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Relationship between macro and microscopic aspect of placenta and some useful parameters in the identification of critical newborn
Il tasso di mortalità neonatale varia dall'11,9% al34%, con percentuali maggiore nella prima settimana di vita.Le cause di morte neonatale sono multifattoriali. Tra tutti i parametri valutabili al parto, il punteggio APGAR, la lattaemia, la glicemia e il peso sono gli unici che possono darci un'indicazione della criticità del neonato.
Lo scopo della ricerca è stato quello di valutare parametri ematici(glicemia e lattato), parametri clinici(indice APGAR e peso alla nascita)e parametri macro/microscopici della placenta. Lo studio ha dimostrato che il punteggio APGAR e la lattatemia sono i principali parametri che consentono la tempestiva identificazione di cuccioli critici.Mentre ulteriori studi sono necessari per stabilire la relazione tra glicemia e sopravvivenza neonatale e l'identificazione di un valore soglia per l’individuazione di un neonato ipoglicemico. Interessante è la relazione emersa tra lattatemia, glicemia e peso alla nascita: neonati iperlattatemici presentano glicemie più elevate e pesi inferiori rispetto ai normolattatemici. Questo risultato sembra riflettere la maturità neonatale, infatti il basso peso alla nascita è associato ad un aumentato rischio di mortalità neonatale a causa dell'immaturità metabolica del paziente.
Ulteriori studi sono necessari per stabilire l'utilità dei parametri macro e microscopici della placenta come strumento prognostico per la sopravvivenza neonatale. Tuttavia,come osservato in altre specie, la dimensione della parte funzionale della placenta è correlata al peso del neonato. Dal punto di vista istologico i dati risultano insufficienti per determinare cosa sia normale o meno e l'impatto che le lesione placentari possano avere sulla morbilità neonatale. Un risultato importante è stata la determinazione di range di riferimento che consenta di definire un peso alla nascita normale indipendentemente dalla taglia e/o razza.Questo parametro è stato espresso come percentuale del peso alla nascita rispetto al peso materno. Infine, come già descritto nell'equino,è stata stabilita la percentuale del peso della placenta rispetto al peso alla nascita da considerarsi normale.Neonatal mortality in dogs range from 11,9% to 34%, with highest rate during the first week of life. Many factors could predispose puppies to life-threatening conditions. Among all parameters that could be evaluated at birth in order to identify neonate at risk of mortality APGAR score, lactate, glycaemia and birth weight can give us an indication of the newborn’s criticality.
The aim of this research was to evaluate blood parameters(glycaemia and lactate), clinical parameters(APGAR index and birth weight) and macro- and microscopic parameters of the placenta. The study shows that APGAR score and lactataemia are the main parameters that allow the prompt identification of critical puppies. More studies are needed to establish the relationship between glycaemia and neonatal survival,and the identification of a threshold value to identify hypoglycaemic newborn.Interesting was the relationship between lactataemia,glycaemia and birth weight:hyperlactathemic infants were found to have higher glycaemia and lower weights than normolactatemic one.This result seems to reflects newborn maturity, in fact low birth weight is associated with an increased risk of neonatal mortality due to the patient's metabolic immaturity.
Further studies are necessary to better establish the usefulness of macro- and microscopic parameters of the placenta as a prognostic tool for neonatal survival. However, as observed in other species, the size of the functional part of the placenta is correlated with the newborn weight. From the histological point of view data are insufficient to determine what is normal or not, and the impact that placenta lesion could have on neonatal morbidity.An important result was the determination of reference ranges that allow the definition of a normal birth weight regardless size and/or breed.This parameter was expressed as a percentage of birth weight to mother weight.Additionally,as already described in equine,was established the percentage of placenta weight to birth weight should have to be considered normal
Elastography Point Quantification in the evaluation of liver fibrosis in NAFLD patients
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Several non-invasive approaches to stage liver fibrosis in NAFLD patients are being developed. Elastography Point Quantification (ElastPQ) is a non-invasive method to assess liver fibrosis measuring liver stiffness.
We evaluated the diagnostic performance of ElastPQ for identifying different degrees of fibrosis in NAFLD patients. We compared ElastPQ with other non-invasive tests and identify the best liver stiffness cut offs for every fibrosis stage.
ElastPQ was performed in a training cohort of patients with biopsy-proved NAFLD, liver serum tests and Transient Elastography (TE). The diagnostic performance of ElastPQ was evaluated using AUROC and compared with TE, Fibrosis-4 score, NAFLD fibrosis score and AST/ALT. ElastPQ was performed in a validation cohort in order to validate the data.
