Stability of plasma metabolomics over 10 years among women

Background: In epidemiological studies, samples are often collected long before disease onset or outcome assessment. Understanding the long-term stability of biomarkers measured in these samples is crucial. We estimated within-person stability over 10 years of metabolites and metabolite features (N=5938) in the Nurses' Health Study (NHS): The primary dataset included 1880 women with 1184 repeated samples donated 10 years apart while the secondary dataset included 1456 women with 488 repeated samples donated 10 years apart. Methods: We quantified plasma metabolomics using two liquid chromatography mass spectrometry platforms (lipids and polar metabolites) at the Broad Institute (Cambridge, MA). Intra-class correlations were used to estimate long-term stability (10 years) of metabolites and were calculated as the proportion of the total variability (within-person + between-person) attributable to between-person variability. Within-person variability was estimated among participants who donated two blood samples approximately 10 years apart while between-person variability was estimated among all participants. Results: In the primary dataset, the median ICC was 0.43 (1st quartile [Q1]: 0.36; 3rd quartile [Q3]: 0.50) among known metabolites and 0.41 (Q1: 0.34; Q3: 0.48) among unknown metabolite features. The most stable (median ICCs: 0.54-0.57) metabolite classes were nucleosides, nucleotides and analogues, phosphatidylcholine plasmalogens, diglycerides, and cholesteryl esters. The least stable (median ICCs: 0.26-0.36) metabolite classes were lysophosphatidylethanolamines, lysophosphatidylcholines and steroid and steroid derivatives. Results in the secondary dataset were similar (Spearman correlation=0.87) to corresponding results in the primary dataset. Conclusion: Within-person stability over 10 years is reasonable for lipid, lipid-related, and polar metabolites, and varies by metabolite class. Additional studies are required to estimate within-person stability over 10 years of other metabolites groups.

Time-lapse seismic data reconstruction using compressive sensing

The time-lapse seismic method plays a critical role in the reservoir monitoring and characterization. However, time-lapse data acquisitions are costly. Sparse acquisitions combined with post-acquisition data reconstruction could reduce the cost and facilitate more frequent applications of the time-lapse seismic monitoring. We present a sparse time-lapse seismic data reconstruction methodology based on compressive sensing. The method works with a hybrid of repeated and non-repeated sample locations. To make use of the additional information from non-repeated locations, we present a view that non-repeated samples in space are equivalent to irregular samples in calendar time. Therefore, we use these irregular samples in time coming from non-repeated samples in space to improve the performance of compressive sensing reconstruction. The tests on synthetic and field datasets indicate that our method can achieve a sufficiently accurate reconstruction by using as few as 10% of the receivers or traces. The method not only works with spatially irregular sampling for dealing with the land accessibility problem and for reducing the number of nodal sensors, but also utilizes the non-repeated measurements to improve the reconstruction accuracy.

REal-time Assessment of Community Transmission (REACT) of SARS-CoV-2 virus: Study protocol

Background: England, UK has one of the highest rates of confirmed COVID-19 mortality globally. Until recently, testing for the SARS-CoV-2 virus focused mainly on healthcare and care home settings. As such, there is far less understanding of community transmission. Protocol: The REal-time Assessment of Community Transmission (REACT) programme is a major programme of home testing for COVID-19 to track progress of the infection in the community. REACT-1 involves cross-sectional surveys of viral detection (virological swab for RT-PCR) tests in repeated samples of 100,000 to 150,000 randomly selected individuals across England. This examines how widely the virus has spread and how many people are currently infected. The age range is 5 years and above. Individuals are sampled from the England NHS patient list. REACT-2 is a series of five sub-studies towards establishing the seroprevalence of antibodies to SARS-CoV-2 in England as an indicator of historical infection. The main study (study 5) uses the same design and sampling approach as REACT-1 using a self-administered lateral flow immunoassay (LFIA) test for IgG antibodies in repeated samples of 100,000 to 200,000 adults aged 18 years and above. To inform study 5, studies 1-4 evaluate performance characteristics of SARS-CoV-2 LFIAs (study 1) and different aspects of feasibility, usability and application of LFIAs for home-based testing in different populations (studies 2-4). Ethics and dissemination: The study has ethical approval. Results are reported using STROBE guidelines and disseminated through reports to public health bodies, presentations at scientific meetings and open access publications. Conclusions: This study provides robust estimates of the prevalence of both virus (RT-PCR, REACT-1) and seroprevalence (antibody, REACT-2) in the general population in England. We also explore acceptability and usability of LFIAs for self-administered testing for SARS-CoV-2 antibody in a home-based setting, not done before at such scale in the general population.

