A Study of the Residual 39Ar Content in Argon from Underground Sources

The discovery of argon from underground sources with significantly less 39Ar than atmospheric argon was an important step in the development of direct-detection dark matter experiments using argon as the active target. We report on the design and operation of a low background detector with a single phase liquid argon target that was built to study the 39Ar content of the underground argon. Underground argon from the Kinder Morgan CO2 plant in Cortez, Colorado was determined to have less than 0.65% of the 39Ar activity in atmospheric argon.Comment: 21 pages, 10 figure

A Digital One Health framework to integrate data for public health decision-making

The current implementation of One Health (OH) primarily focuses on multi-sectoral collaboration but often overlooks opportunities to integrate contextual and pathogen-related data into a unified data resource. This lack of integration hampers effective, data-driven decision-making in OH activities. In this perspective, we examine the existing strategies for data sharing and identify gaps and barriers to integration. To overcome these challenges, we propose the Digital OH (DOH) framework for data integration, which consolidates data-sharing principles within five pillars for the OH community of practice: (a) Harmonization of standards to establish trust, (b) Automation of data capture to enhance quality and efficiency, (c) Integration of data at point of capture to limit bureaucracy, (d) Onboard data analysis to articulate utility, and (e) Archiving and governance to safeguard the OH data resource. We discuss an upcoming pilot program as a use case focusing on antimicrobial resistance surveillance to illustrate the application of this framework. Our ambition is to leverage technology to create data as a shared resource using DOH not only to overcome current structural barriers but also to address prevailing ethical and legal concerns. By doing so, we can enhance the efficiency and effectiveness of decision-making processes in the OH community of practice, at a national, regional, and international level

A high-throughput chemically induced inflammation assay in zebrafish

Artículo de publicación ISIBackground: Studies on innate immunity have benefited from the introduction of zebrafish as a model system. Transgenic fish expressing fluorescent proteins in leukocyte populations allow direct, quantitative visualization of an inflammatory response in vivo. It has been proposed that this animal model can be used for high-throughput screens aimed at the identification of novel immunomodulatory lead compounds. However, current assays require invasive manipulation of fish individually, thus preventing high-content screening. Results: Here we show that specific, noninvasive damage to lateral line neuromast cells can induce a robust acute inflammatory response. Exposure of fish larvae to sublethal concentrations of copper sulfate selectively damages the sensory hair cell population inducing infiltration of leukocytes to neuromasts within 20 minutes. Inflammation can be assayed in real time using transgenic fish expressing fluorescent proteins in leukocytes or by histochemical assays in fixed larvae. We demonstrate the usefulness of this method for chemical and genetic screens to detect the effect of immunomodulatory compounds and mutations affecting the leukocyte response. Moreover, we transformed the assay into a high-throughput screening method by using a customized automated imaging and processing system that quantifies the magnitude of the inflammatory reaction. Conclusions: This approach allows rapid screening of thousands of compounds or mutagenized zebrafish for effects on inflammation and enables the identification of novel players in the regulation of innate immunity and potential lead compounds toward new immunomodulatory therapies. We have called this method the chemically induced inflammation assay, or ChIn assay.This work was supported by grants to MA from Fondecyt (1070867), FONDAP (15090007), ICM (P06-039F), CORFO-Innova (09MCSS-6705), DFG-Conicyt 075-2009; to CD from UNAB (DI- 01-09/1) and Fondecyt (24090004); to UL from Dopaminet (EU FP7 223744); and to CG by a Marie Curie International Reintegration Grant (EU FP7; PIRG07-GA-2010-267552)

Exposure to Leptospira spp. and associated risk factors in the human, cattle and dog populations in Bhutan

