50 research outputs found
Flow cytometric measurement of STAT5 phosphorylation in cytomegalovirus-stimulated T cells
Cytomegalovirus (CMV)-specific T cells expand with CMV reactivation and are probably prerequisite for control and protection. Given the critical role STAT5A phosphorylation (pSTAT5A) in T cell proliferation, this study presents a simple and sensitive flow cytometric-based pSTAT5A assay to quickly identify CMV-specific T cell proliferation. We determined pSTAT5A in T cells treated with CMV-specific peptide mix (pp65 + IE1 peptides) from 20 healthy adult subjects and three immunodeficient patients with CARMIL-2 mutation. After stimulation, the percentage of pSTAT5A+ T cells in CMV-seropositive (CMV+) subjects significantly increased from 3.0% ± 1.9% (unstimulated) to 11.4% ± 5.9% (stimulated) for 24 h. After 7 days of stimulation, the percentage of expanded T cells amounted to 26% ± 17.2%. Conversely, the percentage of pSTAT5A+ T cells and T cell proliferation from CMV-seronegative (CMV−) subjects hardly changed (from 3.0% ± 1.3% to 3.7% ± 1.8% and from 4.3% ± 2.1% to 5.7% ± 1.7%, respectively). We analyzed the correlation between the percentage of pSTAT5A+ T cells versus (1) CMV-IgG concentrations versus (2) the percentage of expanded T cells and versus (3) the percentage of initial CMV-specific T cells. In immunodeficient patients with CARMIL-2 mutation, CMV-specific pSTAT5A and T cell proliferation were completely deficient. In conclusion, flow cytometric-based pSTAT5A assay represents an appropriate tool to quickly identify CMV-specific T cell proliferation and helps to understand dysfunctions in controlling other pathogens. Flow cytometric-based pSTAT5A assay may be a useful test in clinical practice and merits further validation in large studies
Designing Future Dark Energy Space Missions: II. Photometric Redshift of Space Weak Lensing Optimized Survey
Accurate weak-lensing analysis requires not only accurate measurement of
galaxy shapes but also precise and unbiased measurement of galaxy redshifts.
The photometric redshift technique appears as the only possibility to determine
the redshift of the background galaxies used in the weak-lensing analysis.
Using the photometric redshift quality, simple shape measurement requirements,
and a proper sky model, we explore what could be an optimal weak-lensing dark
energy mission based on FoM calculation. We found that photometric redshifts
reach their best accuracy for the bulk of the faint galaxy population when
filters have a resolution R~3.2. We show that an optimal mission would survey
the sky through 8 filters using 2 cameras (visible and near infrared). Assuming
a 5-year mission duration, a mirror size of 1.5m, a 0.5deg2 FOV with a visible
pixel scale of 0.15", we found that a homogeneous survey reaching IAB=25.6
(10sigma) with a sky coverage of ~11000deg2 maximizes the Weak Lensing FoM. The
effective number density of galaxies then used for WL is ~45gal/arcmin2, at
least a factor of two better than ground based survey. This work demonstrates
that a full account of the observational strategy is required to properly
optimize the instrument parameters to maximize the FoM of the future
weak-lensing space dark energy mission.Comment: 25 pages, 39 figures, accepted in A&
Dealing with missing standard deviation and mean values in meta-analysis of continuous outcomes: a systematic review
Background: Rigorous, informative meta-analyses rely on availability of appropriate summary statistics or individual
participant data. For continuous outcomes, especially those with naturally skewed distributions, summary
information on the mean or variability often goes unreported. While full reporting of original trial data is the ideal,
we sought to identify methods for handling unreported mean or variability summary statistics in meta-analysis.
Methods: We undertook two systematic literature reviews to identify methodological approaches used to deal with
missing mean or variability summary statistics. Five electronic databases were searched, in addition to the Cochrane
Colloquium abstract books and the Cochrane Statistics Methods Group mailing list archive. We also conducted cited
reference searching and emailed topic experts to identify recent methodological developments. Details recorded
included the description of the method, the information required to implement the method, any underlying
assumptions and whether the method could be readily applied in standard statistical software. We provided a
summary description of the methods identified, illustrating selected methods in example meta-analysis scenarios.
