scholarly journals Half-life of Ingested Antibodies in Anopheles Stephensi Mosquito Is Less Than 10 Hours

2021 ◽  
Author(s):  
Kazutoyo Miura ◽  
Deng Bingbing ◽  
Yonas T Gebremicale ◽  
Thao P Pham ◽  
Ababacar Diouf ◽  
...  
Keyword(s):  
Exponential Decay ◽  
Mechanism Of Action ◽  
Half Life ◽  
Human Monoclonal Antibody ◽  
Critical Role ◽  
Target Antigen ◽  
Multiple Time ◽  
Human Red Blood Cells ◽  
Exponential Decay Model ◽  
Multiple Time Points

Abstract Background: A transmission-blocking vaccine (TBV) can be a useful tool to reduce malaria infection in an endemic area. For a TBV, elicited antibody (either by itself or working with complement) has a critical role in the mechanism of action, which for most known TBV targets, blockade will occur within the mosquito. However, no study has quantitively assessed the longevity of ingested antibody in Anopheles mosquito vectors. Methods: A mixture of mouse or human monoclonal antibody (mAb), human red blood cells and human serum were fed to An. stephensi mosquitoes, and their midguts were collected at multiple time points (0 to 48 hours; 12 mosquitoes at each time point) after feeds. The reactivity of antibodies against target antigen (integrity of antigen-binding region of the antibody) in each midgut was assessed by ELISA. For one mouse mAb, integrity of antibody constant region was also determined by western blot (WB) with a mouse-specific secondary antibody.Results: First, the half-life of mouse anti-Pfs25 mAb, 4B7, was determined both by ELISA and WB in three independent assays. When the ELISA and WB signals were plotted against time after feed, both data reasonably fit one-phase exponential decay models (R2 B 0.70), and the half-lives were estimated as 8.6 hours by ELISA and 4.7 hours by WB. To determine whether the longevity was affected by target antigens or species of antibody, two human anti-Pfs25 mAbs (AB1245 and AB2544), one human anti-Pfs48/45 mAb (TB31F), and one mouse anti-Pfs230 mAb (15A4-1B12) were examined by ELISA in two or three independent assays. The ELISA results of each additional mAb also reasonably fit to a one-phase exponential decay model (R2 a 0.78), and the half-lives of those mAbs were similar to that of 4B7 (7.2 to 9.3 hours), except AB1245 which showed a half-life of 4.6 hours. Conclusions: Depending on the methods of detection and mAbs used, the longevity of ingested antibody varied around 2-fold, but all estimated half-lives were < 10 hours. These data suggest a TBV with antibody dependent mechanism of action(s) is more likely to succeed when targeting earlier stages of parasites (or parasite interaction) in mosquitoes.

Tree windthrow and forest soil turnover

1989 ◽  
Vol 19 (3) ◽  
pp. 386-389 ◽  
Author(s):  
D. A. Norton
Keyword(s):  
Forest Soil ◽  
Exponential Decay ◽  
Half Life ◽  
Soil Development ◽  
Turnover Time ◽  
Important Influence ◽  
Plant Distribution ◽  
Canopy Trees ◽  
Decay Model ◽  
Exponential Decay Model

Soil turnover as a result of tree windthrow has an important influence on soil development and plant distribution in forests. Estimates of the time needed for soil turnover in a given area are often made, but unless these take into account the potential for reestablishment of canopy trees onto sites previously affected by windthrow, they are likely to substantially underestimate turnover time. Soil turnover is not a regular, uniform process, but rather results in a mosaic of soils with different turnover histories. Because soil turnover follows an exponential decay model, some area of soil will never be turned over. As it is therefore not possible to define the time when all the soil in an area has been turned over, it is proposed that soil turnover half-life (the time at which half the soil has been turned over) be used as a measure of soil turnover.

scholarly journals Longitudinal Study to Assess the Quantitative Use of Fundus Autofluorescence for Monitoring Disease Progression in Choroideremia

2021 ◽  
Vol 10 (2) ◽  
pp. 232
Author(s):  
Adam M Dubis ◽  
Wei S Lim ◽  
Jasleen K Jolly ◽  
Maria Toms ◽  
Robert E MacLaren ◽  
...  
Keyword(s):  
Disease Progression ◽  
Exponential Decay ◽  
Half Life ◽  
Fundus Autofluorescence ◽  
Area Measurement ◽  
Timely Manner ◽  
Measurement Variability ◽  
Slow Progression ◽  
Exponential Decay Model

