How to Improve Demining Activities Through Gender-sensitive Mine Risk Education

Until recently, mine action was widely perceived as a military and technical field where an almost exclusively male staff planned and implemented activities. However, there is still a need for a better understanding of what mine-affected communities can gain from including gender and age perspectives in mine action and how the different pillars of mine action mutually improve the quality and impact of mine action programs

Talleres de Baby Sign como SAAC y su influencia en el desarrollo del lenguaje de infantes de 12 a 21 meses

Este estudio tuvo como objetivo general evidenciar la influencia de los talleres de Baby Sign en el desarrollo del lenguaje en infantes de 12 a 21 meses, el tipo y diseño de investigación fue aplicada pre experimental con enfoque cuantitativo. Con población de 20 madres de familia y 20 infantes, como instrumento de recolección de datos se usó el checklist para medir la etapa lingüística y el desarrollo del lenguaje avanzado comparando los resultados obtenidos en el pre y post test. Para la prueba de hipótesis, se usaron las pruebas de Kolmogórov-Smirnov y Shapiro- Wilk que determinaron una significancia <.001, rechazándose la hipótesis nula y se aceptó la hipótesis alterna. Por lo tanto, existió una diferencia significativa entre los resultados del pre y post test, concluyéndose que los talleres de Baby Sign benefician significativamente el desarrollo del lenguaje en infantes de 12 a 21 meses, en especial durante la etapa lingüística y el desarrollo del lenguaje avanzado

Phase transition kinetics revealed in laser-heated dynamic diamond anvil cells

We report on a novel approach to dynamic compression of materials that bridges the gap between previous static- and dynamic- compression techniques, allowing to explore a wide range of pathways in the pressure-temperature space. By combining a dynamic-diamond anvil cell setup with double-sided laser-heating and in situ X-ray diffraction, we are able to perform dynamic compression at high temperature and characterize structural transitions with unprecedented time resolution. Using this method, we investigate the $\gamma-\epsilon$ phase transition of iron under dynamic compression for the first time, reaching compression rates of hundreds of GPa/s and temperatures of 2000 K. Our results demonstrate a distinct response of the $\gamma-\epsilon$ and $\alpha-\epsilon$ transitions to the high compression rates achieved. These findings open up new avenues to study tailored dynamic compression pathways in the pressure-temperature space and highlight the potential of this platform to capture kinetic effects in a diamond anvil cell.Comment: Reworked the text and figures to be more in line with the format of PR

Phase transition kinetics revealed by <i>in situ</i> x-ray diffraction in laser-heated dynamic diamond anvil cells

We report successful coupling of dynamic loading in a diamond anvil cell and stable laser heating, which enables compression rates up to 500 GPa/s along high-temperature isotherms. Dynamic loading in a diamond-anvil cell allows exploration of a wider range of pathways in the pressure-temperature space compared to conventional dynamic compression techniques. By in situ x-ray diffraction, we are able to characterize and monitor the structural transitions with the appropriate time resolution i.e., millisecond timescales. Using this method, we investigate the γ−ε phase transition of iron under dynamic compression, reaching compression rates of hundreds of GPa/s and temperatures of 2000 K. Our results demonstrate a distinct response of the γ−ε and α− ε transitions to the high compression rates achieved, possibly due to the different transition mechanisms. These findings open up new avenues to study tailored dynamic compression pathways in the pressure-temperature space and highlight the potential of this platform to capture kinetic effects (over ms time scales) in a diamond anvil cell

Induction of death receptor 5 expression in tumor vasculature by perifosine restores the vascular disruption activity of TRAIL-expressing CD34(+) cells.

The proapoptotic death receptor 5 (DR5) expressed by tumor associated endothelial cells (TECs) mediates vascular disrupting effects of human CD34(+) cells engineered to express membrane-bound tumor necrosis factor-related apoptosis-inducing ligand (CD34-TRAIL (+) cells) in mice. Indeed, lack of DR5 on TECs causes resistance to CD34-TRAIL (+) cells. By xenografting in nonobese diabetic/severe combined immunodeficient mice the TRAIL-resistant lymphoma cell line SU-DHL-4V, which generates tumors lacking endothelial DR5 expression, here we demonstrate for the first time that the Akt inhibitor perifosine induces in vivo DR5 expression on TECs, thereby overcoming tumor resistance to the vascular disruption activity of CD34-TRAIL (+) cells. In fact, CD34-TRAIL (+) cells combined with perifosine, but not CD34-TRAIL (+) cells alone, exerted marked antivascular effects and caused a threefold increase of hemorrhagic necrosis in SU-DHL-4V tumors. Consistent with lack of DR5 expression, CD34-TRAIL (+) cells failed to affect the growth of SU-DHL-4V tumors, but CD34-TRAIL (+) cells plus perifosine reduced tumor volumes by 60 % compared with controls. In view of future clinical studies using membrane-bound TRAIL, our results highlight a strategy to rescue patients with primary or acquired resistance due to the lack of DR5 expression in tumor vasculature

