Solar Sail Structural Analysis via Improved Finite Element Modeling

Despite the existence of many studies about the structural analysis of a square solar sail, the need of obtaining reliable numerical results still poses a number of practical issues to be solved. The aim of this paper is to propose a new method that improves the existing analysis techniques. In this sense, the solar sail is modelled using distributed sail-boom connections, and its structural behavior in free flight is studied, using the inertia relief method, at different incidence angles of the incoming solar radiation. The proposed approach is able to circumvent the onset of numerical convergence problems by means of suitable strategies. A non-linear analysis is carried out starting from an initial geometrical configuration in which the whole solar sail is perturbed using a linear combination of the first global buckling modes, obtained with a static eigenvalue analysis. Key points of the procedure are the application of a correct sail pre-stress, a clever choice of the type of elements to be used in the finite element analysis and the use of a suitable mesh refinement. The performance of the new approach have been successfully tested on square solar sails with side length varying from relatively small to medium-large sizes, in the range 10m - 100m. A detailed analysis is presented for a reference 20m x 20m square solar sail, where the paper shows that the suggested procedure is able to guarantee accurate results without the need of additional stabilization technique. In particular, the vibration global mode shapes and frequencies of the solar sail are correctly described even in presence of unsymmetrical loading conditions. In other terms, the numerical analysis is completed without any convergence problem and any disturbing local modes

Successful Preservation of Native BCR::ABL1 in Chronic Myeloid Leukemia Primary Leukocytes Reveals a Reduced Kinase Activity

Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by the acquisition of t(9;22) generating the fusion tyrosine kinase BCR::ABL1. However, despite the crucial role of this protein in the dysregulation of numerous signal transduction pathways, a direct measure of BCR::ABL1 kinase activity in chronic phase (CP) CML was never accomplished due to intense degradative activity present in mature leukocytes. Therefore, we developed a procedure suitable to preserve BCR::ABL1 protein under non-denaturing, neutral pH conditions in primary, chronic phase (CP)-CML samples. As a result, specific kinase activity was detected utilizing a biotinylated peptide substrate highly selective for c-ABL1. Furthermore, through this approach, BCR::ABL1 kinase activity was barely detectable in CP-CML compared to Ph+ acute lymphoblastic leukemia primary samples, where kinase activity is comparable to those measured in Ph+ cell lines. These in vitro findings provide the first direct measure of BCR::ABL1 kinase activity in primary CP-CML and reveal the presence of a still uncharacterized inhibitory mechanism that maintains BCR::ABL1 in a low activity state in CP-CML despite its overexpression

Regulative Loop between \u3b2-catenin and Protein Tyrosine Receptor Type \u3b3 in Chronic Myeloid Leukemia

Protein tyrosine phosphatase receptor type \u3b3 (PTPRG) is a tumor suppressor gene, down-regulated in Chronic Myeloid Leukemia (CML) cells by the hypermethylation of its promoter region. \u3b2-catenin (CTNNB1) is a critical regulator of Leukemic Stem Cells (LSC) maintenance and CML proliferation. This study aims to demonstrate the antagonistic regulation between \u3b2-catenin and PTPRG in CML cells. The specific inhibition of PTPRG increases the activation state of BCR-ABL1 and modulates the expression of the BCR-ABL1- downstream gene \u3b2-Catenin. PTPRG was found to be capable of dephosphorylating \u3b2-catenin, eventually causing its cytosolic destabilization and degradation in cells expressing PTPRG. Furthermore, we demonstrated that the increased expression of \u3b2-catenin in PTPRG-negative CML cell lines correlates with DNA (cytosine-5)-methyl transferase 1 (DNMT1) over-expression, which is responsible for PTPRG promoter hypermethylation, while its inhibition or down-regulation correlates with PTPRG re-expression. We finally confirmed the role of PTPRG in regulating BCR-ABL1 and \u3b2-catenin phosphorylation in primary human CML samples. We describe here, for the first time, the existence of a regulative loop occurring between PTPRG and \u3b2-catenin, whose reciprocal imbalance affects the proliferation kinetics of CML cells

Enfoque híbrido en la educación permanente de profesionales de enfermería sobre dejar de fumar