Leptospirosis is a neglected worldwide zoonotic bacterial disease with a high prevalence in subtropical and tropical countries. The prevalence of Leptospira spp. in humans, cattle and dogs is unknown in Bhutan. Therefore, we sought to find out whether humans, cattle or dogs had been infected in the past with leptospires by measuring antibodies in the serum. We therefore collected blood from 864 humans >/=13 years of age, 130 bovines and 84 dogs from different rural and urban areas in Bhutan and tested the serum for antibodies specific for leptospires with a screening of enzyme-linked immunosorbent assays (ELISA) and a confirmatory microscopic agglutination test (MAT). In humans, 17.6% were seropositive by ELISA and 1.6% by MAT. The seropositivity was stronger in bovines (36.9%) and dogs (47.6%). "Having had a fever recently" (OR 5.2, p = 0.004), "working for the military" (OR 26.6, p = 0.028) and "being unemployed" (OR 12.9, p = 0.041) (reference category = housemaker) were statistically significantly associated with seropositivity when controlled for the effects of other risk factors. However, due to the small number of positive test results, the findings on risk factors should be interpreted with caution. Based on the serogroups found in the three species, dogs could be a source of infection for humans, or dogs and humans are exposed to the same environmental risk factors Clinical leptospirosis in humans and domestic animals should be investigated by testing blood and urine for the presence of leptospires by molecular methods (qPCR)

Pulse Shape Analysis and Identification of Multipoint Events in a Large-Volume Proportional Counter in an Experimental Search for 2K Capture Kr-78

A pulse shape analysis algorithm and a method for suppressing the noise component of signals from a large copper proportional counter in the experiment aimed at searching for 2K capture of Kr-78 are described. These signals correspond to a compound event with different numbers of charge clusters due to from primary ionization is formed by these signals. A technique for separating single- and multipoint events and determining the charge in individual clusters is presented. Using the Daubechies wavelets in multiresolutional signal analysis, it is possible to increase the sensitivity and the resolution in extraction of multipoint events in the detector by a factor of 3-4.Comment: 10 pages, 8 figures. submitted to Instruments and Experimental Techniques; ISSN 0020/441

Discovery of underground argon with low level of radioactive 39Ar and possible applications to WIMP dark matter detectors

We report on the first measurement of 39Ar in argon from underground natural gas reservoirs. The gas stored in the US National Helium Reserve was found to contain a low level of 39Ar. The ratio of 39Ar to stable argon was found to be <=4x10-17 (84% C.L.), less than 5% the value in atmospheric argon (39Ar/Ar=8x10-16). The total quantity of argon currently stored in the National Helium Reserve is estimated at 1000 tons. 39Ar represents one of the most important backgrounds in argon detectors for WIMP dark matter searches. The findings reported demonstrate the possibility of constructing large multi-ton argon detectors with low radioactivity suitable for WIMP dark matter searches.Comment: 6 pages, 2 figures, 2 table

Simulation of cell-substrate traction force dynamics in response to soluble factors

Finite element (FE) simulations of contractile responses of vascular muscular thin films (vMTFs) and endothelial cells resting on an array of micro-posts under stimulation of soluble factors were conducted in comparison with experimental measurements reported in literature. Two types of constitutive models were employed in the simulations, i.e. smooth muscle cell type and non-smooth muscle cell type. The time histories of the effects of soluble factors were obtained via calibration against experimental measurements of contractile responses of tissues or cells. The numerical results for vMTFs with micropatterned tissues suggest that the radius of curvature of vMTFs under stimulation of soluble factors is sensitive to width of the micropatterned tissue, i.e. the radius of curvature increases as the tissue width decreases. However, as the tissue response is essentially isometric, the time history of the maximum principal stress of the micropatterned tissues is not sensitive to tissue width. Good agreement has been achieved for predictions of the vasoconstrictor endothelin-1 (ET-1) induced contraction stress between the FE numerical simulation and the experiment based approach of Alford, et al. (2011) for the vMTFs with 40, 60, 80 and 100 μm width patterns. This may suggest the contraction stress is weakly sensitive to the tissue width for these patterns. However, for 20 μm width tissue patterning, the numerical simulation result for contraction stress is less than the average value of experimental measurements, which may suggest the thinner and more elongated spindle-like cells within the 20 μm width tissue patterning have higher contractile output. The constitutive model for non-smooth muscle cells was used to simulate the contractile response of the endothelial cells. The substrate was treated as an effective continuum. For agonists such as Lysophosphatidic acid (LPA) and vascular endothelial growth factor (VEGF), the deformation of the cell diminishes from edge to centre and the central part of the cell is essentially under isometric state. Numerical studies demonstrated the scenarios that cell polarity can be triggered via manipulation of the effective stiffness and Possion’s ratio of the substrate

