Informative Group Testing for Multiplex Assays

Infectious disease testing frequently takes advantage of two tools–group testing and multiplex assays–to make testing timely and cost effective. Until the work of Tebbs et al. (2013) and Hou et al. (2017), there was no research available to understand how best to apply these tools simultaneously. This recent work focused on applications where each individual is considered to be identical in terms of the probability of disease. However, risk-factor information, such as past behavior and presence of symptoms, is very often available on each individual to allow one to estimate individual-specific probabilities. The purpose of our paper is to propose the first group testing algorithms for multiplex assays that take advantage of individual risk-factor information as expressed by these probabilities. We show that our methods significantly reduce the number of tests required while preserving accuracy. Throughout this paper, we focus on applying our methods with the Aptima Combo 2 Assay that is used worldwide for chlamydia and gonorrhea screening

Estimating the prevalence of two or more diseases using outcomes from multiplex group testing

When screening a population for infectious diseases, pooling individual specimens (e.g., blood, swabs, urine, etc.) can provide enormous cost savings when compared to testing specimens individually. In the biostatistics literature, testing pools of specimens is commonly known as group testing or pooled testing. Although estimating a population-level prevalence with group testing data has received a large amount of attention, most of this work has focused on applications involving a single disease, such as human immunodeficiency virus. Modern methods of screening now involve testing pools and individuals for multiple diseases simultaneously through the use of multiplex assays. Hou et al. (2017, Biometrics, 73, 656–665) and Hou et al. (2020, Biostatistics, 21, 417–431) recently proposed group testing protocols for multiplex assays and derived relevant case identification characteristics, including the expected number of tests and those which quantify classification accuracy. In this article, we describe Bayesian methods to estimate population-level disease probabilities from implementing these protocols or any other multiplex group testing protocol which might be carried out in practice. Our estimation methods can be used with multiplex assays for two or more diseases while incorporating the possibility of test misclassification for each disease. We use chlamydia and gonorrhea testing data collected at the State Hygienic Laboratory at the University of Iowa to illustrate our work. We also provide an online R resource practitioners can use to implement the methods in this article

The approach to vortex reconnection

We present numerical solutions of the Gross--Pitaevskii equation corresponding to reconnecting vortex lines. We determine the separation of vortices as a function of time during the approach to reconnection, and study the formation of pyramidal vortex structures. Results are compared with analytical work and numerical studies based on the vortex filament method.Comment: 11 pages, 9 figure

The Initial Step in Human Immunodeficiency Virus Type 1 GagProPol Processing Can Be Regulated by Reversible Oxidation

BACKGROUND: Maturation of human immunodeficiency virus type 1 (HIV-1) occurs upon activation of HIV-1 protease embedded within GagProPol precursors and cleavage of Gag and GagProPol polyproteins. Although reversible oxidation can regulate mature protease activity as well as retrovirus maturation, it is possible that the effects of oxidation on viral maturation are mediated in whole, or part, through effects on the initial intramolecular cleavage event of GagProPol. In order assess the effect of reversible oxidation on this event, we developed a system to isolate the first step in protease activation involving GagProPol. METHODOLOGY/PRINCIPAL FINDINGS: To determine if oxidation influences this step, we created a GagProPol plasmid construct (pGPfs-1C) that encoded mutations at all cleavage sites except p2/NC, the initial cleavage site in GagProPol. pGPfs-1C was used in an in vitro translation assay to observe the behavior of this initial step without interference from subsequent processing events. Diamide, a sulfhydral oxidizing agent, inhibited processing at p2/NC by >60% for pGPfs-1C and was readily reversed with the reductant, dithiothreitol. The ability to regulate processing by reversible oxidation was lost when the cysteines of the embedded protease were mutated to alanine. Unlike mature protease, which requires only oxidation of cys95 for inhibition, both cysteines of the embedded protease contributed to this inhibition. CONCLUSIONS/SIGNIFICANCE: We developed a system that can be used to study the first step in the cascade of HIV-1 GagProPol processing and show that reversible oxidation of cysteines of HIV-1 protease embedded in GagProPol can block this initial GagProPol autoprocessing. This type of regulation may be broadly applied to the majority of retroviruses

Regional-scale high spatial resolution mapping of aboveground net primary productivity (ANPP) from field survey and Landsat data: a case study for the country of Wales