Objetivo: Desenvolver e validar o conteúdo de uma intervenção educativa sobre cessação do tabagismo aos profissionais de enfermagem utilizando abordagem híbrida. Método: Estudo de desenvolvimento e validação por consenso de especialistas do curso "Cessação do Tabagismo" para profissionais de enfermagem sobre abordagens ao paciente tabagista conduzido no ano de 2018. Para refinamento e validação do conteúdo final contou-se com amostra de conveniência composta por 12 profissionais com expertise na temática e considerado 80% de consenso entre os participantes. Resultados: A construção do curso envolveu a escolha dos assuntos, produção e validação dos conteúdos. Como estratégia de ensino utilizou-se abordagem híbrida que possui etapa on-line interativa e um encontro presencial para discussão de conceitos e troca de experiências. Conclusão: O curso utilizando método híbrido de ensino se mostrou inovador, de baixo custo e com grande capacidade de difusão do conhecimento, sendo um importante aliado à educação permanente em saúde.Objective: To develop and validate the content of an educational intervention on smoking cessation for Nursing professionals using a Blended Learning approach. Method: A development and validation study by consensus of experts of the "Smoking Cessation" course for Nursing professionals on approaches to the smoking patient carried out in 2018. For refinement and validation of the final content, a convenience sample was made up of 12 professionals with expertise in the subject natter and an 80% consensus among the participants was considered. Results: The construction of the course involved the choice of subjects, production, and content validation. As a teaching strategy, Blended Learning was used, which has an interactive online stage and a face-to-face meeting to discuss concepts and exchange experiences. Conclusion: The course using a Blended Learning method proved to be innovative, low-cost, and with great capacity for disseminating knowledge, being an important ally to permanent education in health.Objetivo: Desarrollar y validar el contenido de una intervención educativa sobre el abandono del hábito de fumar para profesionales de enfermería utilizando un enfoque híbrido. Método: Estudio de desarrollo y validación por consenso de especialistas del curso "Dejar de fumar" para profesionales de enfermería sobre abordajes a pacientes fumadores realizado en 2018. Para refinar y validar el contenido final, se conformó una muestra de conveniencia de 12 profesionales con experiencia en el tema y se consideró consenso del 80% entre los participantes. Resultados: La elaboración del curso implicó la elección de temas, producción y validación de contenido. Como estrategia de enseñanza, se utilizó un enfoque híbrido, que tiene una etapa interactiva online y un encuentro presencial para debatir conceptos e intercambiar experiencias. Conclusión: El curso que utiliza el método de enseñanza híbrido demostró ser innovador, de bajo costo y con gran capacidad para difundir conocimiento, siendo un importante aliado para la educación permanente en salud

No serological evidence for neuronal damage or reactive gliosis in neuro-COVID-19 patients with long-term persistent headache

Recent studies have indicated that long-term neurological sequelae after COVID-19 are not accompanied by an increase of canonical biomarkers of central nervous system injury in blood, but subgroup stratifications are lacking. This is a particular concern in chronic headache, which can be a leading symptom of Post-COVID diseases associated with neuronal damage such as vasculitis or autoimmune encephalitis. We here compared patients with mild Post-COVID-19 syndrome and persistent headache (persistent Post-COVID-19 headache) lasting longer than 12 weeks after the initial serological diagnosis, to patients with mild and severe COVID-19 and COVID-19-negative controls. Levels of neurofilament light chain and glial fibrillary astrocytic protein, i.e. markers of neuronal damage and reactive astrogliosis, were lower in blood from patients with persistent Post-COVID-19 headache compared to patients with severe COVID-19. Hence, our pilot serological study indicates that long-term Post-COVID-19 headache may not be a sign of underlying neuronal damage or neuroinflammation

Gene expression landscape of Chronic Myeloid Leukemia K562 cells overexpressing the tumor suppressor gene PTPRG

This study concerns the analysis of the modulation of Chronic Myeloid Leukemia (CML) cell model K562 transcriptome following transfection with the tumor suppressor gene encoding for Protein Tyrosine Phosphatase Receptor Type G (PTPRG) and treatment with the tyrosine kinase inhibitor (TKI) Imatinib. Specifically, we aimed at identifying genes whose level of expression is altered by PTPRG modulation and Imatinib concentration. Statistical tests as differential expression analysis (DEA) supported by gene set enrichment analysis (GSEA) and modern methods of ontological term analysis are presented along with some results of current interest for forthcoming experimental research in the field of the transcriptomic landscape of CML. In particular, we present two methods that differ in the order of the analysis steps. After a gene selection based on fold-change value thresholding, we applied statistical tests to select differentially expressed genes. Therefore, we applied two different methods on the set of differentially expressed genes. With the first method (Method 1), we implemented GSEA, followed by the identification of transcription factors. With the second method (Method 2), we first selected the transcription factors from the set of differentially expressed genes and implemented GSEA on this set. Method 1 is a standard method commonly used in this type of analysis, while Method 2 is unconventional and is motivated by the intention to identify transcription factors more specifically involved in biological processes relevant to the CML condition. Both methods have been equipped in ontological knowledge mining and word cloud analysis, as elements of novelty in our analytical procedure. Data analysis identified RARG and CD36 as a potential PTPRG up-regulated genes, suggesting a possible induction of cell differentiation toward an erithromyeloid phenotype. The prediction was confirmed at the mRNA and protein level, further validating the approach and identifying a new molecular mechanism of tumor suppression governed by PTPRG in a CML context

Effect of Tocilizumab vs Standard Care on Clinical Worsening in Patients Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial

The coronavirus disease 2019 (COVID-19) pandemic is threatening billions of people worldwide. Tocilizumab has shown promising results in retrospective studies in patients with COVID-19 pneumonia with a good safety profile

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age