'IL NOSTRO BREVE TEMPO PASSERA QUI'LUOGHI DELL'ADOLESCENZA IN VILDANDEN DI H. IBSEN, ELVEGATEN E BARNET SOM ELSKET VEIER DI C. SANDEL E IS-SLOTTET DI T. VESAAS

ABSTRACT This thesis examines the relationship between adolescent female characters, as represented in the work of three different authors from Norwegian Literature (Henrik Ibsen, Cora Sandel and Tarjei Vesaas), and the particular descriptions of the places inhabited or lands travelled by those characters. From the latter part of the 19th century and throughout the 20th century, childhood and the transition to adulthood have fascinated intellectuals, artists and people of science alike in terms of the wider perspectives offered relating to the process of formation of human identity. None more so than, adolescence \u2013 the transitional period between the reality of childhood and that of adulthood. It is a metamorphic, ever-changing period which cannot easily be defined nor labelled; it is characterised by a tumultuous display of contrasting tensions which reflect a vacillating and fermenting identity equilibrium. In short, it is a time of crisis that mirrors the radical revolution within the inner structure of the individual. It causes a heightened creative potential, precisely at a moment when new balances are being forged and refined. In this thesis it is argued that even in texts written by various authors from different periods, it is possible to discover a common tendency to portray \u201cthe places of adolescence\u201d with a similar array of symbols and motives. The landscape hosting the adolescent characters tends to display attributes which correspond to those of the characters themselves. Such places could be called isomorphic, using a notion derived from the field of Anthropological Studies. Ambiguity, paradox and a subversive drift are typical of those spaces. They are unstructured, unstable and ephemeral places that perpetually reformulate their own meaning and identity. Within them, everything is possible \u2013 every road can be discovered and taken which can lead towards the very edges of imagination. Those places embody realms of pure possibility, intimately connected to the structure of crisis which is characteristic of the adolescence years. Referring to the works of the psychoanalysts Erikson, Winnicott and Kristeva, an open and metamorphic structure has been postulated \u2013 a structure of crisis \u2013 for all the literary places where the adolescent subject is free to develop and grow in a creative way. Following Roland Barthes\u2019 theory about the Neutral as that which \u201coutplays the paradigm\u201d, the convention adopted is that such places are considered neutral - ambiguous and rebellious, something that cannot be reduced to a fixed definition. Using a category firstly introduced by Erikson regarding identity structures, other places \u2013 which at first can bear some resemblances with those of crisis \u2013 are considered rigid and close. In them no real movement is possible and all roads reveal themselves as dead ends. Analysing Vildanden (1884, The Wild Duck) by Henrik Ibsen, Elvegaten (1924, The Street On the River) and Barnet som elsket veier (1947, The Child Who Loved the Streets) by Cora Sandel and eventually Is-slottet (1963, The Ice Castle) by Tarjei Vesaas, examples of both types of landscapes are revealed, ones of creativity and growth and others of stasis and death. Referring to Ibsen\u2019s Vildanden, the analysis will focus on the hidden loft where the wild duck is kept in captivity. Although being a real space, the loft is never completely visible to the audience, a detail which triggers the spectator\u2019s and the reader\u2019s imagination. It is a place where fantasy can thrive and where new stories are free to take shape. The creative characteristics within the loft draw an association of imagery with water which holds ambiguous meanings. This place gradually reveals itself as being intimately bound to the young main character\u2019s tragic destiny. In Sandel\u2019s Elvegaten and Barnet som elsket veier isolated streets and country roads are seen to embody freedom and creativity. They contrast sharply with the busy streets of the bourgeois town, where the individual feels hemmed by social conventions and forced into a pattern which is imposed from the outside. No real inner maturation is possible there. In Tarjei Vesaas\u2019 Is-slottet two areas are particularly meaningful for the analysis in question : The ice-castle, where one of the two main characters \u2013 Unn \u2013 gets lost and dies, and the streets which accompany the other character \u2013 Siss \u2013 first into a state of confusion and isolation and then back to life. Having tailored relevant methodologies and an original theoretical framework to investigate the nature of similar literary landscapes, future extension using such convention could be applied to analyse works which describe other literary spaces that reflect different crisis points during human development

Visual stimulation activates ERK in synaptic and somatic compartments of rat cortical neurons with parallel kinetics.

