Physical soil quality indicators for monitoring British soils

The condition or quality of soils determines its ability to deliver a range of functions that support ecosystem services, human health and wellbeing. The increasing policy imperative to implement successful soil monitoring programmes has resulted in the demand for reliable soil quality indicators (SQIs) for physical, biological and chemical soil properties. The selection of these indicators needs to ensure that they are sensitive and responsive to pressure and change e.g. they change across space and time in relation to natural perturbations and land management practices. Using a logical sieve approach based on key policy-related soil functions, this research assessed whether physical soil properties can be used to indicate the quality of British soils in terms of its capacity to deliver ecosystem goods and services. The resultant prioritised list of physical SQIs were tested for robustness, spatial and temporal variability and expected rate of change using statistical analysis and modelling. Six SQIs were prioritised; packing density, soil water retention characteristics, aggregate stability, rate of erosion, depth of soil and soil sealing. These all have direct relevance to current and likely future soil and environmental policy and are appropriate for implementation in soil monitoring programs

Neural network based damage detection using substructure technique

Many researchers have been studying the feasibility of using Artificial Neural Networks (ANN) in structural health monitoring and damage detection. It has been proven by both numerical simulation and laboratory test data that ANN can give reliable prediction of structural conditions. The main drawback of using ANN in structural condition monitoring is the requirement of enormous computational effort. Consequently almost all the previous work described in the literature limited the structural members to a small number of large elements in the ANN model. This may result in the ANN model being insensitive to local damage, especially when this local damage is small. To overcome this problem, this study presents an approach to detect small structural damage by using ANN progressively. It uses the substructure technique together with a two-stage ANN to detect the location and extent of the damage. It starts by dividing the structure into a few substructures. The condition of each substructure is examined. Those substructures with condition change identified are further subdivided and their condition examined. By doing this progressively, the location and severity of low level structural damage can be detected. Modal parameters such as frequencies and mode shapes are used as the input to the ANN. To demonstrate the effectiveness of this approach, a two-span continuous concrete slab structure is used as an example. Different damage scenarios are introduced by reducing the local stiffness of the selected elements at different locations along the structure. The results show that this technique successfully detects simulated damage in the structure

Second trimester serum tests for Down's Syndrome screening

Background Down's syndrome occurs when a person has three copies of chromosome 21 - or the specific area of chromosome 21 implicated in causing Down's syndrome - rather than two. It is the commonest congenital cause of mental retardation. Noninvasive screening based on biochemical analysis of maternal serum or urine, or fetal ultrasound measurements, allows estimates of the risk of a pregnancy being affected and provides information to guide decisions about definitive testing. Objectives To estimate and compare the accuracy of second trimester serum markers for the detection of Down’s syndrome. Search methods We carried out a sensitive and comprehensive literature search of MEDLINE (1980 to May 2007), EMBASE (1980 to 18 May 2007), BIOSIS via EDINA (1985 to 18 May 2007), CINAHL via OVID (1982 to 18 May 2007), The Database of Abstracts of Reviews of Effectiveness (The Cochrane Library 2007, Issue 1), MEDION (May 2007), The Database of Systematic Reviews and Meta-Analyses in Laboratory Medicine (May 2007), The National Research Register (May 2007), Health Services Research Projects in Progress database (May 2007). We studied reference lists and published review articles. Selection criteria Studies evaluating tests of maternal serum in women at 14-24 weeks of gestation for Down's syndrome, compared with a reference standard, either chromosomal verification or macroscopic postnatal inspection. Data collection and analysis Data were extracted as test positive/test negative results for Down's and non-Down's pregnancies allowing estimation of detection rates (sensitivity) and false positive rates (1-specificity). We performed quality assessment according to QUADAS criteria. We used hierarchical summary ROC meta-analytical methods to analyse test performance and compare test accuracy. Analysis of studies allowing direct comparison between tests was undertaken. We investigated the impact of maternal age on test performance in subgroup analyses. Main results Fifty-nine studies involving 341,261 pregnancies (including 1,994 with Down's syndrome) were included. Studies were generally high quality, although differential verification was common with invasive testing of only high-risk pregnancies. Seventeen studies made direct comparisons between tests. Fifty-four test combinations were evaluated formed from combinations of 12 different tests and maternal age; alpha-fetoprotein (AFP), unconjugated oestriol (uE3), total human chorionic gonadotrophin (hCG), free beta human chorionic gonadotrophin (βhCG), free alpha human chorionic gonadotrophin (αhCG), Inhibin A, SP2, CA125, troponin, pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PGF) and proform of eosinophil major basic protein (ProMBP). Meta-analysis of 12 best performing or frequently evaluated test combinations showed double and triple tests (involving AFP, uE3, total hCG, free βhCG) significantly outperform individual markers, detecting six to seven out of every 10 Down's syndrome pregnancies at a 5% false positive rate. Tests additionally involving inhibin performed best (eight out of every 10 Down's syndrome pregnancies) but were not shown to be significantly better than standard triple tests in direct comparisons. Significantly lower sensitivity occurred in women over the age of 35 years. Women who miscarried in the over 35 group were more likely to have been offered an invasive test to verify a negative screening results, whereas those under 35 were usually not offered invasive testing for a negative screening result. Pregnancy loss in women under 35 therefore leads to under ascertainment of screening results, potentially missing a proportion of affected pregnancies and affecting the accuracy of the sensitivity. Authors' conclusions Tests involving two or more markers in combination with maternal age are significantly more sensitive than those involving one marker. The value of combining four or more tests or including inhibin have not been proven to show statistically significant improvement. Further study is required to investigate reduced test performance in women aged over 35 and the impact of differential pregnancy loss on study findings

