Non-invasive fetal genotyping for maternal alleles with droplet digital PCR: A comparative study of analytical approaches

Objectives

To develop a flexible droplet digital PCR (ddPCR) workflow to perform non-invasive prenatal diagnosis via relative mutation dosage (RMD) for maternal pathogenic variants with a range of inheritance patterns, and to compare the accuracy of multiple analytical approaches.

Methods

Cell free DNA (cfDNA) was tested from 124 archived maternal plasma samples: 88 cases for sickle cell disease and 36 for rare Mendelian conditions. Three analytical methods were compared: sequential probability ratio testing (SPRT), Bayesian and z-score analyses.

Results

The SPRT, Bayesian and z-score analyses performed similarly well with correct prediction rates of 96%, 97% and 98%, respectively. However, there were high rates of inconclusive results for each cohort, particularly for z-score analysis which was 31% overall. Two samples were incorrectly classified by all three analytical methods; a false negative result predicted for a fetus affected with sickle cell disease and a false positive result predicting the presence of an X-linked IDS variant in an unaffected fetus.

Conclusions

ddPCR can be applied to RMD for diverse conditions and inheritance patterns, but all methods carry a small risk of erroneous results. Further evaluation is required both to reduce the rate of inconclusive results and explore discordant results in more detail.     

Climate change mitigation policy paradigms—national objectives and alignments

The aim of this paper is to assess how policy goals in relation to the promotion of green growth, energy security, pollution control and greenhouse gas (GHG) emissions reductions have been aligned in policies that have been implemented in selected countries during the last decades as a basis for discussing how a multi objective policy paradigm can contribute to future climate change mitigation. The paper includes country case studies from Brazil, Canada, China, the European Union (EU), India, Japan, Mexico, Nigeria, South Africa, South Korea and the United States covering renewable energy options, industry, transportation, the residential sector and cross-sectoral policies. These countries and regions together contribute more than two thirds of global GHG emissions. The paper finds that policies that are nationally driven and that have multiple objectives, including climate-change mitigation, have been widely applied for decades in both developing countries and industrialised countries. Many of these policies have a long history, and adjustments have taken place based on experience and cost effectiveness concerns. Various energy and climate-change policy goals have worked together in these countries, and in practice a mix of policies reflecting specific priorities and contexts have been pursued. In this way, climate-change mitigation has been aligned with other policy objectives and integrated into broader policy packages, though in many cases specific attention has not been given to the achievement of large GHG emission reductions. Based on these experiences with policy implementation, the paper highlights a number of key coordination and design issues that are pertinent to the successful joint implementation of several energy and climate-change policy goals.     

Evaluation of methylene blue and riboflavin for the photosensitized degradation of ethylene glycol

Degradation rates ranging from 0.22 ± 0.11 to 1.52 ± 0.50 mg/L-h were measured for ethylene glycol in riboflavin solutions exposed to natural sunlight. Significant degradation rates were noted in systems using 6 and 10 mg/L riboflavin at pH values of 4, 7, and 10. No significant degradation was found in systems using methylene blue as the photosensitizing agent. Possible mechanisms for ethylene glycol degradation include a combination hydrogen or electron abstraction by an excited photosensitizer and reaction with singlet oxygen or reaction with superoxide radicals.     

Flooding and the Role of Planning in England and Wales: A Critical Review

In this paper the authors raise some important questions about the extent to which planning is fostering an environment susceptible to flooding. They argue that severe UK flooding incidents in recent years should result in the government re-examining the planning system to ensure relevancy and effectiveness in dealing with such problems in the future. They identify where the current policy and practice weaknesses lie in planning to limit both flood source and flood impact areas and suggest ways in which the government and the profession could take remedial steps to increase local and regional sustainability.