Exploring the measurement of markedness and its relationship with other linguistic variables

Antonym pair members can be differentiated by each word's markedness-that distinction attributable to the presence or absence of features at morphological or semantic levels. Morphologically marked words incorporate their unmarked counterpart with additional morphs (e.g., "unlucky" vs. "lucky"); properties used to determine semantically marked words (e.g., "short" vs. "long") are less clearly defined. Despite extensive theoretical scrutiny, the lexical properties of markedness have received scant empirical study. The current paper employs an antonym sequencing approach to measure markedness: establishing markedness probabilities for individual words and evaluating their relationship with other lexical properties (e.g., length, frequency, valence). Regression analyses reveal that markedness probability is, as predicted, related to affixation and also strongly related to valence. Our results support the suggestion that antonym sequence is reflected in discourse, and further analysis demonstrates that markedness probabilities, derived from the antonym sequencing task, reflect the ordering of antonyms within natural language. In line with the Pollyanna Hypothesis, we argue that markedness is closely related to valence; language users demonstrate a tendency to present words evaluated positively ahead of those evaluated negatively if given the choice. Future research should consider the relationship of markedness and valence, and the influence of contextual information in determining which member of an antonym pair is marked or unmarked within discourse

Study of chronic low back pain treatment using the Back School

The aim of the present study was to quantitatively analyze the response of patients with chronic low back pain to treatment at the Back School at the IMREA-HCFMUSP. The following scales were used to measure the therapeutic response: the Oswestry Low Back Pain Disability Questionnaire, a Visual Analog Scale (VAS), and a corporal diagram of the pain. The sample was composed of 43 patients with chronic low back pain evaluated, treated, and referred to by the Back School program. The results showed significant improvement among those who completed the program in all three scales applied. Since the period of study was only two months, the results do not support any claim that the Back School is also this effective on long-term treatment of chronic low back pain. Further qualitative and quantitative studies must be carried out in order to support the development of specialized multi-professional teams, who will carry out alterations and improvements in therapeutic resources to the management of chronic low back pain.O objetivo do presente trabalho foi analisar a resposta ao tratamento dos pacientes com dor lombar crônica, atendidos pela “Escola de Postura” do IMREA-HCFMUSP. Os questionários utilizados para avaliação da resposta terapêutica foram a escala “Oswestry Low Back Pain Disability Questionnaire”, a Escala Visual Analógica (EVA), e um diagrama corporal de dor. A amostra foi composta por 43 pacientes com lombalgia crônica encaminhados, avaliados e tratados pela Escola de Postura. Observou-se que os indivíduos que concluíram a Escola apresentaram melhora significativa com relação às três escalas de avaliação aplicadas. Cabe ressaltar que o período de estudo de avaliação da Escola de Postura foi de dois meses, sendo que os resultados não possibilitam afirmar que tal método terapêutico também é eficaz em longo prazo. Mais estudos, quantitativos e qualitativos, devem ser realizados de modo a oferecer subsídios à equipe multiprofissional da Escola que permitam operar mudanças e ampliar recursos terapêuticos no tratamento de pacientes com lombalgia crônica

Testing associations between cannabis use and subcortical volumes in two large population-based samples

Background and aims Disentangling the putative impact of cannabis on brain morphology from other comorbid substance use is critical. After controlling for the effects of nicotine, alcohol and multi‐substance use, this study aimed to determine whether frequent cannabis use is associated with significantly smaller subcortical grey matter volumes. Design Exploratory analyses using mixed linear models, one per region of interest (ROI), were performed whereby individual differences in volume (outcome) at seven subcortical ROIs were regressed onto cannabis and comorbid substance use (predictors). Setting Two large population‐based twin samples from the United States and Australia. Participants A total of 622 young Australian adults [66% female; μage = 25.9, standard deviation SD) = 3.6] and 474 middle‐aged US males (μage = 56.1SD = 2.6) of predominately Anglo‐Saxon ancestry with complete substance use and imaging data. Subjects with a history of stroke or traumatic brain injury were excluded. Measurements Magnetic resonance imaging (MRI) and volumetric segmentation methods were used to estimate volume in seven subcortical ROIs: thalamus, caudate nucleus, putamen, pallidum, hippocampus, amygdala and nucleus accumbens. Substance use measurements included maximum nicotine and alcohol use, total life‐time multi‐substance use, maximum cannabis use in the young adults and regular cannabis use in the middle‐aged males. Findings After correcting for multiple testing (P = 0.007), cannabis use was unrelated to any subcortical ROI. However, maximum nicotine use was associated with significantly smaller thalamus volumes in middle‐aged males. Conclusions In exploratory analyses based on young adult and middle‐aged samples, normal variation in cannabis use is unrelated statistically to individual differences in brain morphology as measured by subcortical volume

