Speed-accuracy strategy regulations in prefrontal tumor patients

The ability to flexibly switch between fast and accurate decisions is crucial in everyday life. Recent neuroimaging evidence suggested that left lateral prefrontal cortex plays a role in switching from a quick response strategy to an accurate one. However, the causal role of the left prefrontal cortex in this particular, non-verbal, strategy switch has never been demonstrated. To fill this gap, we administered a perceptual decision-making task to neuro-oncological prefrontal patients, in which the requirement to be quick or accurate changed randomly on a trial-by-trial basis. To directly assess hemispheric asymmetries in speed-accuracy regulation, patients were tested a few days before and a few days after surgical excision of a brain tumor involving either the left (N=13) or the right (N=12) lateral frontal brain region. A group of age- and education-matched healthy controls was also recruited. To gain more insight on the component processes implied in the task, performance data (accuracy and speed) were not only analyzed separately but also submitted to a diffusion model analysis. The main findings indicated that the left prefrontal patients were impaired in appropriately adopting stricter response criteria in speed-to-accuracy switching trials with respect to healthy controls and right prefrontal patients, who were not impaired in this condition. This study demonstrates that the prefrontal cortex in the left hemisphere is necessary for flexible behavioral regulations, in particular when setting stricter response criteria is required in order to successfully switch from a speedy strategy to an accurate one

Refractoriness within the semantic system: investigations on the access and the content of semantic memory

The starting purpose of this project was to investigate some issues related to the mechanisms underlying the efficient access to concepts within the semantic memory systems. These issues were mainly related to the role of refractoriness in explaining the comprehension deficits underlying semantic access. The insights derived from this first approach were then used to formulate and test hypotheses about the organization of the contents of the semantic system itself. The first part of the thesis presents an investigation of the semantic abilities of an unselected case-series of patients affected by tumours to either the left or right temporal lobes in order to detect possible semantic access difficulties. Semantic access deficits are typically attributed to the semantic system becoming temporarily refractory to repeated activation. Previous investigations on the topic were mainly based on single case reports, mainly on stroke patients. The rare examples of group studies suggested moreover the possibility that the syndrome might not be functionally unitary. The tasks used in the study were two word-to-picture matching tasks aimed to control for the typical variables held to be able to distinguish semantic access from degradation syndromes (consistency of access, semantic relatedness, word frequency, presentation rate and serial position). In the group of tumour patients tested access deficits were consistently found in patients with high grade tumours in the left posterior superior temporal lobe. However, the patients were overall only weakly affected by the typical temporal factors (presentation rate and serial position) characterizing an access syndrome as refractory. The pattern of deficit, together with the localization data, suggested that the deficit described is qualitatively different from typical semantic access syndromes and possibly caused by the disconnection of posterior temporal lexical input areas from the semantic system. In the second study we tried to answer the question whether semantic access deficits are caused by the co-occurrence of two causes (refractoriness and a lexicalsemantic disconnection) or whether the presence of refractoriness in itself is sufficient to induce all the behavioural effects described in access syndromes. A second aim of the study was moreover to investigate the precise locus of refractory behaviour, since refractory effects have also been reported in naming tasks in which the possibility exists that the interference might be located at a post-semantic lexical stage of processing. To address these issues a series of three behavioural experiments on healthy subjects was conducted. The tasks used were speeded versions of the same word-to picture matching tasks used in the previous study. A speeded paradigm was adopted in order to induce a mild refractory state also in healthy participants. The results showed that it was possible to induce, in the group of subjects tested, a performance similar to that of refractory semantic access patients. Since no post-semantic stage of processing is assumed to be necessary to perform these tasks it was argued that refractoriness arises due to interference occurring between representations within the semantic system itself. In the second part of the project, the finding that refractoriness arises due to interference involving semantic representations themselves, was used to investigate issues related to the organization of the content within the semantic memory. In particular, a second series of behavioural experiments was performed to investigate whether the way an object is manipulated is indeed a feature that defines manipulable objects at a semantic level. The tasks used were speeded word-to-picture matching tasks similar to those previously described. A significantly greater interference was found in the recognition of objects sharing similar manipulation than in the recognition of objects sharing only visual similarity. Moreover the repeated presentation of objects with similar manipulation created a \u2018negative\u2019 serial position effect (with error increasing over presentations), while the repeated presentation of objects sharing only visual similarity created an opposite \u2018positive\u2019 serial position effect (learning). The role of manipulability in the semantic representation of manipulable objects was further investigated in the last study of this work. In a second unselected group of brain tumour patients the ability to name living things and artifacts was investigated. Artifacts were manipulable objects, varying in the degree of their manipulability. Results from both behavioural and Voxel-based Lesion Symptom Mapping (VLSM) analyses showed that the only patients showing a selective deficit in naming artifacts (particularly highly manipulable objects) were patients with lesions in the posterior middle and superior portions of the left temporal lobe, an area lying within the basin of those regions involved in processing object-directed actions and previously linked to the processing of manipulable objects in a wide range of studies. The results of these last two studies support \u2018property-based networks\u2019 accounts of semantic knowledge rather than \u2018undifferentiated network\u2019 accounts. Overall this series of studies represents an attempt to better understand the mechanisms that underlie the access to semantic representations and, indirectly, the structure of representations stored within semantic networks. The insights obtained about the mechanisms of access to stored semantic representations were used as a tool to investigate the structures of the same semantic representations. A combination of different approaches was used (from behavioural speeded interference paradigms on healthy subjects, to neuropsychological case series investigations, as well as Voxel-based Lesion Symptom Mapping technique), to \u2018cross-validate\u2019 the results obtained at any level of analysis

