A Novel Flexible and Steerable Probe for Minimally Invasive Soft Tissue Intervention

Current trends in surgical intervention favour a minimally invasive (MI) approach, in which complex procedures are performed through increasingly small incisions. Specifically, in neurosurgery, there is a need for minimally invasive keyhole access, which conflicts with the lack of maneuverability of conventional rigid instruments. In an attempt to address this fundamental shortcoming, this thesis describes the concept design, implementation and experimental validation of a novel flexible and steerable probe, named “STING” (Soft Tissue Intervention and Neurosurgical Guide), which is able to steer along curvilinear trajectories within a compliant medium. The underlying mechanism of motion of the flexible probe, based on the reciprocal movement of interlocked probe segments, is biologically inspired and was designed around the unique features of the ovipositor of certain parasitic wasps. Such insects are able to lay eggs by penetrating different kinds of “host” (e.g. wood, larva) with a very thin and flexible multi-part channel, thanks to a micro-toothed surface topography, coupled with a reciprocating “push and pull” motion of each segment. This thesis starts by exploring these foundations, where the “microtexturing” of the surface of a rigid probe prototype is shown to facilitate probe insertion into soft tissue (porcine brain), while gaining tissue purchase when the probe is tensioned outwards. Based on these findings, forward motion into soft tissue via a reciprocating mechanism is then demonstrated through a focused set of experimental trials in gelatine and agar gel. A flexible probe prototype (10 mm diameter), composed of four interconnected segments, is then presented and shown to be able to steer in a brain-like material along multiple curvilinear trajectories on a plane. The geometry and certain key features of the probe are optimised through finite element models, and a suitable actuation strategy is proposed, where the approach vector of the tip is found to be a function of the offset between interlocked segments. This concept of a “programmable bevel”, which enables the steering angle to be chosen with virtually infinite resolution, represents a world-first in percutaneous soft tissue surgery. The thesis concludes with a description of the integration and validation of a fully functional prototype within a larger neurosurgical robotic suite (EU FP7 ROBOCAST), which is followed by a summary of the corresponding implications for future work

