Objectives/Goals: Cerebral amyloid angiopathy (CAA) characterized by the accumulation of amyloid-beta in the cerebrovasculature, affects blood vessel integrity leading to brain hemorrhages and an accelerated cognitive decline in Alzheimer’s disease patients. In this study, we are conducting a genome-wide association study to identify genetic risk factors for CAA. Methods/Study Population: We genotyped 1253 additional AD cases using and curated existing genome-wide genotype data from 110 AD and 502 non-AD donors from the Mayo Clinic Brain Bank. We performed QC and imputation of all datasets. We conducted GWAS in AD only (N =  1,363), non-AD only, as well as the combined cohort (N = 1,865) by testing imputed variant dosages for association with square root transformed CAA using linear regression, adjusting for relevant covariates. To assess associations in the context of major CAA risk factors, we performed interaction analysis with APOEe4 presence and sex; and pursued stratified analyses. We collected peripheral gene expression measures using RNA isolated from 188 PAXgene tube samples of 95 donors collected across multiple time points. More than 1/3 of these participants have MRI measures collected. Results/Anticipated Results: Variants at the APOE locus were identified as the most significant in our study. In addition, several other variants with suggestive association were found under the main model adjusting for AD neuropathology (Braak and Thal). LINC-PINT splice variant remained associated with lower CAA scores in AD cases without the APOEe4 risk allele. To enhance the robustness of our findings, we are pursuing further expansion of our study cohort. In the periphery, we expect to identify expression changes associated with neuroimaging indicators of CAA and determine if variants and genes discovered via GWAS are implicated in these changes. Discussion/Significance of Impact: We expect this study will provide further insight into the genetic architecture underlying risk for CAA both in the context of significant AD pathology and without. Characterization of genetic variants and functional outcomes in the context of neuropathology may lead to new avenues of research aimed at identifying biomarkers and therapies to treat CAA

Short- and long-term exposure to inorganic solutions can cause significant degradation of the hydraulic properties of bentonite clay used in geosynthetic clay liners (GCLs). In particular, the increase in hydraulic conductivity due to cation exchange when Na-montmorillonite is subjected to leachates rich in Ca and Mg has caused problems in incinerator ash landfill liners located in wet environments, where large quantities of leachates are generated. Experimental results are presented to evaluate the immediate change in hydraulic conductivity of seven types of GCL clays upon permeation with leachate generated from three ash landfills. The composition of the ash, which is a by-product of the incineration of municipal solid waste (MSW), in turn influences the composition of the resulting leachate. Falling head permeability tests were performed on flexible-wall permeameter specimens, with back-pressure saturation. Chemical analysis shows that the three leachate products contain high, medium, and low concentration Ca and Mg cations. The clay component of GCL materials tested in this study consists of regular and polymer-treated bentonite. Polymer treatment is believed to render the clay non-reactive to many organic and inorganic chemicals. The results of this study indicate that: (1) polymer treatment is generally more beneficial if the clay is first saturated with water and not directly with the leachate; (2) high swell potential of the bentonite is more advantageous than polymer treatment, especially when low hydraulic conductivity is required in the short term and if the clay is pre-hydrated. Experiment setup and special specimen preparation procedures are also discussed.

In this article, we take a global perspective to assess the impact of the exogenous COVID pandemic shock on business confidence. Through a quantitative analysis of 31 advanced and 12 emerging economies over the period from January 2018 to December 2020, we provide a novel investigation of a unique worldwide event, in contrast to the most frequent exogenous shocks, which typically have a more limited local or regional scope. We proxy business expectations with the business confidence indicator or BCI. First, we find that the containment measures for the COVID pandemic have negatively affected business confidence, with the compulsory policies having a greater negative effect on BCI than the voluntary ones. Second, we find positive spillover effects on the local BCIs from the containment measures implemented in neighboring countries. This suggests that business people are not against compulsory measures per se, but rather that they are less inclined to assume the costs of these. Third, we find that while the severity of containment measures has been greater in emerging countries, the negative impact on BCI of these containment measures has been larger in advanced economies.

Catholic Social Teaching in Latin America—portrayed in the documents of the Conference of Latin American Episcopal Conferences (Río, Medellín, Puebla, Santo Domingo, and Aparecida)—seeks to provide pastoral orientations to the social problems of the subcontinent, analyzing reality from a concrete theological perspective: the perspective of the poor. This article analyzes how Latin American problems and the way to diagnose them also appear in the pontifical documents of Pope Francis, especially in Evangelii Gaudium and Laudato Si’, applied to the world context. We conclude that the perspective of Latin American theology continues to be valid and relevant for the faithful throughout the world.

