Safety and Pharmacokinetics of Intranasally Administered Heparin

Purpose: Intranasally administered unfractionated heparin (UFH) and other sulfated polysaccharides are potential prophylactics for COVID-19. The purpose of this research was to measure the safety and pharmacokinetics of clearance of intranasally administered UFH solution from the nasal cavity. Methods: Double-blinded daily intranasal dosing in C57Bl6 mice with four doses (60 ng to 60 μg) of UFH was carried out for fourteen consecutive days, with both blood coagulation measurements and subject adverse event monitoring. The pharmacokinetics of fluorescent-labeled UFH clearance from the nasal cavity were measured in mice by in vivo imaging. Intranasal UFH at 2000 U/day solution with nasal spray device was tested for safety in a small number of healthy human subjects. Results: UFH showed no evidence of toxicity in mice at any dose measured. No significant changes were observed in activated partial thromboplastin time (aPTT), platelet count, or frequency of minor irritant events over vehicle-only control. Human subjects showed no significant changes in aPTT time, international normalized ratio (INR), or platelet count over baseline measurements. No serious adverse events were observed. In vivo imaging in a mouse model showed a single phase clearance of UFH from the nasal cavity. After 12 h, 3.2% of the administered UFH remained in the nasal cavity, decaying to background levels by 48 h. Conclusions: UFH showed no toxic effects for extended daily intranasal dosing in mice as well as humans. The clearance kinetics of intranasal heparin solution from the nasal cavity indicates potentially protective levels for up to 12 h after dosing

Origin of negative cerium anomalies in subduction-related volcanic samples: Constraints from Ce and Nd isotopes

Negative Cerium (Ce) anomalies are observed in chondrite-normalized Rare Earth Element patterns from various volcanic arc suites. These anomalies are well defined in volcanic rocks from the Mariana arc and have been interpreted as the result of addition of subducted sediments to the arc magma sources. This study combines ¹⁴³Nd/¹⁴⁴Nd and ¹³⁸Ce/¹⁴²Ce isotope measurements in Mariana volcanic rocks that have Ce anomalies ranging from 0.97 to 0.90. The dataset includes sediments sampled immediately before subduction at the Mariana Trench (Sites 801 and 802 of ODP Leg 129) and primitive basalts from the Southern Mariana Trough (back-arc basin). Binary mixing models between the local depleted mantle and an enriched end-member using both types of sediment (biosiliceous and volcaniclastic) found in the sedimentary column in front of the arc are calculated. Marianas arc lavas have Ce and Nd isotopic compositions that require <2.5% of a sediment component derived from the volcaniclastics. With this proportion of sediment, most of the Ce/Ce* range measured in lavas is reproduced. Thus, this study confirms that the origin of the Ce anomalies in the Mariana arc magmas can be principally attributed to recycling of trench sediments through active subduction. The participation of a component derived from biosiliceous sediments does not explain the Ce-Nd isotope composition of the lavas because the involved proportion is too high (up to 8%) in comparison to results obtained from other geochemical proxys. Using this end-member, the modeled Ce anomalies are also too high (0.91–0.84) in comparison to those measured in lavas. Various processes and conditions are able to generate Ce anomalies: oxygen fugacity, residual mineral phases, partial melting, fractional crystallization and tropical weathering. Their influence in the case of Mariana volcanic arc magmas seems to be very limited but partial melting effect may explain the lowest measured Ce/Ce* values. Magmatic processes cannot be definitely ruled out in producing Ce anomalies in other arc system environments. Additional experimental data, however, are needed for a better understanding of the behavior of cerium relative to its neighboring elements. Also, this study highlights the importance of using local depleted mantle and sediments to model the isotopic compositions of arc lavas

The History, Relevance, and Applications of the Periodic System in Geochemistry

Geochemistry is a discipline in the earth sciences concerned with understanding the chemistry of the Earth and what that chemistry tells us about the processes that control the formation and evolution of Earth materials and the planet itself. The periodic table and the periodic system, as developed by Mendeleev and others in the nineteenth century, are as important in geochemistry as in other areas of chemistry. In fact, systemisation of the myriad of observations that geochemists make is perhaps even more important in this branch of chemistry, given the huge variability in the nature of Earth materials – from the Fe-rich core, through the silicate-dominated mantle and crust, to the volatile-rich ocean and atmosphere. This systemisation started in the eighteenth century, when geochemistry did not yet exist as a separate pursuit in itself. Mineralogy, one of the disciplines that eventually became geochemistry, was central to the discovery of the elements, and nineteenth-century mineralogists played a key role in this endeavour. Early “geochemists” continued this systemisation effort into the twentieth century, particularly highlighted in the career of V.M. Goldschmidt. The focus of the modern discipline of geochemistry has moved well beyond classification, in order to invert the information held in the properties of elements across the periodic table and their distribution across Earth and planetary materials, to learn about the physicochemical processes that shaped the Earth and other planets, on all scales. We illustrate this approach with key examples, those rooted in the patterns inherent in the periodic law as well as those that exploit concepts that only became familiar after Mendeleev, such as stable and radiogenic isotopes

President Truman's Approach to the National Emergency Strike Problem

Political Scienc

Zirconium Isotope and Its application to Early Silicate Differentiation of Earth and Mars

International audienc

Evidence for anorthositic crust formed on an inner solar system planetesimal

Co-signée avec un laboratoire étrangerInternational audiencedoi: 10.7185/geochemlet.1921 During the first million years of solar system history, planetesimals experienced extensive melting powered by the radioactive decay of 26 Al (Lee et al., 1977). To date, the only known anorthositic crust on a solar system body is that of the Moon, formed by plagioclase flotation on top of the magma ocean (Wood et al., 1970). Here we show evidence from the ungrouped achondrite meteorite Northwest Africa (NWA) 8486 that an anorthositic crust formed on a planetes-imal very early in solar system history (<1.7 Ma). NWA 8486 displays the highest anomalies in Eu and Sr found in achondrites so far and, for the first time, this characteristic is also identified in clinopyroxene. Elemental modelling , together with calculated timescales for crystal settling, show that only the melting of an anorthosite can produce NWA 8486 within the first 5 million years of solar system history. Our results indicate that such a differentiation scenario was achievable over short timescales within the inner solar system, and must have contributed to the making and elemental budget of the terrestrial planets