Background: Characterisation of preserved autofluorescence (PAF) area in choroideremia (CHM) and its validity for monitoring disease progression in clinical trials is of importance. Methods: Eighty patients with molecularly confirmed CHM were recruited. PAF area was measured manually by 2 graders and half-life was calculated based on exponential decay model. Results: Mean age at baseline and follow-up examination was 38.1 (range, 10–69) and 40.7 (range, 11–70) years. Mean follow-up interval was 29 months (range, 6–104). The median LogMAR visual acuity was 0.10 (OD) and 0.18 (OS). Interobserver repeatability for PAF area was −0.99 to 1.03 mm2 (−6.46 to 6.49% of area). There was a statistically significant relationship between age and rate of PAF area loss (r2 = 0.28, p = 0.012). The half-life for PAF area was 13.7 years (range, 1.7–216.0 years). The correlation between half-life and age was stronger than between half-life and log transformed baseline PAF area, although neither was statistically significant. Conclusions: The intra- and inter-observer PAF area measurement variability provides a baseline change, which must be overcome in a clinical trial if this metric were to be used. Treatments must slow progression to alter the exponential decay in a timely manner accounting for naturally slow progression patterns.

scholarly journals Using the Negative Exponential Model to Describe Changes in Risk of Smoking-Related Diseases following Changes in Exposure to Tobacco

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Peter N. Lee ◽  
John Hamling ◽  
John Fry ◽  
Barbara Forey
Keyword(s):  
Relative Risk ◽  
Half Life ◽  
Epidemiological Data ◽  
Exponential Model ◽  
Excess Relative Risk ◽  
Multiple Time ◽  
Product Switching ◽  
Negative Exponential Model ◽  
Multiple Time Points ◽  
Negative Exponential

Recently published analyses for four smoking-related diseases show that the declining excess relative risk by time quit is well fitted by the negative exponential model. These analyses estimated the half-life of this excess, that is, the time after quitting when the excess relative risk reaches half that for continuing smokers. We describe extensions of the simple model. One quantifies the decline following an exposure reduction. We show that this extension satisfactorily predicts results from studies investigating the effect of reducing cigarette consumption. It may also be relevant to exposure reductions following product-switching. Another extension predicts changes in excess relative risk occurring following multiple exposure changes over time. Suitable published epidemiological data are unavailable to test this, and we recommend its validity to be investigated using large studies with data recorded on smoking habits at multiple time points in life. The basic formulae described assume that the excess relative risk for a continuing smoker is linearly related to exposure and that the half-life is invariant of age. We describe model adaptations to allow for nonlinear dose-response and for age-dependence of the half-life. The negative exponential model, though relatively simple, appears to have many potential uses in epidemiological research for summarizing variations in risk with exposure changes.

scholarly journals Survival of LA-MRSA in Dust from Swine Farms

2018 ◽  
Vol 62 (2) ◽  
pp. 147-156 ◽  
Author(s):  
Louise Feld ◽  
Hans Bay ◽  
Øystein Angen ◽  
Anders Rhod Larsen ◽  
Anne Mette Madsen
Keyword(s):  
Staphylococcus Aureus ◽  
Exponential Decay ◽  
Half Life ◽  
Storage Time ◽  
Decay Constant ◽  
Airborne Dust ◽  
Swine Farms ◽  
Exponential Decay Model ◽  
Staphylococcus Equorum ◽  
Rate Of Decay