106 patients with NAFLD were enrolled. The median stiffness values using ElastPQ was 4.69 kPa (2.82-29.86). The mean liver stiffness divided for category of fibrosis stage were: 4.18 kPa (mild fibrosis F0-1), 4.49 kPa (significant fibrosis F2), 6.89 kPa >(advanced fibrosis F3) and 12.14 kPa (cirrhosis F4). In multivariate analysis, liver stiffness was associated with the fibrosis stage (ß=2.987; p<0.001). The AUCs for the association with significant, advanced fibrosis and cirrhosis were 0.783 (95%IC 0.693-0.857), 0.855 (95%IC 0.773-
0.916) and 0.897 (95%IC 0.822-0.947), respectively. Diagnostic performance of ElastPQ compared to TE, resulted non-inferior in evaluating significant fibrosis (p=0.956), advanced fibrosis (p=0.171) and cirrhosis (p=0.773). ElastPQ had a higher diagnostic performance compared to FIB-4, NFS and AAR. The best fibrosis cuts off identified in the training cohort (80 patients enrolled) were 5.22 kPa, 6.3 kPa and 9.61 kPa respectively for fibrosis >F2, >F3 and F4. ElastPQ is a promising technique for liver fibrosis evaluatio
Automorphisms on algebraic varieties: K3 surfaces, hyperkähler manifolds, and applications on Ulrich bundles
One of the main tools to study the geometry of complex algebraic varieties is the group of automorphisms. The first part of this thesis concerns the study of symplectic automorphisms of finite order on K3 surfaces, and birational symplectic maps of finite order on projective hyperkähler manifolds which are deformation equivalent to the Hilbert scheme of K3 surfaces. In the second part of this thesis, the automorphism groups of rational homogeneous spaces are used to study Ulrich bundles in smooth projective varieties
Antibiotic stewardship in neonates: evaluation of antimicrobial exposure for suspected early onset sepsis
Background: Le early-onset sepsis (EOS) sono infezioni batteriche invasive definite dalla presenza di batteri nel sangue e/o nel liquor cefalorachidiano che esordiscono nelle prime 72 ore di vita e causano in epoca neonatale mortalità e morbilità importanti.
Scopo: Determinare l’eccesso di trattamento antibiotico (Overtreatment index=OI) nei neonati di EG ≥34 settimane con sospetta sepsi ad esordio precoce. Metodi: Tutti i nati dal 1.01.2014 al 31.12.2018 di EG ≥34 settimane presso IRCCS Azienda Ospedaliero-Universitaria e l’Ospedale Maggiore di Bologna che hanno ricevuto terapia antibiotica endovenosa nelle prime 168 ore di vita nel sospetto di EOS. Sono stati identificati 2 gruppi: EOS provata (N=7) ed EOS sospetta (N=465). Risultati: L’incidenza di EOS è stata 0.22 su 1000 nati vivi, rispettivamente 0.12/1000 per Streptococcus agalactiae (GBS) e 0.06/1000 per Escherichia coli (E.coli). L’1.75% dei neonati ha ricevuto terapia antimicrobica empirica a largo spettro. L’OI è risultato 68. L’esposizione al trattamento antibiotico nella popolazione è stata di 85 giorni/1000 nati vivi. Tra i fattori di rischio materni, il tampone vagino-rettale (TVR) e l’urinocoltura positiva sono risultati associati al rischio di EOS provata (p=.017, p =.000). I valori di proteina C reattiva (PCR) al T0, T1 e T2 tra i due gruppi sono risultati significativi (p=.000). All’analisi multivariata è stata confermata la significatività delle variabili descritte. (TVR non noto OR=15.1, 95%CI 1.98-115.50, p =.009, urinocoltura positiva OR=30.1, 95%CI 3.6-252.1, p = .002, PCR T0 OR=1.6, 95% CI 1.29-2.07, p = .000.)
