The temporal dynamics of deictic communication

Deixis – a fundamental part of communication – involves combinations of speech, gesture and eye-gaze, yet little is known about the temporal dynamics of this coordination. The authors analysed eye-gaze, pointing gestures and verbal productions in 514 deictic episodes during triadic, semi-naturalistic, book-reading sessions performed by Italian children (1;08–2;07) and their caregivers. Results show three new findings. First, deictic communication is overwhelmingly preceded and accompanied by shared attention (of consistent duration) on an object, and only sometimes by disjoint attention. Second, children are synchronously multimodal (conveying information via speech, pointing gesture and eye-gaze) in their deictic communications. Third, the form of deictic communication used is not related to the complexity of the linguistic structures of the sample. Deictic communication is remarkably consistent in children ranging from approximately 1;08 to 2;07 years of age

Analogical levelling in the Majorcan Catalan demonstrative system

Demonstratives are cross-linguistically widespread expressions. The use of demonstratives is flexible due to their semantic elasticity, which allows them to describe more or less extensive regions or referents in a communicative scenario. The constant remapping between demonstratives and referents might lead to a restructuring of the deictic system itself in accordance with the parameters affecting its use. To that end, we analyzed the structural changes affecting demonstratives in Majorcan Catalan by analysing whether speakers use three or two terms (aquest/aqueix/aquell vs. aquest/aquell) to convey spatial information. We also assessed whether any change in the adnominal/pronominal forms mirrored locative adverbs reduction. We elicited the production of demonstratives in 36 simultaneous Majorcan/Spanish bilinguals via a psycholinguistic experiment and we found two main results. First, simultaneous bilingual speakers do not extensively use the term aqueix to convey information related to physical distance. Second, the pronominal/adnominal reduction from three- to two-terms differs from the adverbial reduction. In the first case, aqueix is dropping out of the system, while locative adverbs present a shift with substitution of açí for aquí. Overall, our results shed new light on how the Majorcan Catalan demonstrative system is structured and explain structural changes in terms of ‘analogical levelling’ in paradigmatic relations

Clinical, histopathological and molecular characterization of hypoplastic myelodysplastic syndrome

n/

Spatial communication systems across languages reflect universal action constraints

The extent to which languages share properties reflecting the non-linguistic constraints of the speakers who speak them is key to the debate regarding the relationship between language and cognition. A critical case is spatial communication, where it has been argued that semantic universals should exist, if anywhere. Here, using an experimental paradigm able to separate variation within a language from variation between languages, we tested the use of spatial demonstratives—the most fundamental and frequent spatial terms across languages. In n = 874 speakers across 29 languages, we show that speakers of all tested languages use spatial demonstratives as a function of being able to reach or act on an object being referred to. In some languages, the position of the addressee is also relevant in selecting between demonstrative forms. Commonalities and differences across languages in spatial communication can be understood in terms of universal constraints on action shaping spatial language and cognition

Il Late Talker: indagine neurolinguistica sulla "comunicazione" del ritardo.

