Language universals rely on social cognition: Computational models of the use of this and that to redirect the receiver’s attention

Demonstratives—simple referential devices like this and that—are linguistic universals, but their meaning varies cross-linguistically. In languages like English and Italian, demonstratives are thought to encode the referent’s distance from the producer (e.g., that one means “the one far away from me”), while in others, like Portuguese and Spanish, they encode relative distance from both producer and receiver (e.g., aquel means “the one far away from both of us”). Here we propose that demonstratives are also sensitive to the receiver’s focus of attention, hence requiring a deeper form of social cognition than previously thought. We provide initial empirical and computational evidence for this idea, suggesting that producers use demonstratives to redirect the receiver’s attention towards the intended referent, rather than only to indicate its physical distance

Sleep/wake cycle alterations as a cause of neurodegenerative diseases : A Mendelian randomization study

Sleep and/or wake cycle alterations are common in neurodegenerative diseases (ND). Our aim was to determine whether there is a causal relationship between sleep and/or wake cycle patterns and ND (Parkinson's disease (PD) age at onset (AAO), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS)) using two-sample Mendelian Randomization (MR). We selected 12 sleep traits with available Genome-Wide Association Study (GWAS) to evaluate their causal relationship with the ND risk through Inverse-Variance Weighted regression as main analysis. We used as outcome the latest ND GWAS with available summary-statistics: PD-AAO (N = 17,996), AD (N = 21,235) and ALS (N = 40,136). MR results pointed to a causal effect of subjective and objective-measured morning chronotype on later PD-AAO (95%CI:0.33-1.81, p = 8.47×10 and 95%CI:-7.28 to -4.44, p = 5.87×10, respectively). Sleep efficiency was causally associated with a decreased AD risk (95%CI:-20.408 to -0.66, p = 0.04) and daytime sleepiness with an increased ALS risk (95%CI:0.15 to 1.61, p = 0.01). Our study suggests that sleep and/or wake patterns have causal relationship with ND. Given that sleep and/or wake patterns are modifiable risk factors, sleep interventions should be investigated as a potential treatment in PD-AAO, AD and ALS

Very Accurate Time-Frequency Representation of Induction Motors Harmonics for Fault Diagnosis Under Load Variations

Induction motors work under steady-state in many applications. Nevertheless, in some cases they experience periodic load fluctuations, which generate constant frequency harmonics close to variable frequency bar breakage harmonics. In these cases, time-frequency (t-f) transforms are better suited than steady-state analysis since the fault harmonic frequencies change in time. Even if the healthy and faulty frequencies do not overlap in the spectrum, if the speed is unknown, it is difficult to distinguish the constant frequency healthy harmonic from the variable frequency bar breakage harmonic. On the other hand, transient techniques present in technical literature are not precise enough to deal with both the changing frequency of the bar breakage harmonic and a close constant frequency (as the one generated by most of the periodic load fluctuations). To achieve reliable results under these challenging situations, a very precise time-frequency transform must be used, enabling to simultaneously draw the constant and variable frequencies, even if they are very close in the t-f plane. The Dragon-Transform is here proposed to address the problem. It is shown through simulation and experimental results, how it enables to very accurately plot up to five faulty harmonics evolutions, distinguishing at the same time the constant frequency of the load oscillation, traced as a very thin horizontal line. Precision is so high that even the oscillations caused by ripple effect can be observed for the first time in technical literature, enhancing the reliability of the diagnosis performed, and opening the path for a true solution of the problem

Agricultura urbana agroecológica na perspectiva da promoção da saúde

A agricultura urbana tem sido tema de diversas pesquisas no contexto brasileiro e no mundo, principalmente no que diz respeito à geração de trabalho e renda. O presente artigo tem por objetivo sistematizar a experiência do projeto Colhendo Sustentabilidade: práticas comunitárias de segurança alimentar e agricultura urbana (PCS), realizado em Embu das Artes, região metropolitana de São Paulo, durante o período compreendido entre 2008 e 2011, analisando-o sob a ótica da Promoção da Saúde (PS). Foram sujeitos da pesquisa os participantes, os técnicos dos serviços públicos envolvidos e integrantes da equipe técnica do projeto. Os dados foram obtidos através da realização de três oficinas de sistematização, seguidas de outra em que os resultados foram apresentados aos participantes, e também por meio de entrevistas com informantes-chave. Os mesmos foram analisados à luz dos princípios e campos de ação da PS. As conclusões revelaram a agricultura urbana agroecológica (AUA) como ferramenta promotora de saúde por contribuir com o fortalecimento do protagonismo individual e comunitário, empoderamento, criação de ambientes favoráveis à saúde, bem como seu potencial para a multiplicação de "saberes", pelos envolvidos, sobre temas relacionados à geração de renda, saúde e meio ambiente

Columnar cell lesions and subsequent breast cancer risk: a nested case-control study

Introduction: Histologic and genetic evidence suggests that at least some columnar cell lesions (CCL) of the breast represent precursor lesions in the low-grade breast neoplasia pathway. However, the risk of subsequent breast cancer associated with the presence of CCL in a benign breast biopsy is poorly understood.Methods The authors examined the association between the presence of CCL and subsequent breast cancer risk in a nested case-control study of benign breast disease (BBD) and breast cancer within the Nurses' Health Studies (394 cases, 1,606 controls). Benign breast biopsy slides were reviewed by pathologists and CCL presence assessed. Logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs) for the association between CCL and breast cancer risk. Results: Women with CCL (140 cases, 448 controls) had an increased risk of breast cancer compared with those without CCL (OR = 1.44, 95% CI: 1.14 to 1.83), although this was attenuated and became non-significant after adjustment for the histologic category of BBD (OR = 1.20, 95% CI: 0.94 to 1.54). CCL presence was associated with the greatest risk of breast cancer for those with nonproliferative BBD (OR = 1.36, 95% CI: 0.79 to 2.37) and the lowest risk for those with atypical hyperplasia (AH) (OR = 1.10, 95% CI: 0.65 to 1.87); however, this apparent heterogeneity in risk across BBD categories was not significant (P for interaction between CCL presence and BBD category = 0.77). Conclusions: These results provide evidence that CCL may be an important marker of breast cancer risk in women with BBD but suggest that CCL do not increase breast cancer risk independently of concurrent proliferative changes in the breast