EGFR is involved in dermatofibrosarcoma protuberans progression to high grade sarcoma

International audienceDermatofibrosarcoma protuberans (DFSP), amounting to 6% of all soft tissue sarcomas, has a slow growth rate, contrasting with a likelihood for local recurrence and a 10-20% evolution to higher-grade sarcoma, or "transformed DFSP" (DFSP-T). At molecular level, the characteristic COL1A1-PDGFB rearrangement, leading to sustained PDGFR signaling, is not linked to the evolutive potential. Here, we studied EGFR, another tyrosine kinase receptor, using laser-microdissection to select the different histologic components of DFSP (DFSP center, DFSP infiltrative periphery, DFSP-T higher-grade sarcoma), in 22 patients followed over 3 to 156 months. EGFR protein and mRNA were expressed in 13/22 patients with DFSP or DFSP-T, and increased with tumor progression, both in microdissected areas of higher-grade sarcomas and in microdissected areas of local extension. No cancer-associated EGFR gene mutation or copy-number variation, nor any KRAS, BRAF, NRAS hotspot mutations were found in any microdissected area. Among epithelial-mesenchymal transition factors tested, SNAIL 1/2 had the same expression pattern as EGFR while ZEB1/2 or TWIST1/2 did not. Using a proteome profiler phospho-kinase array on 3 DFSP and 3 DFSP-T cryopreserved tissue samples, EGFR phosphorylation was detected in each case. Among EGFR downstream pathways, we found positive correlations between phosphorylation levels of EGFR and STAT5a/b (r = 0.87, p 0.70). We thus demonstrated that in DFSP evolution to high grade sarcoma, EGFR and SNAIL were involved, with EGFR activation and signaling through TOR and STAT5a/b downstream effectors, which could lead on to new therapies for advanced DFSP

Tracking sub-clonal TP53 mutated tumor cells in human metastatic renal cell carcinoma

International audienceRenal Cell Carcinomas (RCCs) are heterogeneous tumors with late acquisition of TP53 abnormalities during their evolution. They harbor TP53 abnormalities in their metastases. We aimed to study TP53 gene alterations in tissue samples from primary and metastatic RCCs in 36 patients followed up over a median of 4.2 years, and in xenografted issued from primary RCCs. In 36 primary RCCs systematically xenografted in mice, and in biopsies of metastases performed whenever possible during patient follow-up, we studied p53expressing tumor cells and TP53 gene abnormalities. We identified TP53 gene alterations in primary tumors, metastases and xenografts. Quantification of tumors cells with TP53 gene alterations showed a significant increase in the metastases compared to the primary RCCs, and, strikingly, the xenografts were similar to the metastases and not to the primary RCCs from which they were derived. Using laser-microdissection of p53-expressing tumor cells, we identified TP53mutated tumor cells in the xenografts derived from the primary RCC, and in a lung metastasis later developed in one patient. The mutation enabled us to track back their origin to a minority sub-clone in the primary heterogeneous RCC. Combining in situ and molecular analyses, we demonstrated a clonal expansion in a living patient with metastatic RCC

Increased risk of brain metastases among patients with melanoma and PROM2 expression in metastatic lymph nodes

International audienceno abstract availabl