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Fingerprint of volcanic forcing on the ENSO-Indian monsoon coupling
Coupling of the El Niño-Southern Oscillation (ENSO) and Indian monsoon (IM) is central to seasonal summer monsoon rainfall predictions over the Indian subcontinent, although a nonstationary relationship between the two nonlinear phenomena can limit seasonal predictability. Radiative effects of volcanic aerosols injected into the stratosphere during large volcanic eruptions (LVEs) tend to alter ENSO evolution; however, their impact on ENSO-IM coupling remains unclear. Here, we investigate how LVEs influence the nonlinear behavior of the ENSO and IM dynamical systems using historical data, 25 paleoclimate reconstructions, last-millennium climate simulations, large-ensemble targeted climate sensitivity experiments, and advanced analysis techniques. Our findings show that LVEs promote a significantly enhanced phase-synchronization of the ENSO and IM oscillations, due to an increase in the angular frequency of ENSO. The results also shed innovative insights into the physical mechanism underlying the LVE-induced enhancement of ENSO-IM coupling and strengthen the prospects for improved seasonal monsoon predictions
T-Cell Assays for Tuberculosis Infection: Deriving Cut-Offs for Conversions Using Reproducibility Data
Although interferon-gamma release assays (IGRA) are promising alternatives to the tuberculin skin test, interpretation of repeated testing results is hampered by lack of evidence on optimal cut-offs for conversions and reversions. A logical start is to determine the within-person variability of T-cell responses during serial testing.We performed a pilot study in India, to evaluate the short-term reproducibility of QuantiFERON-TB Gold In Tube assay (QFT) among 14 healthcare workers (HCWs) who underwent 4 serial QFT tests on day 0, 3, 9 and 12. QFT ELISA was repeated twice on the same sets of specimens. We assessed two types of reproducibility: 1) test-retest reproducibility (between-test variability), and 2) within-person reproducibility over time. Test-retest reproducibility: with dichotomous test results, extremely high concordance was noticed between two tests performed on the same sets of specimens: of the 56 samples, the test and re-test results agreed for all but 2 individuals (kappa = 0.94). Discordance was noted in subjects who had IFN-gamma values around the cut-off point, with both increases and decreases noted. With continuous IFN-gamma results, re-test results tended to produce higher estimates of IFN-gamma than the original test. Within-person reproducibility: when continuous IFN-gamma data were analyzed, the within-person reproducibility was moderate to high. While persons with negative QFT results generally stayed negative, positive results tended to vary over time. Our data showed that increases of more than 16% in the IFN-gamma levels are statistically improbable in the short-term.Conservatively assuming that long-term variability might be at least twice higher than short-term, we hypothesize that a QFT conversion requires two conditions to be met: 1) change from negative to positive result, and 2) at least 30% increase in the baseline IFN-gamma response. Larger studies are needed to confirm our preliminary findings, and determine the conversion thresholds for IGRAs
Development of a Fast SARS-CoV-2 IgG ELISA, Based on Receptor-Binding Domain, and Its Comparative Evaluation Using Temporally Segregated Samples From RT-PCR Positive Individuals
SARS-CoV-2 antibody detection assays are crucial for gathering seroepidemiological information and monitoring the sustainability of antibody response against the virus. The SARS-CoV-2 Spike protein's receptor-binding domain (RBD) is a very specific target for anti-SARS-CoV-2 antibodies detection. Moreover, many neutralizing antibodies are mapped to this domain, linking antibody response to RBD with neutralizing potential. Detection of IgG antibodies, rather than IgM or total antibodies, against RBD is likely to play a larger role in understanding antibody-mediated protection and vaccine response. Here we describe a rapid and stable RBD-based IgG ELISA test obtained through extensive optimization of the assay components and conditions. The test showed a specificity of 99.79% (95% CI: 98.82-99.99%) in a panel of pre-pandemic samples (n = 470) from different groups, i.e., pregnancy, fever, HCV, HBV, and autoantibodies positive. Test sensitivity was evaluated using sera from SARS-CoV-2 RT-PCR positive individuals (n = 312) and found to be 53.33% (95% CI: 37.87-68.34%), 80.47% (95% CI: 72.53-86.94%), and 88.24% (95% CI: 82.05-92.88%) in panel 1 (days 0-13), panel 2 (days 14-20) and panel 3 (days 21-27), respectively. Higher sensitivity was achieved in symptomatic individuals and reached 92.14% (95% CI: 86.38-96.01%) for panel 3. Our test, with a shorter runtime, showed higher sensitivity than parallelly tested commercial ELISAs for SARS-CoV-2-IgG, i.e., Euroimmun and Zydus, even when equivocal results in the commercial ELISAs were considered positive. None of the tests, which are using different antigens, could detect anti-SARS-CoV-2 IgGs in 10.5% RT-PCR positive individuals by the fourth week, suggesting the lack of IgG response
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