AbstractDust is suspected to be an important factor in transmission of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) between pigs and pig farmers and their families. The aim of this study was to determine the rate of decay for Staphylococcus aureus and LA-MRSA in dust from swine farms. Electrostatic dust fall collectors (EDCs) were used for passive sampling of settling airborne dust in 11 stable sections from six swine farms. Extraction, plating, identification, and enumeration of cultivable S. aureus and LA-MRSA from the EDCs were performed after storage for 0–30 days postsampling. The survival of S. aureus was measured in 196 dust samples from all farms, and data were used to estimate the decay constant λ according to a model for exponential decay: N(t) = N0 × e−λt. The number of S. aureus colonies was up to 600-fold higher than the number of LA-MRSA colonies on MRSA selective agar. The data showed a good fit to the model (λ = 0.13, r2 = 0.86) even with a large difference in initial concentrations of S. aureus between stables. The loads of S. aureus and LA-MRSA in the dust were significantly reduced by storage time, and the half-life was 5 days for both S. aureus and LA-MRSA. In dust samples with high initial concentrations, LA-MRSA and S. aureus could still be cultivated 30 days after sampling. On all farms MRSA isolates belonged to the clonal complex (CC) 398, and at one farm some isolates also belonged to CC30. A screening for other Staphylococcus species in the farm dust revealed 13 different species numerically dominated by Staphylococcus equorum. Based on the exponential decay model, S. equorum had a half-life of 4 days. In conclusion, the presence of MRSA in airborne dust from five of six farms indicates that dust might be an important vehicle for transmission of LA-MRSA. LA-MRSA and S. aureus was found to survive well in farm dust with half-lives of 5 days, and dependent on the initial concentration they could be found in farm dust for weeks. The 99.9% die-off rate was 66 days for LA-MRSA. Thus, farm dust can pose an exposure risk for humans in the farm environment, but also when transported to other environments. On the other hand, the risk will decrease by time. These results provide important knowledge to diminish spread from farm environments to other environments on, e.g., tools or clothing, and in relation to cleaning of emptied LA-MRSA-positive stables.

scholarly journals Physical activity levels among ovarian cancer survivors: a prospective longitudinal cohort study

2021 ◽  
pp. ijgc-2020-002107
Author(s):  
Tamara Jones ◽  
Carolina Sandler ◽  
Dimitrios Vagenas ◽  
Monika Janda ◽  
Andreas Obermair ◽  
...  
Keyword(s):  
Physical Activity ◽  
Ovarian Cancer ◽  
Stage Iv ◽  
Multiple Time ◽  
Activity Levels ◽  
Prospective Longitudinal Study ◽  
Physical Activity Advice ◽  
Physical Activity Levels ◽  
Multiple Time Points ◽  
Prospective Longitudinal

ObjectivePhysical activity following cancer diagnosis is associated with improved outcomes, including potential survival benefits, yet physical activity levels among common cancer types tend to decrease following diagnosis and remain low. Physical activity levels following diagnosis of less common cancers, such as ovarian cancer, are less known. The objectives of this study were to describe physical activity levels and to explore characteristics associated with physical activity levels in women with ovarian cancer from pre-diagnosis to 2 years post-diagnosis.MethodsAs part of a prospective longitudinal study, physical activity levels of women with ovarian cancer were assessed at multiple time points between pre-diagnosis and 2 years post-diagnosis. Physical activity levels and change in physical activity were described using metabolic equivalent task hours and minutes per week, and categorically (sedentary, insufficiently, or sufficiently active). Generalized Estimating Equations were used to explore whether participant characteristics were related to physical activity levels.ResultsA total of 110 women with ovarian cancer with a median age of 62 years (range 33–88) at diagnosis were included. 53–57% of the women were sufficiently active post-diagnosis, although average physical activity levels for the cohort were below recommended levels throughout the 2-year follow-up period (120–142.5min/week). A decrease or no change in post-diagnosis physical activity was reported by 44–60% of women compared with pre-diagnosis physical activity levels. Women diagnosed with stage IV disease, those earning a lower income, those receiving chemotherapy, and those currently smoking or working were more likely to report lower physical activity levels and had increased odds of being insufficiently active or sedentary.ConclusionsInterventions providing patients with appropriate physical activity advice and support for behavior change could potentially improve physical activity levels and health outcomes.

scholarly journals The molecular make up of smoldering myeloma highlights the evolutionary pathways leading to multiple myeloma

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Eileen M. Boyle ◽  
Shayu Deshpande ◽  
Ruslana Tytarenko ◽  
Cody Ashby ◽  
Yan Wang ◽  
...  
Keyword(s):  
Tumour Suppressor Genes ◽  
Multiple Time ◽  
Clonal Structure ◽  
Time To Progression ◽  
Novel Mutations ◽  
Evolutionary Patterns ◽  
Risk Of Progression ◽  
Multiple Time Points ◽  
Smoldering Myeloma ◽  
Copy Number Changes