Conclusioni: L’individuazione precoce di fattori di rischio e la valutazione degli indici di flogosi in neonati sintomatici può ridurre l’OI e la durata della terapia antibiotica in casi di sepsi non confermata. L’uso appropriato degli antibiotici in questa popolazione è particolarmente importante poichè riduce lo sviluppo di germi multiresistenti. Nelle Terapie Intensive Neonatali, i programmi di stewardship antimicrobica dovrebbero guidare la gestione delle sepsi.Background: Early-onset sepsis (EOS) are invasive bacterial infections defined with bacteremia or meningitis during the first 72 hours of life. Neonatal sepsis still represents an important cause of mortality and morbidity. Aim: To determine the excess of antibiotic treatment (Overtreatment index = OI) in newborns at gestation age ≥34 weeks with suspected EOS. Methods: All neonates born between 01.01.2014 and 31.12.2018 at a gestation age ≥34 weeks at IRCCS University Hospital and Maggiore Hospital of Bologna and treated with intravenous antibiotic within the first 168 hours following birth. 2 groups were identified: proven EOS (N = 7) and suspected EOS (N = 465). Results: The incidence of EOS was 0.22 for 1000 live births, respectively 0.12 / 1000 for Streptococcus agalactiae (GBS) and 0.06 / 1000 for Escherichia coli (E.coli). 1.75% of newborns received broad-spectrum empirical antimicrobial therapy. The OI was 68. The exposure to antimicrobial treatment was 85 days /1000 live births. Unknow maternal vaginal-rectal swab (VRS) and positive urine culture were associated with the risk of proven EOS (p = .017, p = .000). The differences in the C-reactive protein (CRP) values at T0, T1 and T2 between the two groups were statistically significant (p =.000). The significance of the factors described was confirmed in a multivariate logistic regression analysis. (TVR unknown OR=15.1, 95% CI 1.98-115.50, p = .009, positive urine culture OR=30.1, 95% CI 3.6-252.1, p = .002, PCR T0 OR=1.6, 95%CI 1.29-2.07, p = .000.) Conclusions: Early identification of risk factors and evaluation of early inflammatory markers in symptomatic infants reduce the OI and duration of antimicrobial therapy in unconfirmed sepsis. The rational use of antimicrobials is of paramount importance in this population because prevent the development of multi-drug resistant pathogens. In the Neonatal Intensive Care Unit setting structured antimicrobial stewardship interventions should be in place
Gender-based violence: analysis of the autopsy cases of femicide and the warnings of the Provincial Public Safety Authority for stalking and domestic violence in the metropolitan area of Bologna
Il presente lavoro tratta il tema della violenza di genere, in particolare femminicidio,
stalking e violenza domestica per la connessione tra questi intercorrente nell’escalation violenta.
Spesso, i femminicidi sono preceduti da stalking o ripetuti episodi di violenza fisica
prettamente consumata in ambito domestico e relazioni affettive pregresse/attuali.
La prima parte del lavoro descrive ambito scientifico e giuridico, internazionale e nazionale,
della violenza di genere, dimensione del fenomeno ed evoluzione
normativa a tutela delle vittime, come richiesto dalla Convenzione di Istanbul.
La seconda parte affronta aspetti medico-legali della violenza di genere (attività di patologia forense, genetica forense e tossicologia forense nei
femminicidi, assistenza medico-legale alla vittima di maltrattamenti e violenza sessuale,
valutazione medico-legale del danno alla persona per stalking).
La terza parte presenta lo studio su casistica autoptica di femminicidi del
1950-2019 e provvedimenti di ammonimento del Questore per stalking e per violenza domestica
del 2009-2020 nella provincia bolognese. Secondo i risultati il
femminicidio è un fenomeno di “vecchia data”, in un quadro normativo-culturale che “tollerava”
violenza a danno di vittime femminili. L’andamento del fenomeno è costante fino a oggi
con modifiche di cause e mezzi del decesso. L’aumentata età media delle vittime richiama il crescente fenomeno dell’elder abuse. Negli ammonimenti per
stalking e per violenza domestica analizzati prevalgono vittime
di genere femminile e autori di genere maschile, in vicende
affettive e familiari.
Lo studio approfondito delle caratteristiche di autori e vittime di femminicidio, stalking e
violenza domestica permette di individuare indicatori di rischio per implementare strategie di
prevenzione mirate. Il punto di vista privilegiato medico-legale può assumere un
ruolo centrale insieme alle altre figure coinvolte in prevenzione, repressione e contrasto
alla violenza di genere. Solo un rigoroso approccio metodologico multidisciplinare può
aiutare nella prevenzione. La ricerca in tale ambito è il punto di forza della gestione multidisciplinare
della vittima.This work talks about gender-based violence, in particular femicides,
stalking and domestic violence since the related connection in the violent escalation.
Femicides are often preceded by stalking or repeated episodes of physical violence
consumed at home and in the context of previous/actual relationships.
In the first part, the scientific and legal, international and national, fields of gender-based violence are exposed, highlighting the dimension of the phenomenon and the law's evolution protecting victims, as required by Istanbul Convention.
The second part exposes the medico-legal aspects of gender-based violence (activities of forensic pathology, forensic genetics and forensic toxicology in femicides, medico-legal assistance to the victim of physical and sexual violence, medico-legal aspect for stalking’victims).
