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.     

Effects of flow regimes altered by dams on survival, population declines, and range-wide losses of California river-breeding frogs

Widespread alteration of natural hydrologic patterns by large dams combined with peak demands for power and water delivery during summer months have resulted in frequent aseasonal flow pulses in rivers of western North America. Native species in these ecosystems have evolved with predictable annual flood-drought cycles; thus, their likelihood of persistence may decrease in response to disruption of the seasonal synchrony between stable low-flow conditions and reproduction. We evaluated whether altered flow regimes affected 2 native frogs in California and Oregon (U.S.A.) at 4 spatial and temporal extents. We examined changes in species distribution over approximately 50 years, current population density in 11 regulated and 16 unregulated rivers, temporal trends in abundance among populations occupying rivers with different hydrologic histories, and within-year patterns of survival relative to seasonal hydrology. The foothill yellow-legged frog (Rana boylii), which breeds only in flowing water, is more likely to be absent downstream of large dams than in free-flowing rivers, and breeding populations are on average 5 times smaller in regulated rivers than in unregulated rivers. Time series data (range = 8 - 19 years) from 5 populations of yellow-legged frogs and 2 populations of California red-legged frogs (R. draytonii) across a gradient of natural to highly artificial timing and magnitude of flooding indicate that variability of flows in spring and summer is strongly correlated with high mortality of early life stages and subsequent decreases in densities of adult females. Flow management that better mimics natural flow timing is likely to promote persistence of these species and others with similar phenology.     

Role of winter temperature and climate change on the survival and future range expansion of the hemlock woolly adelgid (Adelges tsugae) in eastern North America

Global climate change has already affected the abundances, range limits, and interactions of many species. The hemlock woolly adelgid (Adelges tsugae), an invasive insect introduced to eastern North America from Japan, has decimated stands of eastern hemlock (Tsuga canadensis) and Carolina hemlock (T. caroliniana) from Georgia to Connecticut. However, its spread across central and northern New England has been slowed substantially by its inability to tolerate cold winter temperatures. Using data from previous lab and field studies collected over the past 17 years, including adelgid spread and overwintering mortality, we first characterize the temperature conditions that may limit adelgid spread. We then show how, in the future, rising winter temperatures due to climate change are likely to remove the conditions currently limiting adelgid spread, and facilitate the northward expansion as more suitable habitat becomes available.     

X-ray microspectroscopy and chemical reactions in soil microsites

Soils provide long-term storage of environmental contaminants, which helps to protect water and air quality and diminishes negative impacts of contaminants on human and ecosystem health. Characterizing solid-phase chemical species in highly complex matrices is essential for developing principles that can be broadly applied to the wide range of notoriously heterogeneous soils occurring at the earth's surface. In the context of historical developments in soil analytical techniques, we describe applications of bulk-sample and spatially resolved synchrotron X-ray absorption spectroscopy (XAS) for characterizing chemical species of contaminants in soils, and for determining the uniqueness of trace-element reactivity in different soil microsites. Spatially resolved X-ray techniques provide opportunities for following chemical changes within soil microsites that serve as highly localized chemical micro- (or nano-)reactors of unique composition. An example of this microreactor concept is shown for micro-X-ray absorption near edge structure analysis of metal sulfide oxidation in a contaminated soil. One research challenge is to use information and principles developed from microscale soil chemistry for predicting macroscale and field-scale behavior of soil contaminants.     

Mangrove vulnerability modelling in parts of Western Niger Delta, Nigeria using satellite images, GIS techniques and Spatial Multi-Criteria Analysis (SMCA)

Mangroves are known for their global environmental and socioeconomic value. Despite their importance, mangrove like other ecosystems is now being threatened by natural and human-induced processes that damage them at alarming rates, thereby diminishing the limited number of existing mangrove vegetation. The development of a spatial vulnerability assessment model that takes into consideration environmental and socioeconomic criteria, in spatial and non-spatial formats has been attempted in this study. According to the model, 11 different input parameters are required in modelling mangrove vulnerability. These parameters and their effects on mangrove vulnerability were selected and weighted by experts in the related fields. Criteria identification and selection were mainly based on effects of environmental and socioeconomic changes associated with mangrove survival. The results obtained revealed the dominance of socioeconomic criteria such as population pressure and deforestation, with high vulnerability index of 0.75. The environmental criteria was broadly dispersed in the study area and represents vulnerability indices ranging from 0.00?C0.75. This category reflects the greater influence of pollutant input from oil wells and pipelines and minimal contribution from climatic factors. This project has integrated spatial management framework for mangrove vulnerability assessment that utilises information technology in conjunction with expert knowledge and multi-criteria analysis to aid planners and policy/ decision makers in the protection of this very fragile ecosystem.     

Operators’ signal-detection performance in video display unit monitoring tasks of the main control room

This study evaluated the operators’ signal-detection performance in video display unit (VDU) monitoring tasks of the main control room (MCR). So far the study of the relationship between VDU design strategy and human errors has been superficial. To validate the effect of VDUs design strategies on operating errors in the MCR, this present research adopted a within subject experimental design to develop different experimental treatments based on two types of display modes included consistent mode and mixed mode. A total of 13 undergraduate and graduate students were recruited as participants in the experiment. Dependent variables included situation awareness, reaction time, error frequency, and subjective performance. Some research support was found for the representation principles. The conclusions of this study could not only be implemented by the human-system interface (HSI) designers of a MCR in the advanced nuclear power plant (NPP) but also could be generalized to the extent that other digital workstation similar to the MCR.     

Database-driven models of the world's Large Marine Ecosystems

We present a new methodology for database-driven ecosystem model generation and apply the methodology to the world's 66 currently defined Large Marine Ecosystems. The method relies on a large number of spatial and temporal databases, including FishBase, SeaLifeBase, as well as several other databases developed notably as part of the Sea Around Us project. The models are formulated using the freely available Ecopath with Ecosim (EwE) modeling approach and software. We tune the models by fitting to available time series data, but recognize that the models represent only a first-generation of database-driven ecosystem models. We use the models to obtain a first estimate of fish biomass in the world's LMEs. The biggest hurdles at present to further model development and validation are insufficient time series trend information, and data on spatial fishing effort.     

Local Perceptions of Changes in Traditional Ecological Knowledge: A Case Study from Malekula Island,Vanuatu

Traditional ecological knowledge (TEK) is a critical global resource that may be eroding amid social and environmental change. Here, we present data on local perceptions of TEK change from three communities on Malekula Island in Vanuatu. Utilizing a structured interview (n = 120), we find a common perception of TEK loss. Participants defined two key periods of TEK erosion (roughly 1940–1960 and 1980–present), and noted that TEK decline was driven both external (e.g., church) and internal (e.g., shifting values) processes. Erosion was perceived to more comprehensive in the worldview domain than in aspects of ethnobiological knowledge and practice. These data indicate the perceived fragility of TEK systems and the complexity of TEK change. TEK systems are critical to natural resource management, and data such as these will assist in designing nuanced responses to the ongoing loss of cultural knowledge and practice.