The ontogeny of discourse structure mimics the development of literature

Discourse varies with age, education, psychiatric state and historical epoch, but the ontogenetic and cultural dynamics of discourse structure remain to be quantitatively characterized. To this end we investigated word graphs obtained from verbal reports of 200 subjects ages 2-58, and 676 literary texts spanning ~5,000 years. In healthy subjects, lexical diversity, graph size, and long-range recurrence departed from initial near-random levels through a monotonic asymptotic increase across ages, while short-range recurrence showed a corresponding decrease. These changes were explained by education and suggest a hierarchical development of discourse structure: short-range recurrence and lexical diversity stabilize after elementary school, but graph size and long-range recurrence only stabilize after high school. This gradual maturation was blurred in psychotic subjects, who maintained in adulthood a near-random structure. In literature, monotonic asymptotic changes over time were remarkable: While lexical diversity, long-range recurrence and graph size increased away from near-randomness, short-range recurrence declined, from above to below random levels. Bronze Age texts are structurally similar to childish or psychotic discourses, but subsequent texts converge abruptly to the healthy adult pattern around the onset of the Axial Age (800-200 BC), a period of pivotal cultural change. Thus, individually as well as historically, discourse maturation increases the range of word recurrence away from randomness.Comment: Natalia Bezerra Mota and Sylvia Pinheiro: Equal contribution Sidarta Ribeiro and Mauro Copelli: Corresponding author

The History of Writing Reflects the Effects of Education on Discourse Structure: Implications for Literacy, Orality, Psychosis and the Axial Age

Background: Graph analysis detects psychosis and literacy acquisition. Bronze Age literature has been proposed to contain childish or psychotic features, which would only have matured during the Axial Age (∼800-200 BC), a putative boundary for contemporary mentality. Method: Graph analysis of literary texts spanning ∼4,500 years shows remarkable asymptotic changes over time. Results: While lexical diversity, long-range recurrence and graph length increase away from randomness, short-range recurrence declines towards random levels. Bronze Age texts are structurally similar to oral reports from literate typical children and literate psychotic adults, but distinct from poetry, and from narratives by preliterate preschoolers or Amerindians. Text structure reconstitutes the “arrow-of-time”, converging to educated adult levels at the Axial Age onset. Conclusion: The educational pathways of oral and literate traditions are structurally divergent, with a decreasing range of recurrence in the former, and an increasing range of recurrence in the latter. Education is seemingly the driving force underlying discourse maturation.Fil: Pinheiro, Sylvia. Universidade Federal do Rio Grande do Norte; BrasilFil: Mota, Natália Bezerra. Universidade Federal de Pernambuco; Brasil. Universidade Federal do Rio Grande do Norte; BrasilFil: Sigman, Mariano. Universidad Torcuato Di Tella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fernandez Slezak, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Investigación en Ciencias de la Computación. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Investigación en Ciencias de la Computación; ArgentinaFil: Guerreiro, Antonio. Universidade Estadual de Campinas; BrasilFil: Tófoli, Luís Fernando. Universidade Estadual de Campinas; BrasilFil: Cecchi, Guillermo. No especifíca;Fil: Copelli, Mauro. No especifíca;Fil: Ribeiro, Sidarta. Universidade Federal do Rio Grande do Norte; Brasi

Imagetic and affective measures of memory reverberation diverge at sleep onset in association with theta rhythm