The third part presents the study on autopsy of femicides of
1950-2019 and the warning measures of the Provincial Public Safety Authority for stalking and domestic violence of 2009-2020 in the Bologna’metropolitan area. According to our results,
femicide is a "long-standing" phenomenon, not reported in an period with no regulations for the protection of the victim. The phenomenon is constant till today, modifying causes and means of death. The increasing mean age of the victims highligt the attention
on the growing phenomenon of elder abuse. In our study, stalking and domestic violence records revealed a prevalence of female victims and male authors and a typical occurrence in love-relationship and familiar context.
The increasingly in-depth study of the characteristics of perpetrators and victims of femicide, stalking and
domestic violence allows to identify risk factors for implementing prevention-strategies. In this context, the privileged point of view of forensic medicine can have a
central role together with other figures involved in prevention, repression and contrast
of gender-based violence. Only a rigorous multidisciplinary methodological approach can help for prevention and research in this area is the strength of multidisciplinary management
of victims
"Ancestry, gender and language - The role of culture in economic development"
This thesis is a combination of research questions in development economics and economics of culture, with an emphasis on the role of ancestry, gender and language policies in shaping inequality of opportunities and socio-economic outcomes across different segments of a society. The first chapter shows both theoretically and empirically that heterogeneity in risk attitudes can be traced to the ethnic origins and ancestral way of living. In particular, I construct a measure of historical nomadism at the ethnicity level and link it to contemporary individual-level data on various proxies of risk attitudes. I exploit exogenous variation in biodiversity to build a novel instrument for nomadism: distance to domestication points. I find that descendants of ethnic groups that historically practiced nomadism (i) are more willing to take risks, (ii) value security less, and (iii) have riskier health behavior. The second chapter evaluates the nature of a trade-off between the advantages of female labor participation and the positive effects of female education. This work exploits a triple difference identification strategy relying on exogenous spike in cotton price and spatial variation in suitability for cotton, and split sample analyses based on the exogenous allocation of land contracts. Results show that gender differences in parental investments in patriarchal societies can be reinforced by the type of agricultural activity, while positive economic shocks may further exacerbate this bias, additionally crowding out higher possibilities to invest in female education. The third chapter brings novel evidence of the role of the language policy in building national sentiments, affecting educational and occupational choices. Here I focus on the case of Uzbekistan and estimate the effects of exposure to the Latin alphabet on informational literacy, education and career choices. I show that alphabet change affects people's informational literacy and the formation of certain educational and labour market trends
Surgery after biological therapy in locally advanced NSCLC with molecular driver: feasibility and effectiveness of a new multidisciplinary approach
Introduction: Surgical outcomes after biological therapy have not been investigated yet and no information about timing, postoperative complications and survival have been recorded.
Methods: This is a prospective study which compares a group of stage IIIA and IIIB NSCLC patients treated with biological therapy with patients undergoing standard induction chemotherapy.
Data reported are preliminary results on the safety and effectiveness of surgery after target therapy.
Results: We compared 22 patients treated with standard chemotherapy (Group 1) and 6 patients who received target therapy (Group 2). No differences were observed with an important bias due to the limited number of cases.
The median time of resection was 159.8 ± 62.8 for group 1 and 201 ± 57.8 for group 2 (p=0.194).
Complete resection was obtained in all Group 1-cases. Post-operative complication rate was 22% vs 16% (p=1).
Pathologists reported necrosis >50% in 13% in group 1, Fibrosis >50% was presents respectively in 27% and 33% of patients (p=1). Residual vital tumor was >50% in 77% of patients undergone CT and in 66% of patients undergone TT (p=0.622).
A total of 6 (31%) patients in the CT-group developed recurrence, 3 in the TT- group (64.2%), p was 0.634.
No difference was observed both in terms of OS (P=0.29, Figure 3) and in term of DFS (P=0.106, Figure 4).
Discussion:
There is no consensus in the use of target therapy for advanced tumor in association with surgery.
EGFR-tyrosine kinase inhibitors showed higher and more rapid response and our study wants to demonstrate that surgery after target therapy gives full access to the advantage of definitive local treatment.