Guía de práctica clínica para el tratamiento del cáncer de próstata metastásico hormonosensible en el Seguro Social del Perú (EsSalud)

Introduction: This article summarizes the clinical practice guideline (CPG) for the treatment of metastatic hormone-sensitive prostate cancer in the Social Security of Peru (EsSalud). Objective: To provide evidence-based clinical recommendations for the treatment of adults with hormone-sensitive metastatic adenocarcinoma of the prostate with de novo or recurrent presentation and high or low metastatic volume in EsSalud. Methods: A guideline development group (GDG) was formed, which included specialist physicians and methodologists, who formulated clinical questions. Systematic searches were conducted for systematic reviews and - when deemed relevant - primary studies in PubMed during 2022. Evidence was selected to answer each of the clinical questions posed. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. In periodic working meetings, the GEG used the GRADE methodology to review the evidence and formulate recommendations. The CPG was reviewed by external experts before its approval. Results: The CPG addressed 6 clinical questions, divided into 2 main topics: considerations on androgen deprivation therapy (ADT) and ADT combined with other therapies. Based on these questions, 10 recommendations were formulated (4 strong and 6 conditional), and 6 points of good clinical practice. Conclusion: Evidence-based recommendations were issued for the management of patients with this pathology.Introducción: Este artículo resume la guía de práctica clínica (GPC) para el tratamiento del cáncer de próstata metastásico hormonosensible en el Seguro Social del Perú (EsSalud). Objetivo: Proveer recomendaciones clínicas basadas en evidencia para el tratamiento de adultos con adenocarcinoma de próstata metastásico hormonosensible con presentación de novo o recurrente y de alto o bajo volumen metastásico en EsSalud. Métodos: Se conformó un grupo elaborador de la guía (GEG) que incluyó médicos especialistas y metodólogos, el cual formuló preguntas clínicas. Se realizaron búsquedas sistemáticas de revisiones sistemáticas y –cuando fue considerado pertinente– estudios primarios en PubMed durante el 2022. Se seleccionó la evidencia para responder cada una de las preguntas clínicas planteadas. Se evaluó la certeza de evidencia usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). En reuniones de trabajo periódicas, el GEG usó la metodología GRADE para revisar la evidencia y formular las recomendaciones. La GPC fue revisada por expertos externos antes de su aprobación. Resultados: La GPC abordó 6 preguntas clínicas, divididas en 2 temas principales: consideraciones sobre la terapia de deprivación androgénica (TDA) y TDA combinada con otras terapias. En base a dichas preguntas se formularon 10 recomendaciones (4 fuertes y 6 condicionales) y 6 puntos de buena práctica clínica. Conclusión: Se emitieron recomendaciones basadas en evidencia para el manejo de pacientes con esta patología

Epigenetic Activation of SOX11 in Lymphoid Neoplasms by Histone Modifications

Recent studies have shown aberrant expression of SOX11 in various types of aggressive B-cell neoplasms. To elucidate the molecular mechanisms leading to such deregulation, we performed a comprehensive SOX11 gene expression and epigenetic study in stem cells, normal hematopoietic cells and different lymphoid neoplasms. We observed that SOX11 expression is associated with unmethylated DNA and presence of activating histone marks (H3K9/14Ac and H3K4me3) in embryonic stem cells and some aggressive B-cell neoplasms. In contrast, adult stem cells, normal hematopoietic cells and other lymphoid neoplasms do not express SOX11. Such repression was associated with silencing histone marks H3K9me2 and H3K27me3. The SOX11 promoter of non-malignant cells was consistently unmethylated whereas lymphoid neoplasms with silenced SOX11 tended to acquire DNA hypermethylation. SOX11 silencing in cell lines was reversed by the histone deacetylase inhibitor SAHA but not by the DNA methyltransferase inhibitor AZA. These data indicate that, although DNA hypermethylation of SOX11 is frequent in lymphoid neoplasms, it seems to be functionally inert, as SOX11 is already silenced in the hematopoietic system. In contrast, the pathogenic role of SOX11 is associated with its de novo expression in some aggressive lymphoid malignancies, which is mediated by a shift from inactivating to activating histone modifications

Management of hepatitis C virus genotype 4: recommendations of an international expert panel.

HCV has been classified into no fewer than six major genotypes and a series of subtypes. Each HCV genotype is unique with respect to its nucleotide sequence, geographic distribution, and response to therapy. Genotypes 1, 2, and 3 are common throughout North America and Europe. HCV genotype 4 (HCV-4) is common in the Middle East and in Africa, where it is responsible for more than 80% of HCV infections. It has recently spread to several European countries. HCV-4 is considered a major cause of chronic hepatitis, cirrhosis, hepatocellular carcinoma, and liver transplantation in these regions. Although HCV-4 is the cause of approximately 20% of the 170 million cases of chronic hepatitis C in the world, it has not been the subject of widespread research. Therefore, this document, drafted by a panel of international experts, aimed to review current knowledge on the epidemiology, natural history, clinical, histological features, and treatment of HCV-4 infections

Rate and duration of hospitalisation for acute pulmonary embolism in the real-world clinical practice of different countries : Analysis from the RIETE registry

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