scholarly journals Partial Unlock for COVID-19-Like Epidemics Can Save 1-3 Million Lives Worldwide

2020 ◽  
Author(s):  
Robert L. Shuler ◽  
Theodore Koukouvitis ◽  
Dyske Suematsu
Keyword(s):  
Seasonal Effects ◽  
Social Distancing ◽  
Public Response ◽  
Replication Factor ◽  
Population Immunity ◽  
Highly Sensitive ◽  
Low Levels ◽  
Robust Strategies

Objectives: We study partial unlock or reopening interaction with seasonal effects in a managed epidemic to quantify overshoot effects on small and large unlock steps and discover robust strategies for reducing overshoot. Methods: We simulate partial unlock of social distancing for epidemics over a range of replication factor, immunity duration and seasonality factor for strategies targeting immunity thresholds using overshoot optimization. Results: Seasonality change must be taken into account as one of the steps in an easing sequence, and a two step unlock, including seasonal effects, minimizes overshoot and deaths. It may cause undershoot, which causes rebounds and assists survival of the pathogen. Conclusions: Partial easing levels, even low levels for economic relief while waiting on a vaccine, have population immunity thresholds based on the reduced replication rates and may experience overshoot as well. We further find a two step strategy remains highly sensitive to variations in case ratio, replication factor, seasonality and timing. We demonstrate a three or more step strategy is more robust, and conclude that the best possible approach minimizes deaths under a range of likely actual conditions which include public response.

Partial unlock for COVID-19-like epidemics can save 1-3 million lives worldwide (Preprint)

2020 ◽  
Author(s):  
Robert Shuler ◽  
Theodore Koukouvitis ◽  
Dyske Suematsu
Keyword(s):  
Herd Immunity ◽  
Seasonal Effects ◽  
Social Distancing ◽  
Public Response ◽  
Replication Factor ◽  
Population Immunity ◽  
Animal Trials ◽  
Highly Sensitive ◽  
Low Levels ◽  
Initial Peak

BACKGROUND A large percentage of deaths in an epidemic or pandemic can be due to overshoot of herd immunity, either from the initial peak or from planned or unplanned exit from lockdown or social distancing conditions. OBJECTIVE We study partial unlock or reopening interaction with seasonal effects in a managed epidemic to quantify overshoot effects on small and large unlock steps and discover robust strategies for reducing overshoot. METHODS We simulate partial unlock of social distancing for epidemics over a range of replication factor, immunity duration and seasonality factor for strategies targeting immunity thresholds using overshoot optimization. RESULTS Seasonality change must be taken into account as one of the steps in an easing sequence, and a two step unlock, including seasonal effects, minimizes overshoot and deaths. It may cause undershoot, which causes rebounds and assists survival of the pathogen CONCLUSIONS Partial easing levels, even low levels for economic relief while waiting on a vaccine, have population immunity thresholds based on the reduced replication rates and may experience overshoot as well. We further find a two step strategy remains highly sensitive to variations in case ratio, replication factor, seasonality and timing. We demonstrate a three or more step strategy is more robust, and conclude that the best possible approach minimizes deaths under a range of likely actual conditions which include public response. CLINICALTRIAL No human or animal trials were involved.

scholarly journals Bioanalytical screening of low levels of dioxins and dioxin-like PCBs in pig meat (pork) for checking compliance with EU maximum and action levels using highly sensitive “third generation” recombinant H4L7.5c2 rat hepatoma cells

2021 ◽  
Vol 33 (1) ◽  
Author(s):  
Johannes Haedrich ◽  
Claudia Stumpf ◽  
Michael S. Denison
Keyword(s):  
European Union ◽  
Hepatoma Cell ◽  
Animal Origin ◽  
The European Union ◽  
Highly Sensitive ◽  
Commission Regulation ◽  
Pig Meat ◽  
Low Levels ◽  
Action Levels ◽  
Rat Hepatoma