The ‘day residue’ - the presence of waking memories into dreams - is a century-old concept that remains controver- sial in neuroscience. Even at the psychological level, it remains unclear how waking imagery cedes into dreams. Are visual and affective residues enhanced, modified, or erased at sleep onset? Are they linked, or dissociated? What are the neural correlates of these transformations? To address these questions we combined quantitative se- mantics, sleep EEG markers, visual stimulation, and multiple awakenings to investigate visual and affect residues in hypnagogic imagery at sleep onset. Healthy adults were repeatedly stimulated with an affective image, allowed to sleep and awoken seconds to minutes later, during waking (WK), N1 or N2 sleep stages. ‘Image Residue’ was objectively defined as the formal semantic similarity between oral reports describing the last image visualized before closing the eyes (‘ground image’), and oral reports of subsequent visual imagery (‘hypnagogic imagery). Similarly, ‘Affect Residue’ measured the proximity of affective valences between ‘ground image’ and ‘hypnagogic imagery’. We then compared these grounded measures of two distinct aspects of the ‘day residue’, calculated within participants, to randomly generated values calculated across participants. The results show that Image Residue persisted throughout the transition to sleep, increasing during N1 in proportion to the time spent in this stage. In contrast, the Affect Residue was gradually neutralized as sleep progressed, decreasing in proportion to the time spent in N1 and reaching a minimum during N2. EEG power in the theta band (4.5-6.5 Hz) was inversely correlated with the Image Residue during N1. The results show that the visual and affective aspects of the ‘day residue’ in hypnagogic imagery diverge at sleep onset, possibly decoupling visual contents from strong negative emotions, in association with increased theta rhythm.Neuroimag

Effect of Flow Rate on In Vitro Aerodynamic Performance of NEXThaler® in Comparison with Diskus® and Turbohaler® Dry Powder Inhalers

European and United States Pharmacopoeia compendial procedures for assessing the in vitro emitted dose and aerodynamic size distribution of a dry powder inhaler require that 4.0 L of air at a pressure drop of 4 kPa be drawn through the inhaler. However, the product performance should be investigated using conditions more representative of what is achievable by the patient population. This work compares the delivered dose and the drug deposition profile at different flow rates (30, 40, 60, and 90 L/min) of Foster NEXThaler(®) (beclomethasone dipropionate/formoterol fumarate), Seretide(®) Diskus(®) (fluticasone propionate/salmeterol xinafoate), and Symbicort(®) Turbohaler(®) (budesonide/formoterol fumarate)

New Ligandless C−H Activation Procedure for The Decoration of C‐3 Position of 1H‐Indazole Derivatives

Arylation of heteroaromatic rings is one of the most important strategy for the chemical space exploration (e.g. applied in medicinal chemistry). In the last two decades C H activation reactions emerged as powerful and more sustainable synthetic methods for this kind of functionalization if compared to the classical Pd-catalysed cross-coupling reactions (e. g. Suzuki, Stille, Negishi, Hiyama). A further step in the direction of greater sustainability has been done developing ligandless C H activation procedures with higher appeal for industrial applica- tion. Among the various N-based heterocycles exploited in medicinal chemistry, there is no reported ligandless C H activation for 1H-indazole core, although its potential pharma- ceutical applications. In this work we describe a novel synthetic procedure for the direct arylation/heteroarylation of C-3 position of 1H-indazole which was optimized using the Design of Experiment (DoE) (yield up to 72 %) and confirmed a fulfilling robustness among various aryl/heteroaryl and indazole scopes

Multivariate Analysis of Effects of Asthmatic Patient Respiratory Profiles on the in Vitro Performance of a Reservoir Multidose and a Capsule-Based Dry Powder Inhaler

PURPOSE: The aim of this work was to evaluate the effect of two different dry powder inhalers, of the NGI induction port and Alberta throat and of the actual inspiratory profiles of asthmatic patients on in-vitro drug inhalation performances. METHODS: The two devices considered were a reservoir multidose and a capsule-based inhaler. The formulation used to test the inhalers was a combination of formoterol fumarate and beclomethasone dipropionate. A breath simulator was used to mimic inhalatory patterns previously determined in vivo. A multivariate approach was adopted to estimate the significance of the effect of the investigated variables in the explored domain. RESULTS: Breath simulator was a useful tool to mimic in vitro the in vivo inspiratory profiles of asthmatic patients. The type of throat coupled with the impactor did not affect the aerodynamic distribution of the investigated formulation. However, the type of inhaler and inspiratory profiles affected the respirable dose of drugs. CONCLUSIONS: The multivariate statistical approach demonstrated that the multidose inhaler, released efficiently a high fine particle mass independently from the inspiratory profiles adopted. Differently, the single dose capsule inhaler, showed a significant decrease of fine particle mass of both drugs when the device was activated using the minimum inspiratory volume (592 mL)