Exploring morphodynamic co-benefits of salt-marsh restoration

openThe Venice Lagoon possesses one of the planet's most fascinating and distinctive ecosystems, owing to its unique geographical location. Situated in the northern reaches of the Adriatic Sea, this natural lagoon has undergone significant human-induced changes over time to accommodate various activities. Originally characterized by shallow waters, resulting from limited erosion from the sea and significant sediment deposition from major rivers such as the Piave, Sile, Brenta, and Bacchiglione, human intervention in past centuries diverted these primary waterways and excavated channels to deepen the lagoon for navigation purposes. In addition, land reclamation efforts were initiated to convert salt marshes (i.e., low-lying vegetated wetlands periodically flooded by tides) into agricultural, residential, or aquacultural land. Salt marshes are a defining feature not only of the Venice Lagoon but also of many low-lying temperate and subtropical coastal regions. Currently, extensive loss of salt marshes is occurring worldwide, and significant efforts are underway to conserve and restore these valuable ecosystems, along with the services they provide to the environment and society, such as blue- carbon sequestration, environmental remediation, shoreline protection, and habitat provision. While it is undeniably valuable to restore salt marshes for ecological and economic reasons, most previous studies have not closely examined the co-benefits of marsh restoration on coastal system morphodynamic evolution. In particular, it remains unclear whether marsh restoration can return the system to the conditions observed before marshes were degraded. The Venice Lagoon provides a unique opportunity to study this issue in detail, given its extensive historical data and state-of-the-art numerical modeling techniques that enable the reconstruction of past, present, and future lagoon morphologies. We can investigate the effects of marsh degradation and the potential impacts of future restoration projects at the scale of the entire tidal basin. In this study, I used numerical modeling techniques to examine the hydrodynamic and sediment transport processes in three different configurations of the Venice Lagoon: the present one and those observed in 1932 and 1901. These two historical configurations serve as references to simulate the effects of marsh restoration projects aimed at restoring the total marsh area that existed at those times. The research I conducted demonstrates that even extensive marsh restoration alone will not suffice in fully returning the Venice Lagoon's hydro-morphodynamics to those observed at the beginning of the last century. This is because not only have salt marshes changed, but the overall lagoon morphology has also evolved, making marsh restoration projects essentially neutral with respect to current hydrodynamic and sediment transport processes within the lagoon. While not diminishing the intrinsic significance of marsh restoration projects, the findings of this study specifically illustrate that marsh restoration may not provide a practical solution to address the long-standing issue of morphological degradation observed in Venice over the past century, also urging caution in considering the restoration of similar shallow-water back-barrier lagoons that are prevalent along coastlines worldwide.The Venice Lagoon possesses one of the planet's most fascinating and distinctive ecosystems, owing to its unique geographical location. Situated in the northern reaches of the Adriatic Sea, this natural lagoon has undergone significant human-induced changes over time to accommodate various activities. Originally characterized by shallow waters, resulting from limited erosion from the sea and significant sediment deposition from major rivers such as the Piave, Sile, Brenta, and Bacchiglione, human intervention in past centuries diverted these primary waterways and excavated channels to deepen the lagoon for navigation purposes. In addition, land reclamation efforts were initiated to convert salt marshes (i.e., low-lying vegetated wetlands periodically flooded by tides) into agricultural, residential, or aquacultural land. Salt marshes are a defining feature not only of the Venice Lagoon but also of many low-lying temperate and subtropical coastal regions. Currently, extensive loss of salt marshes is occurring worldwide, and significant efforts are underway to conserve and restore these valuable ecosystems, along with the services they provide to the environment and society, such as blue- carbon sequestration, environmental remediation, shoreline protection, and habitat provision. While it is undeniably valuable to restore salt marshes for ecological and economic reasons, most previous studies have not closely examined the co-benefits of marsh restoration on coastal system morphodynamic evolution. In particular, it remains unclear whether marsh restoration can return the system to the conditions observed before marshes were degraded. The Venice Lagoon provides a unique opportunity to study this issue in detail, given its extensive historical data and state-of-the-art numerical modeling techniques that enable the reconstruction of past, present, and future lagoon morphologies. We can investigate the effects of marsh degradation and the potential impacts of future restoration projects at the scale of the entire tidal basin. In this study, I used numerical modeling techniques to examine the hydrodynamic and sediment transport processes in three different configurations of the Venice Lagoon: the present one and those observed in 1932 and 1901. These two historical configurations serve as references to simulate the effects of marsh restoration projects aimed at restoring the total marsh area that existed at those times. The research I conducted demonstrates that even extensive marsh restoration alone will not suffice in fully returning the Venice Lagoon's hydro-morphodynamics to those observed at the beginning of the last century. This is because not only have salt marshes changed, but the overall lagoon morphology has also evolved, making marsh restoration projects essentially neutral with respect to current hydrodynamic and sediment transport processes within the lagoon. While not diminishing the intrinsic significance of marsh restoration projects, the findings of this study specifically illustrate that marsh restoration may not provide a practical solution to address the long-standing issue of morphological degradation observed in Venice over the past century, also urging caution in considering the restoration of similar shallow-water back-barrier lagoons that are prevalent along coastlines worldwide

Focusing and orienting spatial attention differently modulate crowding in central and peripheral vision