AbstractSmoldering myeloma (SMM) is associated with a high-risk of progression to myeloma (MM). We report the results of a study of 82 patients with both targeted sequencing that included a capture of the immunoglobulin and MYC regions. By comparing these results to newly diagnosed myeloma (MM) we show fewer NRAS and FAM46C mutations together with fewer adverse translocations, del(1p), del(14q), del(16q), and del(17p) in SMM consistent with their role as drivers of the transition to MM. KRAS mutations are associated with a shorter time to progression (HR 3.5 (1.5–8.1), p = 0.001). In an analysis of change in clonal structure over time we studied 53 samples from nine patients at multiple time points. Branching evolutionary patterns, novel mutations, biallelic hits in crucial tumour suppressor genes, and segmental copy number changes are key mechanisms underlying the transition to MM, which can precede progression and be used to guide early intervention strategies.

scholarly journals Use of TanDEM-X and SRTM-C Data for Detection of Deforestation Caused by Bark Beetle in Central European Mountains

2021 ◽  
Vol 13 (15) ◽  
pp. 3042
Author(s):  
Kateřina Gdulová ◽  
Jana Marešová ◽  
Vojtěch Barták ◽  
Marta Szostak ◽  
Jaroslav Červenka ◽  
...  
Keyword(s):  
Bark Beetle ◽  
Synergistic Effects ◽  
Canopy Height ◽  
Surface Model ◽  
Multiple Time ◽  
Central European ◽  
Time Points ◽  
Bohemian Forest ◽  
Multiple Time Points ◽  
Surrounding Areas

The availability of global digital elevation models (DEMs) from multiple time points allows their combination for analysing vegetation changes. The combination of models (e.g., SRTM and TanDEM-X) can contain errors, which can, due to their synergistic effects, yield incorrect results. We used a high-resolution LiDAR-derived digital surface model (DSM) to evaluate the accuracy of canopy height estimates of the aforementioned global DEMs. In addition, we subtracted SRTM and TanDEM-X data at 90 and 30 m resolutions, respectively, to detect deforestation caused by bark beetle disturbance and evaluated the associations of their difference with terrain characteristics. The study areas covered three Central European mountain ranges and their surrounding areas: Bohemian Forest, Erzgebirge, and Giant Mountains. We found that vertical bias of SRTM and TanDEM-X, relative to the canopy height, is similar with negative values of up to −2.5 m and LE90s below 7.8 m in non-forest areas. In forests, the vertical bias of SRTM and TanDEM-X ranged from −0.5 to 4.1 m and LE90s from 7.2 to 11.0 m, respectively. The height differences between SRTM and TanDEM-X show moderate dependence on the slope and its orientation. LE90s for TDX-SRTM differences tended to be smaller for east-facing than for west-facing slopes, and varied, with aspect, by up to 1.5 m in non-forest areas and 3 m in forests, respectively. Finally, subtracting SRTM and NASA DEMs from TanDEM-X and Copernicus DEMs, respectively, successfully identified large areas of deforestation caused by hurricane Kyril in 2007 and a subsequent bark beetle disturbance in the Bohemian Forest. However, local errors in TanDEM-X, associated mainly with forest-covered west-facing slopes, resulted in erroneous identification of deforestation. Therefore, caution is needed when combining SRTM and TanDEM-X data in multitemporal studies in a mountain environment. Still, we can conclude that SRTM and TanDEM-X data represent suitable near global sources for the identification of deforestation in the period between the time points of their acquisition.

scholarly journals Associations of Binge Drinking With Vascular Brain Injury and Atrophy in Older American Indians: The Strong Heart Study

2021 ◽  
Vol 33 (7-8_suppl) ◽  
pp. 51S-59S
Author(s):  
Jordan P. Lewis ◽  
Astrid M. Suchy-Dicey ◽  
Carolyn Noonan ◽  
Valarie Blue Bird Jernigan ◽  
Jason G. Umans ◽  
...  
Keyword(s):  
Brain Injury ◽  
Binge Drinking ◽  
American Indians ◽  
Multiple Time ◽  
Heart Study ◽  
Neurological Risk ◽  
The Us ◽  
Large Cohort Study ◽  
Magnetic Resonance Imaging Mri ◽  
Multiple Time Points