Strategies of Increased Protein Intake in ELBW Infants Fed by Human Milk Lead to Long Term Benefits

Objective: The aim of this observational study was to evaluate the effects of two different protein intake regimes on feeding tolerance, in-hospital growth, anthropometric data and psychomotor outcome up to 24 months corrected age (CA) in extremely low birth-weight (ELBW; birth weight &lt;1000 g) infants.Methods: During the period 2008–2013, 52 ELBW infants admitted at birth to two Neonatal Intensive Care Units of Emilia Romagna (Italy) were fed according to different protocols of protein fortification of human milk: an estimated protein intakes at maximum fortification levels of 3.5 gr/kg/day in the Standard Nutrition Population-SNP group (n = 26) and 4.8 g/kg/day in the Aggressive Nutrition Population-ANP group (n = 26). During hospitalization, infants' growth, biochemical indices of nutritional status, enteral intake, feeding tolerance, clinical history and morbidity were evaluated. After discharge, anthropometric data and psychomotor outcome, evaluated by Revised Griffiths Mental Development Scales (GMDS-R) 0–2 years, were assessed up to 24 months CA.Results: During hospitalization, the ANP group showed significantly higher weight (18.87 vs. 15.20 g/kg/day) and head circumference (0.70 vs. 0.52 cm/week) growth rates compared to SNP, less days of parenteral nutrition (7.36 ± 2.7 vs. 37.75 ± 29.6) and of hospitalization (60.0 ± 13.3 vs. 78.08 ± 21.32). After discharge, ANP infants had a greater head circumference compared to SNP (45.64 ± 0.29; 46.80 ± 0.31). Furthermore, the General Quotient of GMDS-R mean scores in the SNP group significantly decreased from 12 to 24 months CA, while no difference was seen in the ANP group.Conclusions: Increased protein intake may provide short and long term benefits in terms of growth and neurodevelopment in human milk-fed ELBW infants

NOTCH1-mutated chronic lymphocytic leukemia displays high endoplasmic reticulum stress response with druggable potential

IntroductionConstitutive activation of NOTCH1-wild-type (NT1-WT) signaling is associated with poor outcomes in chronic lymphocytic leukemia (CLL), and NOTCH1 mutation (c.7541_7542delCT), which potentiates NOTCH1 signaling, worsens the prognosis. However, the specific mechanisms of NOTCH1 deregulation are still poorly understood. Accumulative evidence mentioned endoplasmic reticulum (ER) stress/unfolded protein response (UPR) as a key targetable pathway in CLL. In this study, we investigated the impact of NOTCH1 deregulation on CLL cell response to ER stress induction, with the aim of identifying new therapeutic opportunities for CLL.MethodsWe performed a bioinformatics analysis of NOTCH1-mutated (NT1-M) and NT1-WT CLL to identify differentially expressed genes (DEGs) using the rank product test. Quantitative real-time polymerase chain reaction (qPCR), Western blotting, cytosolic Ca2+, and annexin V/propidium iodide (PI) assay were used to detect curcumin ER stress induction effects. A median-effect equation was used for drug combination tests. The experimental mouse model Eμ-TCL1 was used to evaluate the impact of ER stress exacerbation by curcumin treatment on the progression of leukemic cells and NOTCH1 signaling.Results and discussionBioinformatics analysis revealed gene enrichment of the components of the ER stress/UPR pathway in NT1-M compared to those in NT1-WT CLL. Ectopic expression of NOTCH1 mutation upregulated the levels of ER stress response markers in the PGA1 CLL cell line. Primary NT1-M CLL was more sensitive to curcumin as documented by a significant perturbation in Ca2+ homeostasis and higher expression of ER stress/UPR markers compared to NT1-WT cells. It was also accompanied by a significantly higher apoptotic response mediated by C/EBP homologous protein (CHOP) expression, caspase 4 cleavage, and downregulation of NOTCH1 signaling in NT1-M CLL cells. Curcumin potentiated the apoptotic effect of venetoclax in NT1-M CLL cells. In Eμ-TCL1 leukemic mice, the administration of curcumin activated ER stress in splenic B cells ex vivo and significantly reduced the percentage of CD19+/CD5+ cells infiltrating the spleen, liver, and bone marrow (BM). These cellular effects were associated with reduced NOTCH1 activity in leukemic cells and resulted in prolonged survival of curcumin-treated mice. Overall, our results indicate that ER stress induction in NT1-M CLL might represent a new therapeutic opportunity for these high-risk CLL patients and improve the therapeutic effect of drugs currently used in CLL