The allocation of attentional resources to a particular location or object in space involves two distinct processes: an orienting process and a focusing process. Indeed, it has been demonstrated that performance of different visual tasks can be improved when a cue, such as a dot, anticipates the position of the target (orienting), or when its dimensions (as in the case of a small square) inform about the size of the attentional window (focusing). Here, we examine the role of these two components of visuo-spatial attention (orienting and focusing) in modulating crowding in peripheral (Experiment 1 and Experiment 3a) and foveal (Experiment 2 and Experiment 3b) vision. The task required to discriminate the orientation of a target letter "T,'' close to acuity threshold, presented with left and right "H'' flankers, as a function of target-flanker distance. Three cue types have been used: a red dot, a small square, and a big square. In peripheral vision (Experiment 1 and Experiment 3a), we found a significant improvement with the red dot and no advantage when a small square was used as a cue. In central vision (Experiment 2 and Experiment 3b), only the small square significantly improved participants' performance, reducing the critical distance needed to recover target identification. Taken together, the results indicate a behavioral dissociation of orienting and focusing attention in their capability of modulating crowding. In particular, we confirmed that orientation of attention can modulate crowding in visual periphery, while we found that focal attention can modulate foveal crowdin

Serotype epidemiology and multidrug resistance patterns of Salmonella enterica infecting humans in Italy

BACKGROUND: Salmonella enterica is the zoonotic agent most frequently responsible for foodborne infections in humans worldwide. In this work the presence of S. enterica was investigated in 734 unique enteropathogenic isolates collected from human patients between 2011 and 2012. RESULTS: All Salmonella spp. isolates were subjected to serotyping and antimicrobial susceptibility testing. Isolates displaying phenotypes and antimicrobial susceptibility profiles different from the reference strains were genotipically characterized. Several plasmid-embedded resistance determinants were identified and characterized. Non-typhoidal serotypes were most frequently diagnosed; monophasic Salmonella typhimurium 1,4 [5],12:i- and S. typhimurium represented the most prevalent serovars. Five isolates displayed phenotypes with extremely reduced susceptibility to antimicrobials: we detected multidrug resistance elements belonging to Ambler class A and class C in two non-typhoidal S. enterica serovars, i.e. Rissen and monophasic S. typhimurium 1,4 [5],12:i-, and in one typhoidal serovar, i.e., Paratyphi B. These resistance determinants have been so far almost exclusively associated with non-Salmonella members of the Enterobacteriaceae family. Alarmingly, two colistin resistant Salmonella enteritidis were also found. CONCLUSIONS: This work draws the attention to the still low, but rising, percentage of multidrug resistant Salmonella isolates infecting humans in Italy. Our results suggest that prompt monitoring of Salmonella serovar dissemination and resistance to antimicrobials is highly required

Non-canonical proteolytic activation of human prothrombin by subtilisin from Bacillus subtilis may shift the procoagulant\ue2\u80\u93anticoagulant equilibrium toward thrombosis

Blood coagulation is a finely regulated physiological process culminating with the factor Xa (FXa)-mediated conversion of the prothrombin (ProT) zymogen to active -thrombin (T). In the prothrombinase complex on the platelet surface, FXa cleaves ProT at Arg-271, generating the inactive precursor pre-thrombin-2 (Pre2), which is further attacked at Arg-320 \u2013Ile-321 to yield mature T. Whereas the mechanism of physiological ProT activation has been elucidated in great detail, little is known about the role of bacterial proteases, possibly released in the bloodstream during infection, in inducing blood coagulation by direct proteolytic ProT activation. This knowledge gap is particularly concerning, as bacterial infections are frequently complicated by severe coagulopathies. Here, we show that addition of subtilisin (50 nM to 2 M), a serine protease secreted by the non-pathogenic bacterium Bacillus subtilis, induces plasma clotting by proteolytically converting ProT into active Pre2, a nicked Pre2 derivative with a single cleaved Ala-470 \u2013Asn-471 bond. Notably, we found that this non-canonical cleavage at Ala-470 \u2013Asn-471 is instrumental for the onset of catalysis in Pre2, which was, however, reduced about 100 \u2013200-fold compared with T. Of note, Pre2 could generate fibrin clots from fibrinogen, either in solution or in blood plasma, and could aggregate human platelets, either isolated or in whole blood. Our findings demonstrate that alternative cleavage of ProT by proteases, even by those secreted by non-virulent bacteria such as B. subtilis, can shift the delicate procoagulant\u2013anticoagulant equilibrium toward thrombosis