This paper provides a new index of money market and bank lending interest rates in Spain for 1900–1935. New archival evidence reveals a structural change in market interest rates vis-à-vis the official rates charged by the Banco de España (BdE). Before 1914, the BdE rate operated as a ceiling to market rates. The outbreak of the First World War caused market rates to soar and the BdE rate started operating as a floor, as bank liquidity started depending on the BdE. This was accompanied by new banking legislation introduced in 1921, which changed the collateral framework through which the BdE lent to banks. The resulting interest rate index illustrates the persistent impact of financial deglobalisation caused by the outbreak of the War.

On March 10, 1910, Pío Coronel informed his readers that he was abandoning his home in the western province of Pinar del Río and saddling up his horse to set out on an important journalistic and political assignment. The black press journalist noted that once he got wind of Cuban president José Miguel Gómez's plans to set off from the presidential palace on a political campaign across the island, he kissed his wife goodbye and took off in pursuit with little more than a pen and a shoulder bag. In the following weeks, Pío galloped hundreds of miles across the Cuban countryside, or, as he called it, the “ill-fated American Colony,” to report on how black communities from Havana to Guantánamo received President Gómez. In other words, Pío showcased Cuba's black public sphere, which despite its effervescent political and civic life was outside the purview of Cuba's mainstream reporters. As this article argues, it was also largely neglected by subsequent generations of historians.

The effect of competition from other metal ions on the complexation of Ni with isosaccharinic acid, gluconic acid and picolinic acid, at high pH, is described. The competing metal ions used were divalent Co, trivalent Eu and tetravalent Th. In the majority of cases, competition from these metal ions followed the predicted pattern, with most anomalies seeming to be caused by sorption of Ni to the many different solid phases formed in presence of the competing ions. The Ni solid phase was shown to change with time during the course of the study. No major unexplained competition effects were found.

The sorption behaviour of I−, Cs+, Ni2+, Eu3+, Th4+ and UO2+ 2on NRVB (Nirex reference vault backfill) a possible vault backfill, at pH 12.8 was studied. Sorption isotherms generated were compared to results obtained in the presence of cellulose degradation products (CDP). Whereas Cs was not affected by the presence of the organic compounds, a notable reduction in the sorption of Th and Eu to cement was observed. The results also indicated limited removal of Ni from solution (with or without an organic ligand) by sorption, the concentration in solution seemingly being determined solely by solubility processes. In the case of uranium, the presence of CDP increased the sorption to cement by almost one order of magnitude. Further studies into the uptake of CDP by cement are being undertaken to identify the mechanism(s) responsible.

Recently, an exceptional find was made by the Nakum Archaeological Project in an offering deposited deep within the architectural core of the Precolumbian Maya site of Nakum located in northeastern Guatemala. The form of the object and comparisons made to ethnographic analogs indicate that it is a clay beehive, most probably one of the oldest in the Maya area and in the whole of Mesoamerica. Whether the object was used for its intended function or is an emulation, or skeuomorph, of perishable counterparts, remains unknown. The importance of this find lies in the fact that beekeeping is an activity that is traced with difficulty in archaeology. The present paper discusses the discovery of this artifact at Nakum, which dates to the end of the Preclassic period (ca. 100 BC–AD 250/300), in a wider temporal and spatial context and provides new data on Precolumbian beekeeping. We use a broad comparative vantage, drawing on archaeological, epigraphic, and ethnohistorical sources to discuss Mesoamerican beekeeping and its role in both the daily and the ritual lives of the Maya.

The generation and stability of inorganic colloids have been studied under hyperalkaline conditions. For the generation of colloids, intact cores of Bromsgrove Sandstone were flushed with simulated cement leachates, and the eluates were ultrafiltered sequentially (12 μm, 1 μm,0.1 μm and 30 kDa) for the separation of any colloids found. No colloid formation was observed during the experiments; however the analysis by ICPMS of the eluates showed significant increases in Si and Al, indicating silicate mineral dissolution, as well as reduction of the concentrationof Ca in the leachates indicating precipitation of secondary Ca-rich phases. Flow experiments with cement leachates spiked with tritiated water showed a noticeable reduction of the porosity of the sandstone as well as changes in the pore distribution. Additional stability experiments werecarried out using model silica and Fe2O3 colloids. The experiments indicated that the stability of the colloids was mainly controlled by the concentration of Ca in solution and that both types were unstable under the chemical conditions in the alkaline disturbed zone.The presence of cement additives such as superplasticisers could enhance the stability of the colloids.