Simulation study of magnetic holes at the Earth's collisionless bow shock

Recent observations by the Cluster and Double Star spacecraft at the Earth's bow shock have revealed localized magnetic field and density holes in the solar wind plasma. These structures are characterized by a local depletion of the magnetic field and the plasma density, and by a strong increase of the plasma temperature inside the magnetic and density cavities. Our objective here is to report results of a hybrid-Vlasov simulations of ion-Larmor-radius sized plasma density cavities with parameters that are representative of the high-beta solar wind plasma at the Earth's bow shock. We observe the asymmetric self-steepening and shock-formation of the cavity, and a strong localized temperature increase (by a factor of 5–7) of the plasma due to reflections and shock surfing of the ions against the collisionless shock. Temperature maxima are correlated with density minima, in agreement with Cluster observations. For oblique incidence of the solar wind, we observe efficient acceleration of ions along the magnetic field lines by the shock drift acceleration process

The development of QUADAS : a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews

BACKGROUND: In the era of evidence based medicine, with systematic reviews as its cornerstone, adequate quality assessment tools should be available. There is currently a lack of a systematically developed and evaluated tool for the assessment of diagnostic accuracy studies. The aim of this project was to combine empirical evidence and expert opinion in a formal consensus method to develop a tool to be used in systematic reviews to assess the quality of primary studies of diagnostic accuracy. METHODS: We conducted a Delphi procedure to develop the quality assessment tool by refining an initial list of items. Members of the Delphi panel were experts in the area of diagnostic research. The results of three previously conducted reviews of the diagnostic literature were used to generate a list of potential items for inclusion in the tool and to provide an evidence base upon which to develop the tool. RESULTS: A total of nine experts in the field of diagnostics took part in the Delphi procedure. The Delphi procedure consisted of four rounds, after which agreement was reached on the items to be included in the tool which we have called QUADAS. The initial list of 28 items was reduced to fourteen items in the final tool. Items included covered patient spectrum, reference standard, disease progression bias, verification bias, review bias, clinical review bias, incorporation bias, test execution, study withdrawals, and indeterminate results. The QUADAS tool is presented together with guidelines for scoring each of the items included in the tool. CONCLUSIONS: This project has produced an evidence based quality assessment tool to be used in systematic reviews of diagnostic accuracy studies. Further work to determine the usability and validity of the tool continue

History-Adjusted Marginal Structural Models to Estimate Time-Varying Effect Modification

Much of epidemiology and clinical medicine is focused on the estimation of treatments or interventions administered over time. In such settings of longitudinal treatment, time-dependent confounding is often an important source of bias. Marginal structural models are a powerful tool for estimating the causal effect of a treatment using observational data, particularly when time-dependent confounding is present. Recent statistical work presented a generalization of marginal structural models, called history-adjusted marginal structural models. Unlike standard marginal structural models, history-adjusted marginal structural models can be used to estimate modification of treatment effects by time-varying covariates. Estimation of time-dependent causal effect modification is frequently of great practical relevance. For example, clinical researchers are often interested in how the prognostic significance of a biomarker for treatment response can change over time. This article provides a practical introduction to the implementation and interpretation of history-adjusted marginal structural models. The method is illustrated using a clinical question drawn from the treatment of HIV infection. Observational cohort data from San Francisco, California, collected between 2000 and 2004, are used to estimate the effect of time until switching antiretroviral therapy regimen among patients receiving a non-suppressive regimen, and how this effect differs depending on CD4 T cell count

Transcriptional down-regulation of ccr5 in a subset of HIV+ controllers and their family members.

HIV +Elite and Viremic controllers (EC/VCs) are able to control virus infection, perhaps because of host genetic determinants. We identified 16% (21 of 131) EC/VCs with CD4 +T cells with resistance specific to R5-tropic HIV, reversed after introduction of ccr5. R5 resistance was not observed in macrophages and depended upon the method of T cell activation. CD4 +T cells of these EC/VCs had lower ccr2 and ccr5 RNA levels, reduced CCR2 and CCR5 cell-surface expression, and decreased levels of secreted chemokines. T cells had no changes in chemokine receptor mRNA half-life but instead had lower levels of active transcription of ccr2 and ccr5, despite having more accessible chromatin by ATAC-seq. Other nearby genes were also down-regulated, over a region of ~500 kb on chromosome 3p21. This same R5 resistance phenotype was observed in family members of an index VC, also associated with ccr2/ccr5 down-regulation, suggesting that the phenotype is heritable

Effector memory differentiation increases detection of replication-competent HIV-l in resting CD4+ T cells from virally suppressed individuals.

Studies have demonstrated that intensive ART alone is not capable of eradicating HIV-1, as the virus rebounds within a few weeks upon treatment interruption. Viral rebound may be induced from several cellular subsets; however, the majority of proviral DNA has been found in antigen experienced resting CD4+ T cells. To achieve a cure for HIV-1, eradication strategies depend upon both understanding mechanisms that drive HIV-1 persistence as well as sensitive assays to measure the frequency of infected cells after therapeutic interventions. Assays such as the quantitative viral outgrowth assay (QVOA) measure HIV-1 persistence during ART by ex vivo activation of resting CD4+ T cells to induce latency reversal; however, recent studies have shown that only a fraction of replication-competent viruses are inducible by primary mitogen stimulation. Previous studies have shown a correlation between the acquisition of effector memory phenotype and HIV-1 latency reversal in quiescent CD4+ T cell subsets that harbor the reservoir. Here, we apply our mechanistic understanding that differentiation into effector memory CD4+ T cells more effectively promotes HIV-1 latency reversal to significantly improve proviral measurements in the QVOA, termed differentiation QVOA (dQVOA), which reveals a significantly higher frequency of the inducible HIV-1 replication-competent reservoir in resting CD4+ T cells