The clinical implementation of non-invasive prenatal diagnosis for single-gene disorders: challenges and progress made

Recently, we have witnessed the rapid translation into clinical practice of non-invasive prenatal testing for the common aneuploidies, most notably within the United States and China. This represents a lucrative market with testing being driven by companies developing and offering their services. These tests are currently aimed at women with high/medium-risk pregnancies identified by serum screening and/or ultrasound scanning. Uptake has been impressive, albeit limited to the commercial sector. However, non-invasive prenatal diagnosis (NIPD) for single-gene disorders has attracted less interest, no doubt because this represents a much smaller market opportunity and in the majority of cases has to be provided on a bespoke, patient or disease-specific basis. The methods and workflows are labour-intensive and not readily scalable. Nonetheless, there exists a significant need for NIPD of single-gene disorders, and the continuing advances in technology and data analysis should facilitate the expansion of the NIPD test repertoire. Here, we review the progress that has been made to date, the different methods and platform technologies, the technical challenges, and assess how new developments may be applied to extend testing to a wider range of genetic disorders. © 2013 John Wiley & Sons, Ltd.     

Mitigation of CO<Subscript>2</Subscript> emissions from the road passenger transport sector in Bahrain

There is much optimism that the 2015 Conference of the Parties of the United Nations Framework Convention will yield an agreement on mitigation of climate change, to become effective in 2020. In this context, Bahrain represents a developing country with insufficient data to assess mitigation opportunities: its per capita carbon emissions rank among the world’s highest, yet there has been no research on the reduction potential of its rapidly growing transport sector. We examine this reduction potential and the costs of various mitigation measures and, further, explore barriers and the view of policymakers and experts. Potential benefits of combined mitigation scenarios are also identified based on their acceptability. We adopt a modified participatory method to develop the scenarios, using the long-range energy alternative planning (LEAP) modelling system, and find that an integrated policy approach can deliver a 23 % reduction in carbon dioxide emissions, costing 108 United States dollars per avoided metric tonne, with politically acceptable scenarios. Better performance, however, would require less acceptable approaches. These findings are significant for decision-making in Bahrain and other Gulf Cooperation Council countries; national target preparation and the setting of fuel economy standards should be begun promptly. We offer lessons to other developing countries on the timely regulation of technical specifications and numbers of passenger vehicles. Participatory approaches to the assessment of mitigation measures can advance environmentally effective, economically feasible and politically acceptable scenarios. The global community can use these results to provide necessary technical and financial assistance to developing countries.     

Climate treaties and approaching catastrophes

If the threshold that triggers climate catastrophe is known with certainty, and the benefits of avoiding catastrophe are high relative to the costs, treaties can easily coordinate countries' behavior so as to avoid the threshold. Where the net benefits of avoiding catastrophe are lower, treaties typically fail to help countries cooperate to avoid catastrophe, sustaining only modest cuts in emissions. These results are unaffected by uncertainty about the impact of catastrophe. By contrast, uncertainty about the catastrophic threshold normally causes coordination to collapse. Whether the probability density function has “thin” or “fat” tails makes little difference.     

Dealing with heterogeneous regression slopes in analysis of covariance: new methodology applied to environmental effects monitoring fish survey data

Analysis of covariance (ANCOVA) is a powerful statistical method which incorporates one or more covariates into the analysis to reduce error associated with measurement. ANCOVA (modeling response as a function of fish size) is frequently used to analyze environmental effects monitoring (EEM) fish survey data. In approximately 12% of fish survey data sets taken from cycles 1 to 3 of Environment Canada’s EEM database for pulp and paper mills, the standard assumption of parallel regression slopes is not met. For the first three cycles of the EEM program, these data sets were classified as indicating a mill effect, but for the most part were excluded from subsequent analyses aimed at quantifying the effect. We present two different methods for initially dealing with data sets that exhibit heterogeneous slopes so that they can be analyzed using the parallel slope model. The first method identifies data sets where heterogeneous slopes are forced by a few high-influence observations. The second approach identifies data sets where a model with heterogeneous slopes is statistically, but not practically, significant: with a high coefficient of determination for the parallel slope model. These new methodologies are applied to EEM pulp and paper data sets and about 55% of cases with heterogeneous slopes can be described by a parallel slope model. We also discuss a third method that can be used to describe mill effects when regression slopes remain heterogeneous even after applying the above two methods, enabling comparison with a critical effect size. These new methodologies could benefit the EEM program by enabling more data sets to be incorporated into meta-analyses and be used to make more equitable mill monitoring decisions in the future.     

Hydraulic characterization for steam enhanced remediation conducted in fractured rock

To explore the viability of Steam Enhanced Remediation (SER) in fractured rock a small-scale steam injection and water/vapour extraction pilot study was conducted at the former Loring Air Force Base in northern Maine, USA. A detailed well testing program was undertaken to assist in the design of the injection and extraction well array, and to assess the possibility of off-site heat and contaminant migration. A structurally complex limestone having low matrix porosity and a sparse distribution of fractures underlies the study site. To characterize the groundwater and steam flow pathways, single-well slug tests and more than 100 pulse interference tests were conducted. The results of the well testing indicate that the study site is dominated by steeply dipping bedding plane fractures that are interconnected only between some wells in the injection/extraction array. The SER system was designed to take advantage of interconnected fractures located at depth in the eastern end of the site. An array of 29 wells located in an area of 60 by 40 m was used for steam injection and water/vapour extraction. The migration of heat was monitored in several wells using thermistor arrays having a 1.5 m vertical spacing. Temperature measurements obtained during and after the 3 month steam injection period showed that heat migration generally occurred along those fracture features identified by the pulse interference testing. Based on these results, it is concluded that the pulse interference tests were valuable in assisting with the design of the injection/extraction well geometry and in predicting the migration pathways of the hot water associated with the steam injection. The pulse interference test method should also prove useful in support of any other remedial method dependant on the fracture network for delivery of remedial fluid or extraction of contaminants.