Results: For missing standard deviations (SDs), following screening of 503 articles, fifteen methods were identified in
addition to those reported in a previous review. These included Bayesian hierarchical modelling at the meta-analysis
level; summary statistic level imputation based on observed SD values from other trials in the meta-analysis; a practical
approximation based on the range; and algebraic estimation of the SD based on other summary statistics. Following
screening of 1124 articles for methods estimating the mean, one approximate Bayesian computation approach and
three papers based on alternative summary statistics were identified. Illustrative meta-analyses showed that when
replacing a missing SD the approximation using the range minimised loss of precision and generally performed better
than omitting trials. When estimating missing means, a formula using the median, lower quartile and upper quartile
performed best in preserving the precision of the meta-analysis findings, although in some scenarios, omitting trials
gave superior results.
Conclusions: Methods based on summary statistics (minimum, maximum, lower quartile, upper quartile, median)
reported in the literature facilitate more comprehensive inclusion of randomised controlled trials with missing mean or
variability summary statistics within meta-analyses
Vascular clamping in liver surgery: physiology, indications and techniques
This article reviews the historical evolution of hepatic vascular clamping and their indications. The anatomic basis for partial and complete vascular clamping will be discussed, as will the rationales of continuous and intermittent vascular clamping
A Roadmap for HEP Software and Computing R&D for the 2020s
Particle physics has an ambitious and broad experimental programme for the coming decades. This programme requires large investments in detector hardware, either to build new facilities and experiments, or to upgrade existing ones. Similarly, it requires commensurate investment in the R&D of software to acquire, manage, process, and analyse the shear amounts of data to be recorded. In planning for the HL-LHC in particular, it is critical that all of the collaborating stakeholders agree on the software goals and priorities, and that the efforts complement each other. In this spirit, this white paper describes the R&D activities required to prepare for this software upgrade.Peer reviewe
Flow cytometric measurement of STAT5 phosphorylation in cytomegalovirus-stimulated T cells
Cytomegalovirus (CMV)-specific T cells expand with CMV reactivation and are probably prerequisite for control and protection. Given the critical role STAT5A phosphorylation (pSTAT5A) in T cell proliferation, this study presents a simple and sensitive flow cytometric-based pSTAT5A assay to quickly identify CMV-specific T cell proliferation. We determined pSTAT5A in T cells treated with CMV-specific peptide mix (pp65 + IE1 peptides) from 20 healthy adult subjects and three immunodeficient patients with CARMIL-2 mutation. After stimulation, the percentage of pSTAT5A+ T cells in CMV-seropositive (CMV+) subjects significantly increased from 3.0% ± 1.9% (unstimulated) to 11.4% ± 5.9% (stimulated) for 24 h. After 7 days of stimulation, the percentage of expanded T cells amounted to 26% ± 17.2%. Conversely, the percentage of pSTAT5A+ T cells and T cell proliferation from CMV-seronegative (CMV−) subjects hardly changed (from 3.0% ± 1.3% to 3.7% ± 1.8% and from 4.3% ± 2.1% to 5.7% ± 1.7%, respectively). We analyzed the correlation between the percentage of pSTAT5A+ T cells versus (1) CMV-IgG concentrations versus (2) the percentage of expanded T cells and versus (3) the percentage of initial CMV-specific T cells. In immunodeficient patients with CARMIL-2 mutation, CMV-specific pSTAT5A and T cell proliferation were completely deficient. In conclusion, flow cytometric-based pSTAT5A assay represents an appropriate tool to quickly identify CMV-specific T cell proliferation and helps to understand dysfunctions in controlling other pathogens. Flow cytometric-based pSTAT5A assay may be a useful test in clinical practice and merits further validation in large studies