HIV-1 drug resistance in people on dolutegravir-based antiretroviral therapy:a collaborative cohort analysis

BACKGROUND The widespread use of the integrase strand transfer inhibitor (INSTI) dolutegravir in first-line and second-line antiretroviral therapy (ART) might facilitate emerging resistance. The DTG RESIST study combined data from HIV cohorts to examine patterns of drug resistance mutations (DRMs) and identify risk factors for dolutegravir resistance. METHODS We included cohorts with INSTI resistance data from two collaborations (ART Cohort Collaboration, International epidemiology Databases to Evaluate AIDS in Southern Africa), and the UK Collaborative HIV Cohort. Eight cohorts from Canada, France, Germany, Italy, the Netherlands, Switzerland, South Africa, and the UK contributed data on individuals who were viraemic on dolutegravir-based ART and underwent genotypic resistance testing. Individuals with unknown dolutegravir initiation date were excluded. Resistance levels were categorised using the Stanford algorithm. We identified risk factors for resistance using mixed-effects ordinal logistic regression models. FINDINGS We included 599 people with genotypic resistance testing on dolutegravir-based ART between May 22, 2013, and Dec 20, 2021. Most had HIV-1 subtype B (n=351, 59%), a third had been exposed to first-generation INSTIs (n=193, 32%), 70 (12%) were on dolutegravir dual therapy, and 18 (3%) were on dolutegravir monotherapy. INSTI DRMs were detected in 86 (14%) individuals; 20 (3%) had more than one mutation. Most (n=563, 94%) were susceptible to dolutegravir, seven (1%) had potential low, six (1%) low, 17 (3%) intermediate, and six (1%) high-level dolutegravir resistance. The risk of dolutegravir resistance was higher on dolutegravir monotherapy (adjusted odds ratio [aOR] 34·1, 95% CI 9·93-117) and dolutegravir plus lamivudine dual therapy (aOR 9·21, 2·20-38·6) compared with combination ART, and in the presence of potential low or low (aOR 5·23, 1·32-20·7) or intermediate or high-level (aOR 13·4, 4·55-39·7) nucleoside reverse transcriptase inhibitor (NRTI) resistance. INTERPRETATION Among people with viraemia on dolutegravir-based ART, INSTI DRMs and dolutegravir resistance were rare. NRTI resistance substantially increased the risk of dolutegravir resistance, which is of concern, notably in resource-limited settings. Monitoring is important to prevent resistance at the individual and population level and ensure the long-term sustainability of ART. FUNDING US National Institutes of Health, Swiss National Science Foundation

Markers of early changes in cognition across cohorts of adults with Down syndrome at risk of Alzheimer's disease.

Introduction: Down syndrome (DS), a genetic variant of early onset Alzheimer's disease (AD), lacks a suitable outcome measure for prevention trials targeting pre-dementia stages. Methods: We used cognitive test data collected in several longitudinal aging studies internationally from 312 participants with DS without dementia to identify composites that were sensitive to change over time. We then conducted additional analyses to provide support for the utility of the composites. The composites were presented to an expert panel to determine the most optimal cognitive battery based on predetermined criteria. Results: There were common cognitive domains across site composites, which were sensitive to early decline. The final composite consisted of memory, language/executive functioning, selective attention, orientation, and praxis tests. Discussion: We have identified a composite that is sensitive to early decline and thus may have utility as an outcome measure in trials to prevent or delay symptoms of AD in DS