Abstract Background Low maximum and action levels set by the European Union for polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) in pig meat (pork) have led to a demand for reliable and cost-effective bioanalytical screening methods implemented upstream of gas chromatography/high-resolution mass spectrometry confirmatory technology, that can detect low levels of contamination in EU-regulated foods with quick turn-around times. Results Based on the Chemically Activated LUciferase gene eXpression (CALUX) bioassay, extraction and clean-up steps were optimized for recovery and reproducibility within working ranges significantly lower than in current bioassays. A highly sensitive “3rd generation” recombinant rat hepatoma cell line (H4L7.5c2) containing 20 dioxin responsive elements was exposed to pork sample extracts, and their PCDD/Fs and DL-PCBs levels were evaluated by measuring luciferase activity. The method was validated according to the provisions of Commission Regulation (EU) 2017/644 of 5 April 2017 with spiking experiments performed selectively for PCDD/Fs and DL-PCBs and individual calibration for PCDD/Fs, DL-PCBs and the calculated sum of PCDD/Fs and DL-PCBs. The resulting performance parameters met all legal specifications as confirmed by re-calibration using authentic samples. Cut-off concentrations for assessing compliance with low maximum levels and action levels set for PCDD/Fs and DL-PCBs within a range of 0.50–1.25 pg WHO-TEQ/g fat were derived, ensuring low rates of false-compliant results (ß-error < 1%) and keeping the rate of false-noncompliant results well under control (α-error < 12%). Conclusions We present a fast and efficient bioanalytical routine method validated according to the European Union’s legal requirements on the basis of authentic samples, allowing the analyst to reliably identify pork samples and any other EU-regulated foods of animal origin suspected to be noncompliant with a high level of performance and turn-around times of 52 h. This was facilitated in particular by a quick and efficient extraction step followed by selective clean-up, use of a highly sensitive “3rd generation” H4L7.5c2 recombinant rat hepatoma cell CALUX bioassay, and optimized assay performance with improved calibrator precision and reduced lack-of-fit errors. New restrictions are proposed for the calibrator bias and the unspecific background contribution to reportable results. The procedure can utilize comparably small sample amounts and allows an annual throughput of 840–1000 samples per lab technician. The described bioanalytical method contributes to the European Commission's objective of generating accurate and reproducible analytical results according to Commission Regulation (EU) 2017/644 across the European Union.

scholarly journals Public Response, Anxiety and Behaviour during the First Wave of COVID-19 Pandemic in Saudi Arabia

2021 ◽  
Vol 18 (9) ◽  
pp. 4628
Author(s):  
Amani Salem Alqahtani ◽  
Meshael Mohammed Alrasheed ◽  
Ada Mohammed Alqunaibet
Keyword(s):  
Cross Sectional ◽  
Protective Measures ◽  
Policy Makers ◽  
Factors Affecting ◽  
Public Response ◽  
Social Events ◽  
Phone Survey ◽  
Younger Age ◽  
Low Levels ◽  
The Government

This study aims to investigate public response attitude, anxiety, practices and trust in the authorities’ mitigation plan during the first wave of COVID-19 pandemic. A national cross sectional phone survey was conducted among Saudi residents aged 16 years and above. A total of 90,421 (45.2%) individuals participated in the study. Of those, the overall rate of COVID-19 correct knowledge was 82% (mean: 9.84); social media was the most reported source of knowledge. Younger age, low levels of education and foreign residents were associated with poor knowledge. Overall, 49.5% scored 5 or more on the GAD-7 test, indicating anxiety symptoms, 19.2% of them scored 10 and above, suggesting moderate to severe anxiety. Majority of participants (>78%) trusted and supported the interventions implemented by the government to control COVID-19. Social distancing practices among participants was as following, 72.5% stayed at home and avoid going out for nonessential business and 49.5% avoided attending social events and family gatherings. Trust in authorities, being anxious, worry and levels of knowledge about the disease, were the most common factors affecting adoption of the recommended practices. Continuous evaluation of public response about COVID-19, and the effectiveness of protective measures is essential to better inform policy-makers and identify ways of encouraging behaviour change among public during pandemic.

scholarly journals Development and Validation of a High Sensitivity Assay for Measuring p217 + tau in Cerebrospinal Fluid

2020 ◽  
Vol 77 (4) ◽  
pp. 1417-1430
Author(s):  
Gallen Triana-Baltzer ◽  
Kristof Van Kolen ◽  
Clara Theunis ◽  
Setareh Moughadam ◽  
Randy Slemmon ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Amyloid Β ◽  
High Sensitivity ◽  
Csf Biomarkers ◽  
Highly Sensitive ◽  
Good Potential ◽  
Low Levels ◽  
Good Differentiation ◽  
Development And Validation ◽  
Better Than

Background: Early and accurate detection and staging is critical to managing Alzheimer’s disease (AD) and supporting clinical trials. Cerebrospinal fluid (CSF) biomarkers for amyloid-β peptides, tau species, and various neurodegenerative and inflammatory analytes are leading the way in this regard, yet there is room for improved sensitivity and specificity. In particular tau is known to be present in many different fragments, conformations, and post-translationally modified forms. While the exact tau species that might best reflect AD pathology is unknown, a growing body of evidence suggests that forms with high levels of phosphorylation in the mid-region may be especially enriched in AD. Objective: Develop an assay for measuring p217tau in CSF. Methods: Here we describe the development and validation of a novel sELISA for measuring CSF tau species containing phosphorylation at threonines 212 & 217, aka p217 + tau, using the PT3 antibody. Results: While the analyte is present at extremely low levels the assay is sufficiently sensitive and specific to quantitate p217 + tau with excellent precision, accuracy, and dilution linearity, allowing good differentiation between diagnostic subgroups. The p217 + tau measurements appear to track AD pathology better than the commonly used p181tau epitope, suggesting superior diagnostic and staging performance. Finally, the assay can also be configured to differentiate antibody-bound versus antibody-free tau, and therefore can be used to measure target engagement by p217 + tau-targeting immunotherapeutics. Conclusion: The assay for measuring p217 + tau described here is highly sensitive, accurate, precise, dilution linear, and shows good potential for identifying and staging AD.