BACKGROUND: Extracellular signal-regulated kinase (ERK) signalling pathway plays a crucial role in regulating diverse neuronal processes, such as cell proliferation and differentiation, and long-term synaptic plasticity. However, a detailed understanding of the action of ERK in neurons is made difficult by the lack of knowledge about its subcellular localization in response to physiological stimuli. To address this issue, we have studied the effect of visual stimulation in vivo of dark-reared rats on the spatial-temporal dynamics of ERK activation in pyramidal neurons of the visual cortex. METHODOLOGY/PRINCIPAL FINDINGS: Using immunogold electron microscopy, we show that phosphorylated ERK (pERK) is present in dendritic spines, both at synaptic and non-synaptic plasma membrane domains. Moreover, pERK is also detected in presynaptic axonal boutons forming connections with dendritic spines. Visual stimulation after dark rearing during the critical period causes a rapid increase in the number of pERK-labelled synapses in cortical layers I-II/III. This visually-induced activation of ERK at synaptic sites occurs in pre- and post-synaptic compartments and its temporal profile is identical to that of ERK activation in neuronal cell bodies. CONCLUSIONS/SIGNIFICANCE: Visual stimulation in vivo increases pERK expression at pre- and post-synaptic sites of axo-spinous junctions, suggesting that ERK plays an important role in the local modulation of synaptic function. The data presented here support a model in which pERK can have early and late actions both centrally in the cell nucleus and peripherally at synaptic contacts

PMS66 Determinants of Non-Persistence to Antiosteoporotic Drugs by Using Administrative Database

Osteoporosis treatment involves several therapeutic tools, including long-term drug therapy. Subjects with chronic disorders are more likely to be non-adherent and/or non-persistent to treatment than those with other diseases. Adherence is the extent to which patients take medication as prescribed by their physicians, whereas persistence is the time from treatment initiation to discontinuation. Lack of persistence is common among subjects using oral anti-osteoporotic drugs, and leads to increased risk of fragility fracture

Investigation of the Luco dei Marsi DSGSD revealing the first evidence of a basal shear zone in the central Apennine belt (Italy)

Deep-seated gravitational slope deformations (DSGSDs) show a wide range of geomorphological characteristics and kinematic behaviours. In many cases, deforming rock masses move on a continuous surface or a thick basal shear zone (BSZ) overlying the stable bedrock. The nature of this boundary is a significant issue in scientific debates since examples of BSZs have been observed or inferred in some DSGSDs worldwide. In the central Apennines, although several cases of DSGSDs have been described in recent decades, no evidence of BSZs has been documented thus far. This work presents the first case of a BSZ found in the region at the bottom of a large-scale gravitational deformation that affects the Mesozoic-Cenozoic carbonate ridge overhanging the Luco dei Marsi village (Abruzzi region). The BSZ consists of several metres-thick, cataclastic breccia developed within middle-Upper Cretaceous biodetritic limestone. The breccia level is exposed for approximately 200 m with a subhorizontal geometry and shows severe rock damage and weathering. The DSGSD hosting the BSZ affects an NNW-SSE-oriented and wide Miocene anticline whose eastern limb is dismembered by Pliocene-Quaternary normal faults delimiting the edge of a large Quaternary intermontane basin (the Fucino Basin). Field survey, aerial photointerpretation, and remote sensing (DInSAR technique) analyses outline an active gravity-driven process. This is characterized by several kinds of geomorphological features, including downhill- and uphill-facing scarps, ridge-top depressions, gravitational grabens and trenches in the upper and middle parts of the ridge, and bulging at the toe of the slope. These features, which can be distinguished from tectonic elements due to their shape and extension, are an indication of a high degree of internal deformation and a compound sagging geometry for the Luco dei Marsi DSGSD. The short-term activity of the process was revealed by DInSAR time series covering almost thirty years of satellite datasets, including ERS1/2, ENVISAT, COSMO-SkyMed, and SENTINEL 1 constellations. Strain rates on the order of a few mm/yr were inferred, with a marked difference between different sectors of the DSGSD area. The long-term (y > 102) lifespan of the DSGSD was framed into a multiple-step conceptual model summarizing the Early Pleistocene-Holocene geological evolution of the area. The model results outline the control exercised by extensional tectonics on DSGSD development, as progressive displacements along normal faults in the latest Pleistocene were the cause of lateral unconfinement at the toe of the slope. This work further contributes to the increasing knowledge on DSGSDs in the central Apennines and the understanding of the relationship between deformation features induced by slope morphogenesis, such as the BSZ, and Quaternary tectonics within the mountain belt