Simplification or complexification : auxiliary selection and anti-agreement effect in Brazilian Venetan

In this paper we discuss a change in the auxiliary selectional pattern of Brazilian Venetan, a heritage Italo-Romance variety spoken in southern Brazil. Venetan varieties display a default form of the past participle in constructions with postverbal subjects and a fully agreeing form in constructions with preverbal subjects: this is true both for the homeland varieties of the language, spoken in northern Italy, as well as for the heritage variety under analysis in this paper, spoken in southern Brazil. A crucial difference emerges in unaccusative constructions: while Italian Venetan uses the same form of the auxiliary BE in presence of preverbal and postverbal subjects, Brazilian Venetan uses a specialized form of the auxiliary in the constructions with default agreement on the past participle, when postverbal subjects are present. We argue that the specialized auxiliary form emerges as a necessary resumption in the case of lack of agreement. The heritage variety becomes, therefore, morphosyntactically more complex than the non-heritage counterpart.En aquest article analitzem un canvi en el patró de selecció de l'auxiliar del vènet brasiler, una varietat d'herència italo-romànica parlada al sud del Brasil. Les varietats vènetes mostren una forma predeterminada del participi passat en construccions amb subjectes postverbals i una forma totalment concordada en construccions amb subjectes preverbals: això és cert tant per a les varietats de la llengua nativa, parlades al nord d'Itàlia, com per a la varietat d'herència parlada al sud del Brasil que s'analitza en aquest article. En les construccions inacusatives es produeix una diferència crucial: mentre que el vènet italià fa servir la mateixa forma de l'auxiliar 'ser' en presència de subjectes preverbals i postverbals, el vènet brasiler fa servir una forma especialitzada de l'auxiliar en les construccions amb concordança per defecte del participi passat, amb subjectes postverbals. Argumentem que la forma auxiliar especialitzada sorgeix com una represa necessària en cas de manca de concordança La varietat d'herència esdevé, doncs, morfosintàcticament més complexa que la variant nativa

Otoacoustic emissions and medial olivocochlear system: patients with tinnitus and no hearing loss