In our series, despite fibrosis, radical surgery has been achieved in all patients operated. The intraoperative blood loss, operation time, postoperative hospital stay and postoperative complication rate seems to be similar
Plasticity and neuromodulation of the extended recurrent visual network
The extended visual network, which includes occipital, temporal and parietal posterior cortices, is a system characterized by an intrinsic connectivity consisting of bidirectional projections. This network is composed of feedforward and feedback projections, some hierarchically
arranged and others bypassing intermediate areas, allowing direct communication across early and late stages of processing. Notably, the early visual cortex (EVC) receives considerably more feedback and lateral inputs than feedforward thalamic afferents, placing it at the receiving
end of a complex cortical processing cascade, rather than just being the entrance stage of cortical processing of retinal input. The critical role of back-projections to visual cortices has been related to perceptual awareness, amplification of neural activity in lower order areas and improvement of stimulus processing. Recently, significant results have shown behavioural evidence suggesting the importance of reentrant projections in the human visual system, and demonstrated the feasibility of inducing their reversible modulation through a transcranial magnetic stimulation (TMS) paradigm named cortico-cortical paired associative stimulation (ccPAS). Here, a novel research line for the study of recurrent connectivity and its plasticity in the perceptual domain was put forward. In the present thesis, we used ccPAS with the aim of empowering the synaptic efficacy, and thus the connectivity, between the nodes of the visuocognitive system to evaluate the impact on behaviour. We focused on driving plasticity in specific networks entailing the elaboration of relevant social features of human faces (Chapters I & II), alongside the investigation of targeted pathways of sensory decisions (Chapter III). This allowed us to characterize perceptual outcomes which endorse the prominent role of the EVC in visual awareness, fulfilled by the activity of back-projections originating from distributed functional nodes
Simulation of photoinduced processes in organic chromophores: mapping photochemically relevant states for accurate dynamics
The simulation of ultrafast photoinduced processes is a fundamental step towards the understanding of the underlying molecular mechanism and interpretation/prediction of experimental data. Performing a computer simulation of a complex photoinduced process is only possible introducing some approximations but, in order to obtain reliable results, the need to reduce the complexity must balance with the accuracy of the model, which should include all the relevant degrees of freedom and a quantitatively correct description of the electronic states involved in the process. This work presents new computational protocols and strategies for the parameterisation of accurate models for photochemical/photophysical processes based on state-of-the-art multiconfigurational wavefunction-based methods. The required ingredients for a dynamics simulation include potential energy surfaces (PESs) as well as electronic state couplings, which must be mapped across the wide range of geometries visited during the wavepacket/trajectory propagation. The developed procedures allow to obtain solid and extended databases reducing as much as possible the computational cost, thanks to, e.g., specific tuning of the level of theory for different PES regions and/or direct calculation of only the needed components of vectorial quantities (like gradients or nonadiabatic couplings). The presented approaches were applied to three case studies (azobenzene, pyrene, visual rhodopsin), all requiring an accurate parameterisation but for different reasons. The resulting models and simulations allowed to elucidate the mechanism and time scale of the internal conversion, reproducing or even predicting new transient experiments. The general applicability of the developed protocols to systems with different peculiarities and the possibility to parameterise different types of dynamics on an equal footing (classical vs purely quantum) prove that the developed procedures are flexible enough to be tailored for each specific system, and pave the way for exact quantum dynamics with multiple degrees of freedom
Variational and learning models for image and time series inverse problems
Inverse problems are at the core of many challenging applications. Variational and learning models provide estimated solutions of inverse problems as the outcome of specific reconstruction maps. In the variational approach, the result of the reconstruction map is the solution of a regularized minimization problem encoding information on the acquisition process and prior knowledge on the solution. In the learning approach, the reconstruction map is a parametric function whose parameters are identified by solving a minimization problem depending on a large set of data. In this thesis, we go beyond this apparent dichotomy between variational and learning models and we show they can be harmoniously merged in unified hybrid frameworks preserving their main advantages. We develop several highly efficient methods based on both these model-driven and data-driven strategies, for which we provide a detailed convergence analysis. The arising algorithms are applied to solve inverse problems involving images and time series. For each task, we show the proposed schemes improve the performances of many other existing methods in terms of both computational burden and quality of the solution. In the first part, we focus on gradient-based regularized variational models which are shown to be effective for segmentation purposes and thermal and medical image enhancement. We consider gradient sparsity-promoting regularized models for which we develop different strategies to estimate the regularization strength. Furthermore, we introduce a novel gradient-based Plug-and-Play convergent scheme considering a deep learning based denoiser trained on the gradient domain. In the second part, we address the tasks of natural image deblurring, image and video super resolution microscopy and positioning time series prediction, through deep learning based methods. We boost the performances of supervised, such as trained convolutional and recurrent networks, and unsupervised deep learning strategies, such as Deep Image Prior, by penalizing the losses with handcrafted regularization terms