Augev Method and an Innovative Use of Vocal Spectroscopy in Evaluating and Monitoring the Rehabilitation Path of Subjects Showing Severe Communication Pathologies

A strongly connotative element of developmental disorders (DS) is the total or partial impairment of verbal communication and, more generally, of social interaction. The method of Vocal-verb self-management (Augev) is a systemic organicistic method able to intervene in problems regarding verbal, spoken and written language development successfully. This study intends to demonstrate that it is possible to objectify these progresses through a spectrographic examination of vocal signals, which detects voice phonetic-acoustic parameters. This survey allows an objective evaluation of how effective an educational-rehabilitation intervention is. This study was performed on a population of 40 subjects (34 males and 6 females) diagnosed with developmental disorders (DS), specifically with a diagnosis of the autism spectrum disorders according to the DSM-5. The 40 subjects were treated in “la Comunicazione” centers, whose headquarters are near Bari, Brindisi and Rome. The results demonstrate a statistical significance in a correlation among the observed variables: supervisory status, attention, general dynamic coordination, understanding and execution of orders, performing simple unshielded rhythmic beats, word rhythm, oral praxies, phono-articulatory praxies, pronunciation of vowels, execution of graphemes, visual perception, acoustic perception, proprioceptive sensitivity, selective attention, short-term memory, segmental coordination, performance of simple rhythmic beatings, word rhythm, voice setting, intonation of sounds within a fifth, vowel pronunciation, consonant pronunciation, graphematic decoding, syllabic decoding, pronunciation of caudate syllables, coding of final syllable consonant, lexical decoding, phoneme-grapheme conversion, homographic grapheme decoding, homogeneous grapheme decoding, graphic stroke

virtual maintenance simulation for socially sustainable serviceability

Abstract In order to achieve more sustainable development processes, industries need not only to improve energy efficiency and reduce costs, but also to increase the operators' wellbeing to promote social sustainability. In this context, the present research focuses on the definition of a methodology based on human-centred virtual simulation to improve the social sustainability of maintenance tasks by enhancing system design and improving its serviceability. It is based on the operators' involvement and the analysis of their needs from the early design stages on virtual mock-ups. The methodology proposed merges a protocol analysis for human factors assessment and an immersive virtual simulation where immersive serviceability simulations can be used during design phases. To demonstrate the effectiveness of the proposed method, an industrial use case has been carried out in collaboration with CNH Industrial

a mixed reality digital set up to support design for serviceability

Abstract Design for serviceability begins with understanding the customer needs related to availability, reliability, accessibility and visibility, and aims at designing optimized systems where maintenance operations are easy and intuitive in order to reduce the time to repair and service costs. However, service actions are difficult to predict in front of a traditional CAD model. In this context, digital manufacturing tools and virtual simulation technologies can be validly used to create mixed digital environments where service tasks can be simulated in advance to support product design and improve maintenance actions. Furthermore, the use of human monitoring sensors can be used to detect the stressful conditions and to optimize the human tasks. The paper proposes a mixed reality (MR) set-up where operators are digitalized and monitored to analyse both physical and cognitive ergonomics. It is useful to predict design criticalities and improve the global system design. An industrial case study has been developed in collaboration with CNH Industrial to demonstrate how the proposed set-up is used for design for serviceability, on the basis of experimental evidence

Acute effects of surgery on emotion and personality of brain tumor patients: Surgery impact, histological aspects, and recovery