REal-time Assessment of Community Transmission (REACT) of SARS-CoV-2 virus: Study protocol

Background: England, UK has one of the highest rates of confirmed COVID-19 mortality globally. Until recently, testing for the SARS-CoV-2 virus focused mainly on healthcare and care home settings. As such, there is far less understanding of community transmission. Protocol: The REal-time Assessment of Community Transmission (REACT) programme is a major programme of home testing for COVID-19 to track progress of the infection in the community. REACT-1 involves cross-sectional surveys of viral detection (virological swab for RT-PCR) tests in repeated samples of 100,000 to 150,000 randomly selected individuals across England. This examines how widely the virus has spread and how many people are currently infected. The age range is 5 years and above. Individuals are sampled from the England NHS patient list. REACT-2 is a series of five sub-studies towards establishing the seroprevalence of antibodies to SARS-CoV-2 in England as an indicator of historical infection. The main study (study 5) uses the same design and sampling approach as REACT-1 using a self-administered lateral flow immunoassay (LFIA) test for IgG antibodies in repeated samples of 100,000 to 200,000 adults aged 18 years and above. To inform study 5, studies 1-4 evaluate performance characteristics of SARS-CoV-2 LFIAs (study 1) and different aspects of feasibility, usability and application of LFIAs for home-based testing in different populations (studies 2-4). Ethics and dissemination: The study has ethical approval. Results are reported using STROBE guidelines and disseminated through reports to public health bodies, presentations at scientific meetings and open access publications. Conclusions: This study provides robust estimates of the prevalence of both virus (RT-PCR, REACT-1) and seroprevalence (antibody, REACT-2) in the general population in England. We also explore acceptability and usability of LFIAs for self-administered testing for SARS-CoV-2 antibody in a home-based setting, not done before at such scale in the general population.

Giving Birth to Inferential Reasoning

Too often, statistical inference and probability are treated in schools like they are unrelated. In this paper, we describe how we supported students to learn about the role of probability in making inferences with variable data by building models of real world events and using them to simulate repeated samples.

A Procedure for Estimating the Variance of the Population Mean in Rejective Sampling

Rejective sampling was first introduced by Hájek in 1964 as a way to select a sample consisting uniquely of distinct units. If n denotes the fixed sample size, the n units are drawn independently with probabilities that may vary from unit to unit and the samples in which all units are not distinct are rejected. More generally, in rejective sampling, we select repeated samples according to a basic sampling design until a selected sample meets a specified balancing tolerance. Given a set of auxiliary variables, we consider a procedure in which the probability sample is rejected unless the sample mean of the auxiliary variables is within a specified distance of its corresponding population mean. The procedure represents an alternative to the well-known balanced cube method. In this article, we propose an estimator of the variance under the rejective sampling design. We also present the results of a Monte Carlo simulation study.

The Lectin Pathway of Complement Activation in Patients with Systemic Lupus Erythematosus

Objective.The pathogenesis of systemic lupus erythematosus (SLE) involves complement activation. Activation of complement through the classical pathway (CP) is well established. However, complement activation through pattern recognition not only happens through the CP, but also through the lectin pathway (LP). We investigated the hypothesis that the LP is activated in SLE and involved in the pathogenesis of the disease.Methods.Using immunoassays developed in-house, we measured concentrations of LP proteins in a cohort of 372 patients with SLE and 170 controls. We estimated complement activation measuring total C3, and investigated whether LP protein concentrations were associated with complement activation and disease activity. Protein changes and disease activity over time were assessed in a cohort of 52 patients with SLE followed with repeated samples over a 5-year period.Results.Concentrations of LP proteins in SLE were altered compared with controls. The differences observed in LP proteins associated with complement activation were reflected by a decrease in total C3. The pattern recognition molecules (M-ficolin, CL-L1, and CL-K1), the serine protease (MASP-3), and the associated protein (MAp19) displayed a negative correlation with disease activity. Changes in MASP-2 concentrations over time correlated significantly with increased disease activity. Association between active proteinuria and serum concentration was observed for MASP-3 and MAp19.Conclusion.In patients with SLE, we measured specific changes in LP proteins that are associated with complement activation and disease activity, indicating that the LP is activated in patients with SLE. These novel findings substantiate the involvement of the LP in SLE.