VARIATION IN MINERAL CONTENT OF SASKATCHEWAN FEED GRAINS

1977 ◽  
Vol 57 (4) ◽  
pp. 679-687 ◽  
Author(s):  
B. D. OWEN ◽  
M. J. FARMER ◽  
F. SOSULSKI ◽  
K. K. WU
Keyword(s):  
Soil Type ◽  
Mineral Content ◽  
Clay Soils ◽  
Seasonal Effects ◽  
Soil Types ◽  
Soil Zone ◽  
Coefficients Of Variation ◽  
Oat Cultivars ◽  
Low Levels ◽  
Gray Soil

The concentration of Ca, P, Mg, K, Zn, Cu, Mn, Fe and Se were determined in wheat, barley and oat cultivars grown in four soil zones incorporating two soil types during a 5-yr period. Ca and K in Saskatchewan grains were much lower than published values, while Zn and Fe values were much higher. Se contents in each grain averaged 0.25 ppm and were substantially below values reported in the literature. Se and Cu levels were extremely variable (CV = 31–81%), but coefficients of variation (CV) for other minerals ranged from 9 to 35%. The effects of season, soil zone, soil type and cultivar on composition of Ca, P, Mg and K were significant in most grains. Seasonal effects on Zn, Cu, Mn and Fe were quite marked, but soil type had little effect and there were few significant differences between cultivars. Grain samples from Gray soil locations were characteristically high in Zn and low in Mn. Average Se content in grain from the Brown soil zone (0.39–0.55 ppm) was highest. There was a progressive decrease through the Dark Brown and Black soils to very low levels in samples from the Gray soil zone (0.06–0.07 ppm). In each type of grain, clay soils were associated with higher Se levels than loam soils.

Advantages of highly sensitive NGS based test to detect low levels of mtDNA mutations and large deletions

Mitochondrion ◽  
2015 ◽  
Vol 24 ◽  
pp. S44-S45
Author(s):  
Hui Yu ◽  
Jing Wang ◽  
Eric Schmitt ◽  
Meagan Palculict ◽  
Michelle Miller ◽  
...  
Keyword(s):  
Mtdna Mutations ◽  
Large Deletions ◽  
Highly Sensitive ◽  
Low Levels

Development of highly sensitive polysilicon nanogap with APTES/GOx based lab-on-chip biosensor to determine low levels of salivary glucose

2014 ◽  
Vol 220 ◽  
pp. 101-111 ◽  
Author(s):  
Sharma Rao Balakrishnan ◽  
U. Hashim ◽  
G.R. Letchumanan ◽  
M. Kashif ◽  
A.R. Ruslinda ◽  
...  
Keyword(s):  
Lab On Chip ◽  
Highly Sensitive ◽  
Low Levels ◽  
On Chip

Expression and epitopic conservation of calponin in different smooth muscles and during development

1996 ◽  
Vol 74 (2) ◽  
pp. 187-196 ◽  
Author(s):  
Jian-Ping Jin ◽  
Michael P. Walsh ◽  
Mary E. Resek ◽  
Gail A. McMartin
Keyword(s):  
Smooth Muscle ◽  
Thin Filament ◽  
Smooth Muscles ◽  
Constitutive Expression ◽  
Young Chick ◽  
Adult Chicken ◽  
Muscle Tissues ◽  
Highly Sensitive ◽  
Cnbr Cleavage ◽  
Low Levels

Calponin is a thin filament associated protein found in smooth muscle as a potential modulator of contraction. Five mouse monoclonal antibodies (mAbs CP1, CP3, CP4, CP7, and CP8) were prepared against chicken gizzard α-calponin. The CP1 epitopic structure is conserved in smooth muscles across vertebrate phyla and is highly sensitive to CNBr cleavage in contrast with the chicken-specific CP4 and the avian–mammalian-specific CP8 epitopes that are resistant to CNBr fragmentation. Using this panel of mAbs against multiple epitopes, only α-calponin was detected in adult chicken smooth muscles and throughout development of the gizzard. Western blotting showed that the calponin content varied among different smooth muscle tissues and correlated with that of h-caldesmon. In contrast with the constitutive expression of calponin in phasic smooth muscle of the digestive tract, very low levels of calponin were detected in adult avian tracheas and no calponin expression was detected in embryonic and young chick tracheas. These results provide information on the structural conservation of calponins and suggest a relationship between calponin expression and smooth muscle functional states.Key words: smooth muscle calponin, caldesmon, expression, development, chicken trachea.