BACKGROUND: tinnitus. AIM: to compare the results of otoacoustic emissions for transitory stimulus (TEOAE) and the functioning of the olivocochlear medial system, in individuals with normal hearing sensibility, with and without tinnitus. METHOD: participants of this study were 60 subjects, with tonal thresholds and acoustic imitance measurements within normal standards, distributed in two groups: group one - 30 subjects with tinnitus and group two - 30 subjects without tinnitus, paired up by gender and age. Both groups were submitted to the TEOAE test, with and without the presence of white contralateral white noise at 60dB NPS. For the 19 subjects who presented unilateral tinnitus, TEOAE and suppression results were compared regarding the variables of side, taking in consideration the presence of tinnitus. RESULTS: in the group comparison, with and without tinnitus, there was no significant statistical difference for the incidence of TEOAE, response levels, and incidence of the suppression effect. Significant statistical difference was not observed between the right and left ears in the group with tinnitus. For the 19 subjects with unilateral tinnitus, a higher amplitude of the responses and a higher suppression incidence were observed for the right ear, as well as a higher incidence of tinnitus and a lower incidence of suppression for the left ear. CONCLUSION: there was no significant statistical difference for both TEOAE incidence and response levels, as well as for the functioning of the olivocochlear medial system between the subjects, with normal hearing sensibility, with and without tinnitus. For the subjects who presented unilateral tinnitus, the overall TEOAE reponse levels was significantly higher in the ear with no tinnitus and the olivocochlear medial system was significantly less efficient in the ear with tinnitus.TEMA: zumbido. OBJETIVO: comparar os resultados das emissões otoacústicas transitório por estímulo (EOAT) e do funcionamento do sistema olivococlear medial, em indivíduos com sensibilidade auditiva normal, com e sem zumbido. MÉTODO: a casuística deste estudo foi composta por 60 sujeitos, com limiares tonais e medidas da imitância acústica dentro dos padrões da normalidade distribuídos em dois grupos: grupo um formado por 30 sujeitos com zumbido e grupo dois por 30 sujeitos sem zumbido, pareados por gênero e idade. Os dois grupos foram submetidos ao teste das EOAT com e sem ruído branco contralateral a 60dB NPS. Em 19 sujeitos que apresentavam zumbido unilateral comparou-se os resultados das EOAT e supressão em relação à variável lado, considerando-se o lado do zumbido. RESULTADOS: na comparação entre os grupos com e sem zumbido não houve diferença estatisticamente significante quanto à ocorrência das EOAT, à amplitude de resposta, e à ocorrência do efeito de supressão. Não se observou diferença estatisticamente significante entre as orelhas direita (OD) e esquerda (OE) no grupo com zumbido. Nos 19 sujeitos com zumbido unilateral, observou-se maior amplitude de resposta e maior ocorrência de supressão à direita e maior ocorrência de zumbido e menor ocorrência de supressão à esquerda. CONCLUSÃO: não houve diferença estatisticamente significante tanto na ocorrência e amplitude de respostas das EOAT quanto no funcionamento do sistema olivococlear medial entre os sujeitos, com sensibilidade auditiva normal, com e sem zumbido. Nos sujeitos que apresentaram zumbido unilateral, observou-se que a amplitude geral das EOAT foi maior na orelha sem zumbido e que o sistema olivococlear medial foi menos eficiente na orelha com zumbido de forma estatisticamente significante.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaAudiologia do Centro de Especialização em Fonoaudiologia ClínicaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de Otorrinolaringologia e Distúrbios da Comunicação HumanaUNIFESP, EPM, Depto. de Otorrinolaringologia e Distúrbios da Comunicação HumanaSciEL

Classification and Regression of Learner’s Scores in Logic Environment

This paper presents the possibility of classifying and regressing learner’s scores according to different cognitive tasks which are grouped with difficulty level, type and category. This environment is namely, Logic environment. It is mainly divided into three main categories: memory, concentration and reasoning. To classify and regress learner’s scores according to the category and the type of cognitive task acquired, we trained and tested different machine learning algorithms such as linear regression, support vector machines, random forests and gradient boosting. Primary results shows that a random forest algorithm is the most suitable model for classifying and regressing the learners’ scores in cognitive tasks, where the features most important for the model are, in descending order: the task difficulty and the task category in the case of regression, the task difficulty, the time taken by the participant before completing it, and his electroencephalogram mental metrics in the case of classification

LewiSpace: an Exploratory Study with a Machine Learning Model in an Educational Game

The use of educational games as a tool for providing learners with a playful and educational aspect is widespread. In this paper, we present an educational game that we developed to teach a chemistry lesson, namely drawing a Lewis diagram. Our game is a 3D environment known as LewiSpace and aims at balancing between playful and educational contents in order to increase engagement and motivation while learning. The game contains mainly five different missions aim at constructing Lewis diagram molecules which are organized in an ascending order of difficulty. We also conducted an experiment to gather data about learners’ cognitive and emotional states as well as their behaviours through our game by using three types of sensors (electroencephalography, eye tracking, and facial expression recognition with an optical camera) and a self report personality questionnaire (the Big Five). Primary results show that a machine learning model namely logistic regression, can predict with some success whether the learner will success or fail in each mission of our game, and paves the way for an adaptive version of the game. This latter will challenge or assist learners based on some features extracted from our data. Feature extraction integrated into a machine learning model aims mainly at providing learners’ with a real-time adaptation according to their performance and skills while progressing in our game