Comprehensive prenatal diagnostics: Exome versus genome sequencing

Objective

This study aimed to assess the diagnostic yield of prenatal genetic testing using trio whole exome sequencing (WES) and trio whole genome sequencing (WGS) in pregnancies with fetal anomalies by comparing the results with conventional chromosomal microarray (CMA) analysis.

Methods

A total of 40 pregnancies with fetal anomalies or increased nuchal translucency (NT ≥ 5 mm) were included between the 12th and 21st week of gestation. Trio WES/WGS and CMA were performed in all cases.

Results

The trio WES/WGS analysis increased the diagnostic yield by 25% in cases with negative CMA results. Furthermore, all six chromosomal aberrations identified by CMA were independently detected by WES/WGS analysis. In total, 16 out of 40 cases obtained a genetic sequence variant, copy number variant, or aneuploidy explaining the phenotype, resulting in an overall WES/WGS diagnostic yield of 40%. WES analysis provided a more reliable identification of mosaic sequence variants than WGS because of its higher sequencing depth.

Conclusions

Prenatal WES/WGS proved to be powerful diagnostic tools for fetal anomalies, surpassing the diagnostic yield of CMA. They have the potential to serve as standalone methods for prenatal diagnosis. The study highlighted the limitations of WGS in accurately detecting mosaic variants, which is particularly relevant when analyzing chorionic villus samples.     

Droplet digital PCR is a cost-effective method for analyzing long cell-free DNA in maternal plasma: Application in preeclampsia

Objective

Long cell-free DNA (cfDNA) can be found in the plasma of pregnant women and cancer patients. We investigated if droplet digital PCR (ddPCR) can analyze such molecules for diagnostic purposes using preeclampsia as a model.

Method

Plasma samples from ten preeclamptic and sixteen normal pregnancies were analyzed. Two ddPCR assays targeting a single-copy gene, VCP, and one ddPCR assay targeting LINE-1 repetitive regions were used to measure the percentages of long cfDNA >533, 1001, and 170 bp, respectively. The LINE-1 assay was developed as guided by in silico PCR analyses to better differentiate preeclamptic and normal pregnancies.

Results

Preeclamptic patients had a significantly lower median percentage of long cfDNA than healthy pregnant controls, as determined by the LINE-1 170 bp assay (28.9% vs. 35.1%, p < 0.0001) and the VCP 533 bp assay (6.6% vs. 8.7%, p = 0.014). The LINE-1 assay provided a better differentiation than the VCP 533 bp assay (area under ROC curves, 0.94 vs. 0.79).

Conclusion

ddPCR is a cost-effective approach for unlocking diagnostic information carried by long cfDNA in plasma and may have applications for the detection of preeclampsia. Further longitudinal studies with larger cohorts are required to assess the clinical utility of this test.     

Use of recycling stations in Borlänge, Sweden--volume weights and attitudes

This paper presents a study of recycling stations in the municipality of Borl?nge, Sweden. The main objectives were to measure volume weights of recyclables, to facilitate future planning of collection intervals and bin/container volume, and to investigate the general attitudes among the public towards waste management in general and recycling stations in particular. Volume weights measured in bins/containers were: paper/newsprint: 297 kg/m3, glass packaging: 297 kg/m3, metal packaging: 81.7 kg/m3, paper packaging: 27.8 kg/m3, plastic packaging: 28.1 kg/m3. The recycling stations have been in use since 1994. Most visitors (90%) arrived by car but said the visit to the recycling station was not the main purpose of the trip. The results from the interviews indicated that the people who use the recycling stations have found ways to incorporate waste sorting into their everyday lives, with the help of information, design of the collection system and environmental concerns.     

Risk Removed? Steps Towards Building Trust in Humanitarian Mine Action

This article examines the role of building trust in Humanitarian Mine Action (HMA). The role of trust following a mine-clearance operation is largely an unexplored region. Drawing on case studies from Angola, Mozambique and Afghanistan, the article explores how trust can be understood in the context of humanitarian initiatives such as landmine clearance, and outlines the challenges associated with building trust among populations with experience of armed conflict. Because trust is difficult to re-establish following a war, the argument presented here suggests that one way in which this can be done is through building relationships at the organisational and interpersonal levels. The analysis reviews specific measures that mine-action agencies have used to build trust, looking at the strengths and weaknesses of different approaches. The analysis concludes by suggesting general guidelines for how mine-action practitioners can facilitate trust, and by outlining some promising avenues for future research.     

A river water quality model integrated with a web-based geographic information system

Scientists often use mathematical models to assess river water quality. However, the application of the models in environmental management and risk assessment is quite limited because of the difficulty of preparing input data and interpreting model output. This paper presents a study that links ArcIMS, a Web-based Geographic Information System (GIS) software to ROUT, a national and regional scale river model which evolved from the US Environmental Protection Agency's Water Use Improvement and Impairment Model, to create a WWW-GIS-based river simulation model called GIS-ROUT. GIS-ROUT is used to predict chemical concentrations in perennially flowing rivers throughout the continental United States that receive discharges from more than 10,000 publicly owned wastewater treatment plants (WWTPs). The WWTP chemical loadings are calculated from per capita per day disposal of product ingredients and the population served by each plant. Each WWTP, containing data on treatment type and influent and effluent flows, is spatially associated with a specific receiving river segment. Based on user defined treatment-type removal rates for a particular chemical, an effluent concentration for each WWTP is calculated and used as input to the river model. Over 360,000 km of rivers are modeled, incorporating dilution and first order loss of the chemical in each river segment. The integration of spatial data, GIS, the WWW, and modeling in GIS-ROUT makes it possible to organize and analyze data spatially, and view results on interactive maps as well as tables and distribution charts. The integration allows scientists and managers in different locations to coordinate and share their estimations for environmental exposure and risk assessments.     

The targeting of rural environmental policies: an assessment of agri‐environmental schemes in the UK

The targeting of environmental policies holds the key to their effectiveness and value for money. In this paper we look specifically at the targeting of the various agri‐environmental schemes likely to be on offer to UK farmers under a reformed Common Agricultural Policy. The manner in which these schemes are targeted—at groups of farmers or areas of land—and the precision with which target groups or target land is identified will be critical in their success or failure. One approach is to target the farming systems thought most environmentally sensitive. This avoids drawing lines on a map and may allow policy makers to channel money into the hands of economically disadvantaged farmers or those vulnerable to policy change. But there is also a need for a more radical and geographically‐targeted approach if problems like soil erosion and aquifer protection—requiring drastic land use shifts within specified areas—are to be tackled effectively. We assess the scope for using existing datasets to identify land that should be targeted under an American‐style Conservation Reserve Programme in the UK.