and virgin olive oils (VOOs), and assessment of soft-deodorized oils illegally mixed with EVOOs. About fatty acid ethyl esters, a revised method based on the application of off-line HPLC-GC-FID (with PTV injector), revising both the preparative phase and the GC injector required in the official method, was developed. Next, the method was in-house validated evaluating several parameters. Concerning free acidity, a portable system suitable for in-situ measurements of VOO free acidity was developed and in-house validated. Its working principle is based on the estimation of the olive oil free acidity by measuring the conductance of an emulsion between a hydro-alcoholic solution and the sample to be tested. The procedure is very quick and easy and, therefore, suitable for people without specific training. Another study developed during the Ph.D. was about the application of flash gas chromatography for volatile compounds analysis, combined with untargeted chemometric data elaborations, for discrimination of EVOOs and VOOs of different geographical origin. A set of 210 samples coming from different EU member states and extra-EU countries were collected and analyzed. Data were elaborated applying two different classification techniques, one linear (PLS-DA) and one non-linear (ANN). Finally, a preliminary study about the application of GC-IMS (Gas Chromatograph - Ion Mobility Spectrometer) for assessment of soft-deodorized olive oils was carried out.

Deciphering the role of plant microbiome on strawberry and raspberry growth, resistance, fruit quality and aroma

Besides their own adaptation strategies, plants might exploit microbial symbionts for overcoming both biotic and abiotic stresses and increase fitness. The current scenario of rapid climate change is demanding more sustainable agricultural management practices. The application of microbe-based products as a valid alternative to synthetic pesticides and fertilizers and their use to overcome stresses exacerbated by climate change, have been reviewed in the first part of this thesis. Berry fruits are widely cultivated and appreciated for their aromatic and nutraceutical properties. This thesis is focused on the role of plant and fruit microbiome on strawberry and raspberry growth, resistance, fruit quality and aroma. A taxonomical and functional description of the microbiome of different organs of three strawberry genotypes was performed both by traditional cultural dependent method and Next Generation Sequencing technique, highlighting a significant role of plant organs and genotype in determining the composition of microbial communities. Additionally, a selection of bacteria native of strawberry plants were isolated and screened for their plant growth promoting abilities and tested under the biotic stress of Xanthomonas fragariae infection and the abiotic stress of induced salinity. The monitoring of biometric parameters allowed the selection of a more restricted panel of bacterial strains, whose beneficial potential was tested in coordinated inoculations, or singularly. Raspberry plant was used for investigating the effect of cultivation method in determining fruit microbiome, and its consequent influence of berry quality and aroma. Interestingly, the cultivation method strongly influenced fruit nutraceutical traits, aroma and epiphytic bacterial biocoenosis. The involvement of the bacterial microbiota in fruit aroma determination was evaluated by performing GC–MS analysis of VOCs occurring in control, sterile and artificially reinoculated berries and by characterizing control and reinoculated berry microbiome. Differently treated berries showed significantly different aromatic profile, confirming the role of bacteria in fruit aroma development.

[In search of] Digital biomarkers for objective pain assessment

Pain is a highly complex phenomenon involving intricate neural systems, whose interactions with other physiological mechanisms are not fully understood. Standard pain assessment methods, relying on verbal communication, often fail to provide reliable and accurate information, which poses a critical challenge in the clinical context. In the era of ubiquitous and inexpensive physiological monitoring, coupled with the advancement of artificial intelligence, these new tools appear as the natural candidates to be tested to address such a challenge. This thesis aims to conduct experimental research to develop digital biomarkers for pain assessment. After providing an overview of the state-of-the-art regarding pain neurophysiology and assessment tools, methods for appropriately conditioning physiological signals and controlling confounding factors are presented. The thesis focuses on three different pain conditions: cancer pain, chronic low back pain, and pain experienced by patients undergoing neurorehabilitation. The approach presented in this thesis has shown promise, but further studies are needed to confirm and strengthen these results. Prior to developing any models, a preliminary signal quality check is essential, along with the inclusion of personal and health information in the models to limit their confounding effects. A multimodal approach is preferred for better performance, although unimodal analysis has revealed interesting aspects of the pain experience. This approach can enrich the routine clinical pain assessment procedure by enabling pain to be monitored when and where it is actually experienced, and without the involvement of explicit communication,. This would improve the characterization of the pain experience, aid in antalgic therapy personalization, and bring timely relief, with the ultimate goal of improving the quality of life of patients suffering from pain.

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.