Background. Cognitive effects of brain surgery for the removal of intracranial tumors are still under investigation. For many basic sensory/motor or language-based functions, focal, albeit transient, cognitive deficits have been reported low-grade gliomas (LGGs); however, the effects of surgery on higher-level cognitive functions are still largely unknown. It has recently been shown that, following brain tumors, damage to different brain regions causes a variety of deficits at different levels in the perception and interpretation of emotions and intentions. However, the effects of different tumor histologies and, more importantly, the effects of surgery on these functions have not been examined. Methods. The performance of 66 patients affected by high-grade glioma (HGG), LGG, and meningioma on 4 tasks tapping different levels of perception and interpretations of emotion and intentions was assessed before, immediately after, and (for LGG patients) 4 months following surgery. Results. Results showed that HGG patients were generally already impaired in the more perceptual tasks before surgery and did not show surgery effects. Conversely, LGG patients, who were unimpaired before surgery, showed a significant deficit in perceptual tasks immediately after surgery that was recovered within few months. Meningioma patients were substantially unimpaired in all tasks. Conclusions. These results show that surgery can be relatively safe for LGG patients with regard to the higher-level, more complex cognitive functions and can provide further useful information to the neurosurgeon and improve communication with both the patient and the relatives about possible changes that can occur immediately after surgery

The value of immunohistochemical research on PCNA, p53 and heat shock proteins in prostate cancer management: a review.

This review addresses the significance of the expression of proliferating cell nuclear antigen (PCNA), p53 and some heat shock proteins (Hsps) in prostate carcinoma (PC). In fact, PCNA and p53 are two widely discussed tools in PC diagno- sis, mainly because of the controversy regarding the signifi- cance of their expression during prostate cancer development and progression. At the same time, only few studies have shown the potential role of Hsps in carcinogenesis and their overexpression in pre-neoplastic and neoplastic lesions of the prostate. We briefly describe the physiological roles of Hsps in normal cells, and the significance of their immunohistochem- ical detection in PC as well as in pre-cancerous lesions of the prostate. We will also discuss the possible functional interac- tions of these molecules in both dysplastic and neoplastic cell

Extracellular Vesicles-Based Drug Delivery Systems: A New Challenge and the Exemplum of Malignant Pleural Mesothelioma

Research for the most selective drug delivery to tumors represents a fascinating key target in science. Alongside the artificial delivery systems identified in the last decades (e.g., liposomes), a family of natural extracellular vesicles (EVs) has gained increasing focus for their potential use in delivering anticancer compounds. EVs are released by all cell types to mediate cell-to-cell communication both at the paracrine and the systemic levels, suggesting a role for them as an ideal nano-delivery system. Malignant pleural mesothelioma (MPM) stands out among currently untreatable tumors, also due to the difficulties in achieving an early diagnosis. Thus, early diagnosis and treatment of MPM are both unmet clinical needs. This review looks at indirect and direct evidence that EVs may represent both a new tool for allowing an early diagnosis of MPM and a potential new delivery system for more efficient therapeutic strategies. Since MPM is a relatively rare malignant tumor and preclinical MPM models developed to date are very few and not reliable, this review will report data obtained in other tumor types, suggesting the potential use of EVs in mesothelioma patients as well

The choice of μ-vinyliminium ligand substituents is key to optimize the antiproliferative activity of related diiron complexes

Diiron vinyliminium complexes constitute a large family of organometallics displaying a promising anticancer potential. The complexes [Fe2Cp2(CO)(mu-CO){mu-eta(1):eta(3)-C(R-3)C(R-4)CN(R-1)(R-2)}]CF3SO3 (2a-c, 4a-d) were synthesized, assessed for their behavior in aqueous solutions (D2O solubility, Log P-ow, stability in D2O/Me2SO-d(6) mixture at 37 degrees C over 48 h) and investigated for their antiproliferative activity against A2780 and A2780cisR ovarian cancer cell lines and the nontumoral one Balb/3T3 clone A31. Cytotoxicity data collected for 50 vinyliminium complexes were correlated with the structural properties (i.e. the different R-1-R-4 substituents) using the partial least squares methodology. A clear positive correlation emerged between the octanol-water partition coefficient and the relative antiproliferative activity on ovarian cancer cell lines, both of which appear as uncorrelated to the cancer cell selectivity. However, the different effects played by the R-1-R-4 substituents allow tracing guidelines for the development of novel, more effective compounds. Based on these results, three additional complexes (4p-r) were designed, synthesized and biologically investigated, revealing their ability to hamper thioredoxin reductase enzyme and to induce cancer cell production of reactive oxygen species