Il presente lavoro vuole creare il profilo del soggetto Late Talker espressivi, soggetti che a 24 mesi hanno un vocabolario produttivo inferiore alle 50 parole e non presentano la fase combinatoria. L'assenza di danni neuroevolutivi, uditivi ed affettivi accompagna, in maniera imprescindibile, tale ritardo. Sulla base di un modello teorico Usage-based, ho prima evidenziato i rischi putativi e gli indici predittivi del ritardo, per poi passare ad un'analisi statistica (Anova) delle interazioni tra rischi ed indici in un gruppo di 32 soggetti LT. I risultati evidenziano una forte incidenza della familiarità e dell'età precoce dell'inizio dell'eventuale trattamento, sottolineando l'importanza di un'identificazione precoce. Due dei soggetti LT sono stati sottoposti ad un ulteriore confronto con un gruppo di controllo,con età cronologica tra i 20 ed i 36 mesi, per la valutazione comparata della produzione verbale e non verbale. Tanto la produzione verbale quanto quella non verbale mostrano uno slittamento temporale in avanti del soggetto LT rispetto al gruppo di controllo. Il gesto, al pari della produzione verbale si presenta quale ottimo indice predittivo, mentre la sincronia dello sguardo risulta essere significativamente predittiva solo quanto il ritardo linguistico è recettivo e non solo espressivo. The present work aims at creating an expressive late talking profile. Late talking children present a delay in the amount of expressive vocabulary (less than 50 words) and no combinatory phase at the age of 24 months, in absence of neurodevelopmental problems, auditory deficits and affective deprivations. I used a Usage-based model to focus on putative risks and indexes of prediction for the delay. 32 subjects with expressive language delay participated to the interactive analysis between indexes and risks (Anova). Results highlight on a significant predictive effect for familiarity and age of treatment beginning, supporting the importance of an early identification. 2 subjects with expressive language delay were also compared to a control group (age 20-36) for a second analysis aiming at confronting verbal and nonverbal performances. Results on verbal and nonverbal performances describe the delay as a temporal shift. Gesture, as well as verbal production, is identified as a significant predictive index. Gaze synchrony is not predictive in expressive language delay, but in compromised comprehension

Specific Expression of a New Bruton Tyrosine Kinase Isoform (p65BTK) in the Glioblastoma Gemistocytic Histotype

Bruton’s tyrosine-kinase (BTK) is a non-receptor tyrosine kinase recently associated with glioma tumorigenesis and a novel prognostic marker for poor survival in patients with glioma. The p65BTK is a novel BTK isoform involved in different pathways of drug resistance of solid tumors, thus we aimed to investigate the expression and the putative role of p65BTK in tumors of the central nervous system (CNS). We selected a large cohort of patients with glial tumors (n = 71) and analyzed the expression of p65BTK in different histotypes and correlation with clinical parameters. Sections were stained with glial fibrillary acidic protein (GFAP), p53, epidermal growth factor receptor (EGFR), S100, vimentin, and epithelial membrane antigen (EMA) antibodies. Glioma stem cell (GSC) lines, isolated from glioblastoma multiforme (GBM), were treated with different concentrations of ibrutinib, a specific inhibitor of BTK, in order to evaluate their metabolic activity, mitotic index and mortality. Moreover, an orthotopic xenotransplant of GSC from human GBM was used to evaluate the expression of p65BTK in the brain of immunodeficient mice. p65BTK was expressed in GSC and in gemistocytes in human gliomas at different histological grade. We found a significant correlation between BTK expression and low-grade (LG) tumors (p ≤ 0.05) and overall survival (OS) of patients with grade III gliomas (p ≤ 0.05), suggestive of worst prognosis. Interestingly, the expression of p65BTK remained restricted exclusively to gemistocytic cells in the xenograft mouse model. Ibrutinib administration significantly reduced metabolic activity and mitotic index and increased mortality in GSC, highlighting the specific role of p65BTK in cell proliferation and survival. In conclusion, our data demonstrated that p65BTK is expressed in glioma tumors, restricted to gemistocytic cells, has a key role in GSC and has a bad prognostic value, thus highlighting the importance of future research for targeted therapy of human gliomas