DNA in rat hepatocyte nuclei: effects of treatment with low levels of carbon tetrachloride and (or) chlordane

1979 ◽  
Vol 57 (5) ◽  
pp. 1003-1009 ◽  
Author(s):  
D. C. Mahon ◽  
K. K. Nair ◽  
P. C. Oloffs
Keyword(s):  
Liver Cirrhosis ◽  
Carbon Tetrachloride ◽  
Dna Content ◽  
Hepatic Dysfunction ◽  
Chromatin Condensation ◽  
Nuclear Size ◽  
Rat Hepatocyte ◽  
Highly Sensitive ◽  
Dna Contents ◽  
Low Levels

The effects of low-level, chronic feeding of the insecticide chlordane on the cytochemistry of the hepatocyte nuclei of male nits, with or without liver cirrhosis, were determined. Chlordane was given orally at 0.1 mg kg−1 day−1. Cirrhosis was induced by exposure of the animals to carbon tetrachloride (CCl4) vapours twice weekly for 10 weeks. The animals were killed after 20 weeks and the Feulgen-stained hepatocyte nuclei examined microspectrophotometrically for nuclear size, DNA content, and the degree of chromatin condensation. The five experimental groups were: (A) control; (B) chlordane only for 20 weeks; (C) cirrhosis only (CCl4 weeks 0–10); (D) chlordane (weeks 0–20) plus cirrhosis; (E) cirrhosis (CCl4, weeks 0–10) followed by chlordane (weeks 10–20). All treatments significantly (p < 0.01) increased nuclear size. Although DNA contents were not affected by chlordane alone, in cirrhotic animals treatment with chlordane caused significantly higher DNA contents than that in cirrhotics not receiving chlordane. This suggests that hepatic dysfunction increases the liver's sensitivity to respond to chlordane. Chromatin condensation was decreased by chlordane in both healthy and cirrhotic animals; animals with cirrhosis, but not receiving chlordane, had more condensed chromatin than the controls.The results of this study show that computer analysis of images of Feulgen-stained nuclei is a highly sensitive technique to detect the effects of chemicals on the degree of chromatin condensation even at dosage levels below the no-effect levels previously reported.

scholarly journals An updated assessment of Symbiodinium that associate with common scleractinian corals from Moorea (French Polynesia) reveals high diversity among background symbionts and a novel finding of clade B.

2016 ◽  
Author(s):  
Héloïse Rouzé ◽  
Gaël J Lecellier ◽  
Denis Saulnier ◽  
Serge Planes ◽  
Yannick Gueguen ◽  
...  
Keyword(s):  
Coral Species ◽  
French Polynesia ◽  
Molecular Tools ◽  
Quantitative Real Time Pcr ◽  
Algal Symbionts ◽  
Clade B ◽  
Highly Sensitive ◽  
Low Levels ◽  
First Time ◽  
High Diversity

The adaptative bleaching hypothesis (ABH) states that depending on the symbiotic flexibility of coral hosts (i.e., the ability of corals to “switch” or “shuffle” their algal symbionts), coral bleaching can lead to a change in the composition of their associated Symbiodinium community, and, thus, contribute to the coral’s overall survival. In order to determine the flexibility of corals, molecular tools are required to provide accurate species delineations, and to detect low levels of coral-associated Symbiodinium. Here, we used highly sensitive quantitative (real-time) PCR (qPCR) technology to analyse five common coral species from Moorea (French Polynesia), previously screened using only traditional conventional molecular methods, to assess the presence of low-abundance (background) Symbiodinium. Similar to other studies, each coral species exhibited a strong specificity to a particular clade, irrespective of the environment. In addition, however, each of the five species harboured at least one additional Symbiodinium clade, among clades A-D, at background levels. Unexpectedly, and for the first time in French Polynesia, clade B was detected as a coral symbiont. These results increase the number of known coral-Symbiodinium associations from corals found in French Polynesia, and likely indicate an underestimation of the ability of the corals in this region to associate with and/or “shuffle” different Symbiodinium clades. Altogether our data suggest that corals from French Polynesia may manage a trade-off between optimizing symbioses with a specific Symbiodinium clade(s), and maintaining associations with particular background clades that may play a role in the ability of corals to respond to environmental change.

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