This paper presents an alternative approach for high spatial resolution vegetation productivity mapping at a regional scale, using a combination of Normalised Difference Vegetation Index (NDVI) imagery and widely distributed ground-based Above-ground Net Primary Production (ANPP) estimates. Our method searches through all available single-date NDVI imagery to identify the images which give the best NDVI–ANPP relationship. The derived relationships are then used to predict ANPP values outside of field survey plots. This approach enables the use of the high spatial resolution (30 m) Landsat 8 sensor, despite its low revisit frequency that is further reduced by cloud cover. This is one of few studies to investigate the NDVI–ANPP relationship across a wide range of temperate habitats and strong relationships were observed (R2 = 0.706), which increased when only grasslands were considered (R2 = 0.833). The strongest NDVI–ANPP relationships occurred during the spring “green-up” period. A reserved subset of 20% of ground-based ANPP estimates was used for validation and results showed that our method was able to estimate ANPP with a RMSE of 15–21%. This work is important because we demonstrate a general methodological framework for mapping of ANPP from local to regional scales, with the potential to be applied to any temperate ecosystems with a pronounced green up period. Our approach allows spatial extrapolation outside of field survey plots to produce a continuous surface product, useful for capturing spatial patterns and representing small-scale heterogeneity, and well-suited for modelling applications. The data requirements for implementing this approach are also discussed

XRCC1 haploinsufficiency in mice has little effect on aging, but adversely modifies exposure-dependent susceptibility

Oxidative DNA damage plays a role in disease development and the aging process. A prominent participant in orchestrating the repair of oxidative DNA damage, particularly single-strand breaks, is the scaffold protein XRCC1. A series of chronological and biological aging parameters in XRCC1 heterozygous (HZ) mice were examined. HZ and wild-type (WT) C57BL/6 mice exhibit a similar median lifespan of ~26 months and a nearly identical maximal life expectancy of ~37 months. However, a number of HZ animals (7 of 92) showed a propensity for abdominal organ rupture, which may stem from developmental abnormalities given the prominent role of XRCC1 in endoderm and mesoderm formation. For other end-points evaluated—weight, fat composition, blood chemistries, condition of major organs, tissues and relevant cell types, behavior, brain volume and function, and chromosome and telomere integrity—HZ mice exhibited by-and-large a normal phenotype. Treatment of animals with the alkylating agent azoxymethane resulted in both liver toxicity and an increased incidence of precancerous lesions in the colon of HZ mice. Our study indicates that XRCC1 haploinsufficiency in mammals has little effect on chronological longevity and many key biological markers of aging in the absence of environmental challenges, but may adversely affect normal animal development or increase disease susceptibility to a relevant genotoxic exposure

XRCC1 haploinsufficiency in mice has little effect on aging, but adversely modifies exposure-dependent susceptibility

Oxidative DNA damage plays a role in disease development and the aging process. A prominent participant in orchestrating the repair of oxidative DNA damage, particularly single-strand breaks, is the scaffold protein XRCC1. A series of chronological and biological aging parameters in XRCC1 heterozygous (HZ) mice were examined. HZ and wild-type (WT) C57BL/6 mice exhibit a similar median lifespan of ~26 months and a nearly identical maximal life expectancy of ~37 months. However, a number of HZ animals (7 of 92) showed a propensity for abdominal organ rupture, which may stem from developmental abnormalities given the prominent role of XRCC1 in endoderm and mesoderm formation. For other end-points evaluated—weight, fat composition, blood chemistries, condition of major organs, tissues and relevant cell types, behavior, brain volume and function, and chromosome and telomere integrity—HZ mice exhibited by-and-large a normal phenotype. Treatment of animals with the alkylating agent azoxymethane resulted in both liver toxicity and an increased incidence of precancerous lesions in the colon of HZ mice. Our study indicates that XRCC1 haploinsufficiency in mammals has little effect on chronological longevity and many key biological markers of aging in the absence of environmental challenges, but may adversely affect normal animal development or increase disease susceptibility to a relevant genotoxic exposure

The sensitivity of the vortex filament method to different reconnection models

We present a detailed analysis on the effect of using different algorithms to model the reconnection of vortices in quantum turbulence, using the thin-filament approach. We examine differences between four main algorithms for the case of turbulence driven by a counterflow. In calculating the velocity field we use both the local induction approximation (LIA) and the full Biot-Savart integral. We show that results of Biot-Savart simulations are not sensitive to the particular reconnection method used, but LIA results are.Comment: 9 pages, 9 figure

A simple graphical way of evaluating coverage and directional non-coverages

Evaluation of the coverage probability and, more recently, of the intervalar location of con dence intervals, is a useful procedure if exact and asymptotic methods for constructing con dence intervals are used for some populacional parameter. In this paper, a simple graphical procedure is presented to execute this kind of evaluation in con dence methods for linear combinations of k independent binomial proportions. Our proposal is based on the representation of the mesial and distal non-coverage probabilities on a plane. We carry out a simulation study to show how this graphical representation can be interpreted and used as a basis for the evaluation of intervalar location of con dence interval methods

Axisymmetric infiltration

The work reported herein was performed under the annual allotment from the Office of Water Resources Research to the Oregon Water Resources Research Institute. Funds were available over a three year period, but due to difficulty in acquiring graduate students, the total time spent on the project was only 21 months