Radial diffusion experiments have been carried out to assess the migration of 36Cl, as chloride, through a cementitious backfill material. Further experiments in the presence of cellulose degradation products were performed to assess the effect of organic ligands on the extentand rate of chloride diffusion. Results show that breakthrough of 36Cl is dependent on chloride concentration: as the carrier concentration increases, both breakthrough time and the quantity retained by the cement matrix decreases. Experiments in the presence of cellulose degradationproducts also show a decrease in time to initial breakthrough. However, uptake at various carrier concentrations in the presence of organic ligands converges at 45% of the initial concentration as equilibrium is reached. The results are consistent with organic ligands blocking sites on thecement that would otherwise be available for chloride binding, though further work is required to confirm that this is the case. Post-experimental digital autoradiographs of the cement cylinders, and elemental mapping showed evidence of increased 36Cl activity associated with blackash-like particles in the matrix, believed to correspond to partially hydrated glassy calcium-silicate-sulfate-rich clinker.

A total of 63 psychrotolerant bacteria exhibiting resistance to various antibiotics, such as ampicillin, streptomycin and/or trimethoprim, were isolated from diverse sites varying in terms of human influence, from obvious presence to probable absence, on Fildes Peninsula (King George Island, South Shetland Islands). The presence of class 1 integrons in some of these antibiotic resistant isolates was further determined. Plasmids from two isolates (HP19 and CN11) were transferred to Escherichia coli DH5α by conjugation. Sequence analysis of the plasmid from the HP19 isolate exhibited high similarity (~99%) to plasmid p34998-210.894kb of Enterobacter hormaechei subsp. steigerwaltii of clinical origin and confirmed the presence of a dfrA14 cassette in a class 1 integron context. 16S rRNA gene sequence analysis of five of these psychrotolerant isolates indicated similarity with environmental bacteria previously identified as Enterobacter species. Together, these results confirm that there may be no pristine niches for antibiotic resistance gene dissemination.

Citral is a monoterpene commonly found as volatile component in many different aromatic plants. Although many studies have identified the presence of citral in phytotoxic essential oils, this work determines for the first time the potential herbicidal effect of citral on weeds. The use of citral against weeds and crops resulted in the potential for the management of barnyardgrass, redroot pigweed, and ribwort. Clear morphological differences were observed between adult thale cress plants exposed to citral in two different application methods: spraying and watering. Citral-sprayed and citral-watered thale cress plants showed completely different effects after treatment, suggesting that foliar or root absorption can determine the effectiveness of this compound. This work demonstrates that citral is effective not only on seedling metabolism but also on adult plants by inhibiting growth and development altering the plant oxidative status.

The results obtained with neuronal grafting in an animal model of heredo-degenerative ataxia (the pcd mutant mouse) have been extremely useful to unmask new aspects of neural plasticity. The grafted embryonic Purkinje cells invade the deficient molecular layer of the host by migrating radially through adult Bergmann fibers. There, they start building their dendritic trees and, by promoting the axonal sprouting of specific adult neuronal population in a timed sequence, they receive appropriate synaptic contacts, starting ten days after grafting. Twenty-one days after grafting, the grafted Purkinje cells have acquired their adult dendritic pattern and synaptic investment. Both the detailed timetable and the nature of the cellular interactions between embryonic and adult neural cells are remarkably similar to those occurring during normal development. These results raise the possibility that embryonic Purkinje cells can induce in adult neural cells a new type of plasticity, that of recreating a permissive microenvironment for the synaptic integration of the grafted neurons, leading to the anatomical restoration of the cortical circuit of the mutant cerebellum.

Sea cucumbers (phylum Echinodermata) are common members of benthic communities in many marine ecosystems. They function as nutrient recyclers and bioturbators of soft bottoms, and are preyed upon by birds, fishes, mollusks, crustaceans and other taxa. In the Central Mexican Pacific, Islas Marietas harbours a complex and diverse community of corals and benthic invertebrates, with a particularly well-represented assemblage of echinoderms. However, little is known about the diversity of holothurians in the area. Between 2012 and 2014 a bimonthly census was conducted at Islas Marietas, and seven species were recorded for the first time at this location: Holothuria (Halodeima) inornata, Holothuria (Mertensiothuria) hilla, Holothuria (Platyperona) difficilis, Neocucumis veleronis, Lissothuria ornata, Afrocucumis ovulum and Pachythyone pseudolugubris. The absence of previous records of these species may be associated with their low densities and cryptic habits. This report acts to fill a critical knowledge gap in the distribution of holothurians in the eastern tropical Pacific and highlights the under-appreciated biodiversity of this Natural Protected Area.