Site-specific abnormalities in the visual system of a mouse model of CDKL5 deficiency disorder

CDKL5 deficiency disorder (CDD) is a neurodevelopmental disorder characterized by a severe global developmental delay and early-onset seizures. Notably, patients show distinctive visual abnormalities often clinically diagnosed as cortical visual impairment. However, the involvement of cerebral cortical dysfunctions in the origin of the symptoms is poorly understood. CDD mouse models also display visual deficits, and cortical visual responses can be used as a robust biomarker in CDKL5 mutant mice. A deeper understanding of the circuits underlying the described visual deficits is essential for directing preclinical research and translational approaches. Here, we addressed this question in two ways: first, we performed an in-depth morphological analysis of the visual pathway, from the retina to the primary visual cortex (V1), of CDKL5 null mice. We found that the lack of CDKL5 produced no alteration in the organization of retinal circuits. Conversely, CDKL5 mutants showed reduced density and altered morphology of spines and decreased excitatory synapse marker PSD95 in the dorsal lateral geniculate nucleus and in V1. An increase in the inhibitory marker VGAT was selectively present in V1. Second, using a conditional CDKL5 knockout model, we showed that selective cortical deletion of CDKL5 from excitatory cells is sufficient to produce abnormalities of visual cortical responses, demonstrating that the normal function of cortical circuits is dependent on CDKL5. Intriguingly, these deficits were associated with morphological alterations of V1 excitatory and inhibitory synaptic contacts. In summary, this work proposes cortical circuit structure and function as a critically important target for studying CDD

Fixed Versus Free Combinations of Antihypertensive Drugs: Analyses Of Real-World Data Of Persistence With Therapy In Italy

Purpose: To analyse the pattern of use and cost of antihypertensive drugs in new users in an Italian population, and explore the patient/treatment factors associated with the risk of therapy discontinuation. Patients and methods: In this retrospective study, information was collected from a population-based electronic primary-care database. Persistence with medication use 1 year from therapy initiation was evaluated for each user using the gap method. Each new user was classified according to his/her pattern of use as: \u201ccontinuer\u201d, \u201cdiscontinuer\u201d \u201cswitching\u201d or \u201cadd-on\u201d. A Cox regression model was used to analyse the factors influencing therapy discontinuation. Primary-care costs comprised specialists\u2019 visits, diagnostic procedures and pharmacologic therapies. Results: Among 14,999 subjects included in persistence analyses, 55.1% of cases initially started on monotherapy were classified as discontinuers vs 36.5% of cases taking combination therapy (42.3% vs 32.7%, respectively, for free and fixed combinations, P < 0.01). Old age, high cardiovascular risk and being in receipt of fixed-combination therapy were associated with greater persistence. Overall, the primary-care cost/person/year of hypertension management was 3c\u20ac95.3 (IQR, 144.9). The monotherapy cost was \u20ac88 per patient (IQR, 132.9), and that for combination therapy was \u20ac151\ub1148.3. The median cost/patient with a fixed combination was lower than that for a free combination (\u20ac98.4 (IQR, 155.3) and \u20ac154.9 (IQR, 182.6), respectively). Conclusion: The initial type of therapy prescribed influences persistence. Prescribing fixed combinations might be a good choice as initial therapy