Relationship between clone metrics and clinical outcome in clonal cytopenia

Clonal cytopenia of undetermined significance (CCUS) is associated with an increased risk of developing a myeloid neoplasm with myelodysplasia (MN). To identify the features of the mutant clone(s) that is associatedwith clinical phenotype and progression, we studied the following cohorts of individuals: 311 patients with idiopathic cytopenia of undetermined significance (ICUS), 532 community-dwelling individuals without hematologic phenotype (n 5 355) or with unexplained anemia (n 5 177), and 592 patients with overt MN. Ninety-two of 311 (30%) patients with ICUS carried a somatic genetic lesion that signaled CCUS. Clonal hematopoiesis (CH) was detected in 19.7% and 27.7% of nonanemic and anemic community-dwelling individuals, respectively. Different mutation patterns and variant allele frequencies (VAFs) (clone metrics parameters) were observed in the conditions studied. Recurrent mutation patterns exhibited different VAFs associated with marrow dysplasia (0.17-0.48), indicating variable clinical expressivity of mutant clones. Unsupervised clustering analysis based on mutation profiles identified 2 major clusters, characterized by isolated DNMT3A mutations (CH-like cluster) or combinatorial mutation patterns (MN-like cluster), and showing different overall survival (HR, 1.8). In patients with CCUS, the 2 clusters had different risk of progression toMN(HR, 2.7). Within the MN-like cluster, distinct subsets with different risk of progression to MN were identified based on clone metrics. These findings unveil marked variability in the clinical expressivity of myeloid driver genes and underline the limitations of morphologic dysplasia for clinical staging of mutant hematopoietic clones. Clone metrics appears to be critical for informing clinical decision-making in patients with clonal cytopenia

Clinical significance of somatic mutation in unexplained blood cytopenia

Unexplained blood cytopenias, in particular anemia, are often found in older persons. The relationship between these cytopenias and myeloid neoplasms like myelodysplastic syndromes is currently poorly defined. We studied a prospective cohort of patients with unexplained cytopenia with the aim to estimate the predictive value of somatic mutations for identifying subjects with, or at risk of developing a myeloid neoplasm. The study included a learning cohort of 683 consecutive patients investigated for unexplained cytopenia, and a validation cohort of 190 patients referred for suspected myeloid neoplasm. Using granulocyte DNA, we looked for somatic mutations in 40 genes that are recurrently mutated in myeloid malignancies. Overall, 435/683 patients carried a somatic mutation in at least one of these genes. Carrying one somatic mutation with a variant allele frequency equal to or greater than 0.10, or carrying two or more mutations had a positive predictive value for diagnosis of myeloid neoplasm equal to 0.86 and 0.88, respectively. Spliceosome gene mutations and co-mutation patterns involving TET2, DNMT3A, or ASXL1 had positive predictive values for myeloid neoplasm ranging from 0.86 to 1.0. Within subjects with inconclusive diagnostic findings, carrying one or more somatic mutations was associated with a high probability of developing a myeloid neoplasm during follow-up (HR=13.9, P<.001). The predictive values of mutation analysis were confirmed in the independent validation cohort. The findings of this study indicate that mutation analysis on peripheral blood granulocytes may significantly improve the current diagnostic approach to unexplained cytopenia, and more generally the diagnostic accuracy of myeloid neoplasms

phase ii study of sequential infusion of donor lymphocyte infusion and cytokine induced killer cells for patients relapsed after allogeneic hematopoietic stem cell transplantation

Abstract Seventy-four patients who relapsed after allogeneic stem cell transplantation were enrolled in a phase IIA study and treated with the sequential infusion of donor lymphocyte infusion (DLI) followed by cytokine-induced killer (CIK) cells. Seventy-three patients were available for the intention to treat analysis. At least 1 infusion of CIK cells was given to 59 patients, whereas 43 patients received the complete cell therapy planned (58%). Overall, 12 patients (16%) developed acute graft-versus-host disease (aGVHD) of grades I to II in 7 cases and grades III to IV in 5). In 8 of 12 cases, aGVHD developed during DLI treatment, leading to interruption of the cellular program in 3 patients, whereas in the remaining 5 cases aGVHD was controlled by steroids treatment, thus allowing the subsequent planned administration of CIK cells. Chronic GVHD (cGVHD) was observed in 11 patients (15%). A complete response was observed in 19 (26%), partial response in 3 (4%), stable disease in 8 (11%), early death in 2 (3%), and disease progression in 41 (56%). At 1 and 3 years, rates of progression-free survival were 31% and 29%, whereas rates of overall survival were 51% and 40%, respectively. By multivariate analysis, the type of relapse, the presence of cGVHD, and a short