Objectives: American Indians (AIs) generally consume less alcohol than the US general population; however, the prevalence of alcohol use disorder is higher. This is the first large cohort study to examine binge drinking as a risk factor for vascular brain injury (VBI). Methods: We used linear and Poisson regression to examine the association of self-reported binge drinking with VBI, measured via magnetic resonance imaging (MRI), in 817 older AIs who participated in the Strong Heart and Cerebrovascular Disease and Its Consequences in American Indians studies. Results: Any binge drinking at multiple time-points was associated with increased sulcal (β = 0.360, 95% CI [0.079, 0.641]) and ventricle dilatation (β = 0.512, 95% CI [0.174, 0.850]) compared to no binge drinking. Discussion: These observed associations are consistent with previous findings. Identifying how binge drinking may contribute to VBI in older AIs may suggest modifiable health behaviors for neurological risk reduction and disease prevention.

scholarly journals Inferring time series chromatin states for promoter-enhancer pairs based on Hi-C data

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Henriette Miko ◽  
Yunjiang Qiu ◽  
Bjoern Gaertner ◽  
Maike Sander ◽  
Uwe Ohler
Keyword(s):  
Time Series ◽  
Histone Modifications ◽  
Gene Activation ◽  
Expectation Maximization Algorithm ◽  
Chromatin State ◽  
Open Chromatin ◽  
Multiple Time ◽  
Enhancer Activity ◽  
Chromatin States ◽  
Multiple Time Points

Abstract Background Co-localized combinations of histone modifications (“chromatin states”) have been shown to correlate with promoter and enhancer activity. Changes in chromatin states over multiple time points (“chromatin state trajectories”) have previously been analyzed at promoter and enhancers separately. With the advent of time series Hi-C data it is now possible to connect promoters and enhancers and to analyze chromatin state trajectories at promoter-enhancer pairs. Results We present TimelessFlex, a framework for investigating chromatin state trajectories at promoters and enhancers and at promoter-enhancer pairs based on Hi-C information. TimelessFlex extends our previous approach Timeless, a Bayesian network for clustering multiple histone modification data sets at promoter and enhancer feature regions. We utilize time series ATAC-seq data measuring open chromatin to define promoters and enhancer candidates. We developed an expectation-maximization algorithm to assign promoters and enhancers to each other based on Hi-C interactions and jointly cluster their feature regions into paired chromatin state trajectories. We find jointly clustered promoter-enhancer pairs showing the same activation patterns on both sides but with a stronger trend at the enhancer side. While the promoter side remains accessible across the time series, the enhancer side becomes dynamically more open towards the gene activation time point. Promoter cluster patterns show strong correlations with gene expression signals, whereas Hi-C signals get only slightly stronger towards activation. The code of the framework is available at https://github.com/henriettemiko/TimelessFlex. Conclusions TimelessFlex clusters time series histone modifications at promoter-enhancer pairs based on Hi-C and it can identify distinct chromatin states at promoter and enhancer feature regions and their changes over time.

scholarly journals Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidates for targeted treatment

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hua Sun ◽  
Song Cao ◽  
R. Jay Mashl ◽  
Chia-Kuei Mo ◽  
Simone Zaccaria ◽  
...  
Keyword(s):  
Human Tumors ◽  
Multiple Time ◽  
Cancer Treatments ◽  
Whole Genome Duplications ◽  
Patient Derived Xenograft ◽  
Genome Duplications ◽  
Genomic Characterization ◽  
Cancer Types ◽  
Multiple Time Points ◽  
Pdx Models

AbstractDevelopment of candidate cancer treatments is a resource-intensive process, with the research community continuing to investigate options beyond static genomic characterization. Toward this goal, we have established the genomic landscapes of 536 patient-derived xenograft (PDX) models across 25 cancer types, together with mutation, copy number, fusion, transcriptomic profiles, and NCI-MATCH arms. Compared with human tumors, PDXs typically have higher purity and fit to investigate dynamic driver events and molecular properties via multiple time points from same case PDXs. Here, we report on dynamic genomic landscapes and pharmacogenomic associations, including associations between activating oncogenic events and drugs, correlations between whole-genome duplications and subclone events, and the potential PDX models for NCI-MATCH trials. Lastly, we provide a web portal having comprehensive pan-cancer PDX genomic profiles and source code to facilitate identification of more druggable events and further insights into PDXs’ recapitulation of human tumors.

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