Immunohistochemical and biochemical assay of versican in human sound predentine/dentine matrix

Aim of this study was to investigate the distribution of versican proteoglycan within the human dentine organic matrix by means of a correlative immunohistochemical analysis with field emission in-lens scanning electron microscope (FEI-SEM), transmission electron microscope (TEM), fluorescence microscope (FM) and biochemical assay. Specimens containing dentine and predentine were obtained from non carious human teeth and divided in three groups: 1) FEI-SEM group: sections were exposed to a pre-embedding immunohistochemical procedure; 2) TEM group: specimens were fixed, demineralised, embedded and submitted to a post-embedding immunohistochemical procedure; 3) FM group: sections mineralised and submitted to a pre-embedding immunohistochemical procedure with fluorescence labelling. Specimens were exposed to two different antibodies to assay distribution of versican fragments and whole versican molecule. Western Blotting analysis of dentine and pulp extracts was also performed. The correlative FEI-SEM,TEM and FM analysis revealed positive immunoreaction for versican fragments both in predentine and dentine, while few gold particles identifying the whole versican molecule were found in predentine only under TEM. No labelling of versican whole molecule was detected by FEI-SEM and FM analysis. The immunoblotting analysis confirmed the morphological findings. This study suggests that in fully developed human teeth versican fragments are significant constituents of the human dentine and predentine organic matrix, while versican whole molecule can be visualised in scarce amount within predentine only. The role of versican fragments within human dentine organic matrix should be further elucidated

Cyclocreatine treatment ameliorates the cognitive, autistic and epileptic phenotype in a mouse model of Creatine Transporter Deficiency

Creatine Transporter Deficiency (CTD) is an inborn error of metabolism presenting with intellectual disability, behavioral disturbances and epilepsy. There is currently no cure for this disorder. Here, we employed novel biomarkers for monitoring brain function, together with well-established behavioral readouts for CTD mice, to longitudinally study the therapeutic efficacy of cyclocreatine (cCr) at the preclinical level. Our results show that cCr treatment is able to partially correct hemodynamic responses and EEG abnormalities, improve cognitive deficits, revert autistic-like behaviors and protect against seizures. This study provides encouraging data to support the potential therapeutic benefit of cyclocreatine or other chemically modified lipophilic analogs of Cr

Thymidylate synthase expression and genotype have no major impact on the clinical outcome of colorectal cancer patients treated with 5-fluorouracil

BACKGROUND AND OBJECTIVES: Thymidylate synthase (TS) expression levels appear to be related to response to 5-fluorouracil-(5-FU)-based chemotherapy in colorectal cancer (CRC) patients. Three polymorphisms have been proposed as modulators of TS expression: a tandemly repeated sequence (2R/3R) in the 5' UTR, a SNP (G>C) within the 3R allele and a 6bp deletion in the 3' UTR. To evaluate the influence of TS expression and polymorphisms on clinical outcome of 5-FU-treated patients we performed a comprehensive genetic analysis on 63 CRC patients. METHODS: TS expression levels were analyzed in normal and tumor tissues. TS coding sequence and UTR polymorphisms were investigated on DNA from normal tissue. LOH analysis was performed to determine tumor genotype. RESULTS: A difference in disease-free survival (DFS), although not statistically significant, was observed between high and low mRNA expression levels: patients with low levels showed longer DFS. The 2R2R genotype showed significantly lower expression than the 3R3R and 2R3R genotypes in normal tissue. No other TS polymorphism was associated with mRNA expression or clinical outcome. CONCLUSIONS: The results obtained in this pilot study indicate that the number of 5' UTR repeats is the major genetic determinant of TS expression. The lack of association with other polymorphisms might be partially explained by the existence of linkage disequilibrium in the TS gene. Our data support the growing evidence that TS control may require multiple mechanisms acting in close coordination with one another and suggest that TS genotyping alone in tumor samples is not sufficient to accurately predict response to 5-FU