Application of Al-Cu-W-Ta graded density impactors in dynamic ramp compression experiments

Graded density impactors (GDIs) are used to dynamically compress materials to extreme conditions. Two modifications to a previously developed Mg-Cu-W GDI are made in this work before using it in a dynamic compression experiment: Mg is replaced with Al and a Ta disk is glued to the back. The Mg phase is replaced by Al because FCC Al remains solid to higher pressure along its Hugoniot compared to Mg. The addition of the Ta disk creates a constant particle velocity regime and facilitates a definition of peak pressure states. Microstructure analysis, profilometry, and ultrasonic C-scans of the Al-Cu-W GDI all confirm excellent uniformity. We evaluated signal variation in the radial direction of a dynamically compressed Al-LiF bilayer target to evaluate the contribution of spatial nonuniformity to errors. Velocity traces from five photon Doppler velocimetry (PDV) probes located at different radial distances from the center of the target varied at most by 1.1% with a root mean square of 0.3% during the compression ramp, demonstrating low PDV measurement error over a relatively large experimental area. The experimental PDV data also agrees well with 1D simulations that use inputs from predictive characterization models developed for the material properties resulting from tape casting, laminating, and powder consolidation processes. Low measurement error during quasi-isentropic compression, leading to better precision, ensures a robust platform to reach extreme compression and low-temperature recovery states and facilitates discovery via synthesis, quenching, and preservation of new high-pressure phases

Application of Al-Cu-W-Ta graded density impactors in dynamic ramp compression experiments

Graded density impactors (GDIs) are used to dynamically compress materials to extreme conditions. Two modifications to a previously developed Mg-Cu-W GDI are made in this work before using it in a dynamic compression experiment: Mg is replaced with Al and a Ta disk is glued to the back. The Mg phase is replaced by Al because FCC Al remains solid to higher pressure along its Hugoniot compared to Mg. The addition of the Ta disk creates a constant particle velocity regime and facilitates a definition of peak pressure states. Microstructure analysis, profilometry, and ultrasonic C-scans of the Al-Cu-W GDI all confirm excellent uniformity. We evaluated signal variation in the radial direction of a dynamically compressed Al-LiF bilayer target to evaluate the contribution of spatial nonuniformity to errors. Velocity traces from five photon Doppler velocimetry (PDV) probes located at different radial distances from the center of the target varied at most by 1.1% with a root mean square of 0.3% during the compression ramp, demonstrating low PDV measurement error over a relatively large experimental area. The experimental PDV data also agrees well with 1D simulations that use inputs from predictive characterization models developed for the material properties resulting from tape casting, laminating, and powder consolidation processes. Low measurement error during quasi-isentropic compression, leading to better precision, ensures a robust platform to reach extreme compression and low-temperature recovery states and facilitates discovery via synthesis, quenching, and preservation of new high-pressure phases

e-Pilly TROP Maladies infectieuses tropicales

L’e-Pilly TROP est un ouvrage d’infectiologie tropicale destiné aux médecins et aux étudiants en médecine des pays francophones du Sud. La prise en compte des différents niveaux de la pyramide sanitaire dans ces pays le rend aussi accessible aux infirmiers des centres de santé communautaires urbains et des structures de santé intermédiaires des zones rurales. Par définition, les Pays En Développement accroissant progressivement leurs capacités de diagnostic biologique et de traitement, les outils de prise en charge correspondent aux moyens des niveaux périphériques comme à ceux des niveaux hospitaliers de référence

Cumulative Burden of Colorectal Cancer-Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer.

BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC. METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants. RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 × 10-5). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings. CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures

Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations

Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values < 0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice

Physiological normoxia and absence of EGF is required for the long-term propagation of anterior neural precursors from human pluripotent cells

Widespread use of human pluripotent stem cells (hPSCs) to study neuronal physiology and function is hindered by the ongoing need for specialist expertise in converting hPSCs to neural precursor cells (NPCs). Here, we describe a new methodology to generate cryo-preservable hPSC-derived NPCs that retain an anterior identity and are propagatable long-term prior to terminal differentiation, thus abrogating regular de novo neuralization. Key to achieving passagable NPCs without loss of identity is the combination of both absence of EGF and propagation in physiological levels (3%) of O2. NPCs generated in this way display a stable long-term anterior forebrain identity and importantly retain developmental competence to patterning signals. Moreover, compared to NPCs maintained at ambient O2 (21%), they exhibit enhanced uniformity and speed of functional maturation, yielding both deep and upper layer cortical excitatory neurons. These neurons display multiple attributes including the capability to form functional synapses and undergo activity-dependent gene regulation. The platform described achieves long-term maintenance of anterior neural precursors that can give rise to forebrain neurones in abundance, enabling standardised functional studies of neural stem cell maintenance, lineage choice and neuronal functional maturation for neurodevelopmental research and disease-modelling