Automated analysis of free speech predicts psychosis onset in high-risk youths

Background/Objectives: Psychiatry lacks the objective clinical tests routinely used in other specializations. Novel computerized methods to characterize complex behaviors such as speech could be used to identify and predict psychiatric illness in individuals. AIMS: In this proof-of-principle study, our aim was to test automated speech analyses combined with Machine Learning to predict later psychosis onset in youths at clinical high-risk (CHR) for psychosis. Methods: Thirty-four CHR youths (11 females) had baseline interviews and were assessed quarterly for up to 2.5 years; five transitioned to psychosis. Using automated analysis, transcripts of interviews were evaluated for semantic and syntactic features predicting later psychosis onset. Speech features were fed into a convex hull classification algorithm with leave-one-subject-out cross-validation to assess their predictive value for psychosis outcome. The canonical correlation between the speech features and prodromal symptom ratings was computed. Results: Derived speech features included a Latent Semantic Analysis measure of semantic coherence and two syntactic markers of speech complexity: maximum phrase length and use of determiners (e.g., which). These speech features predicted later psychosis development with 100% accuracy, outperforming classification from clinical interviews. Speech features were significantly correlated with prodromal symptoms. Conclusions: Findings support the utility of automated speech analysis to measure subtle, clinically relevant mental state changes in emergent psychosis. Recent developments in computer science, including natural language processing, could provide the foundation for future development of objective clinical tests for psychiatry

Biomarkers in neomark European project for oral cancers

Oral cavity cancers are the seventh tumor by diffusion worldwide with more than 90% being diagnosed as oral squamous cell carcinomas (OSCCs). According to the latestWHO statistics, OSCC accounts for 5% of the cancer deaths worldwide, being the eighth more lethal cancer entity. Early identification of cancer relapses would have the potentiality to improve the disease control and the patient survival. NeoMark is a European co-funded research project (Seventh Framework Program, Information and Communication Technologies: EU-FP7-ICT-2007-2-22483-NeoMark) that has the objective to identify relevant biomarkers of OSCC recurrence. It integrates high-throughput gene expression analysis in tumor cells and IT-assisted imaging with traditional staging and follow-up protocols to improve the recurrence risk stratification and to obtain the earlier identification of locoregional relapses. The architecture of the project is based on the following key points: – Creation of a web application tool: A unified interface that helps the storage and management of all information – NeoMark database: The heterogeneous NeoMark data (demographics and risk factors; clinical, pathological, and immunohistochemical parameters; filtered and cleaned genomic and imaging data) are stored in a single database – the Integrated Health Record Repository (IHRR) – on a central NeoMark server. The server contains the marker definition functional environment (MDFE), a data analysis module. Based on the heterogeneous input data, it estimates the likelihood of a relapse and identifies OSCC risk factors. – Imaging biomarker extraction: Several biomarkers are obtained from medical images such as CT and MRI scans (size, amount of necrosis from tumor and lymph nodes, etc.). To extract those features, a custom software tool – called the NeoMark Image Processing Tool – has specifically been developed. – Genomic data cleaning and filtering: Extraction of genomic data and filtering of genes with low data quality and of those with high number of missing values. The NeoMark system was trained and initially validated in a multicenter pilot study (three European clinical centers involved: Two in Italy and one in Spain) basing on 86 patients affected by OSCC with a minimum follow-up of 12 months. The clinicians recognized the usefulness of the disease bioprofile (or diseasespecific profile) identified by NeoMark to evaluate the risk of disease reoccurrence of a patient at diagnosis, to stratify patients affected by OSCC at baseline according to the risk of recurrence, and to reserve a “tailored therapy” to each case