A prospective study on rapid exome sequencing as a diagnostic test for multiple congenital anomalies on fetal ultrasound

Objective

Conventional genetic tests (quantitative fluorescent-PCR [QF-PCR] and single nucleotide polymorphism-array) only diagnose ~40% of fetuses showing ultrasound abnormalities. Rapid exome sequencing (rES) may improve this diagnostic yield, but includes challenges such as uncertainties in fetal phenotyping, variant interpretation, incidental unsolicited findings, and rapid turnaround times. In this study, we implemented rES in prenatal care to increase diagnostic yield.

Methods

We prospectively studied 55 fetuses. Inclusion criteria were: (a) two or more independent major fetal anomalies, (b) hydrops fetalis or bilateral renal cysts alone, or (c) one major fetal anomaly and a first-degree relative with the same anomaly. In addition to conventional genetic tests, we performed trio rES analysis using a custom virtual gene panel of ~3850 Online Mendelian Inheritance in Man (OMIM) genes.

Results

We established a genetic rES-based diagnosis in 8 out of 23 fetuses (35%) without QF-PCR or array abnormalities. Diagnoses included MIRAGE (SAMD9), Zellweger (PEX1), Walker-Warburg (POMGNT1), Noonan (PTNP11), Kabuki (KMT2D), and CHARGE (CHD7) syndrome and two cases of Osteogenesis Imperfecta type 2 (COL1A1). In six cases, rES diagnosis aided perinatal management. The median turnaround time was 14 (range 8-20) days.

Conclusion

Implementing rES as a routine test in the prenatal setting is challenging but technically feasible, with a promising diagnostic yield and significant clinical relevance.     

An agent-based approach to explore the effect of voluntary mechanisms on land use change: A case in rural Queensland,Australia

In rural regions, land use changes (LUC) are often the result of the decision-making of individual farmers. To influence this decision-making, compulsory and voluntary mechanisms are implemented. However, farmers’ decision-making is a heterogeneous process that depends on their ability and willingness to take certain decisions. Discrepancies between farmers’ ability and willingness and the design of voluntary mechanisms occur frequently. This makes it necessary to understand how farmers’ participation in these mechanisms can affect LUC. The aim of this paper was to demonstrate an agent-based approach to analyse and explore how voluntary mechanisms can influence LUC processes in rural regions. This approach was applied to a rural region in Australia, where clearing of native vegetation has occurred for agricultural development. Historical land cover data and semi-structured interviews were used to parameterise an agent-based model. Factors that influence farmers’ ability and willingness to participate in these mechanisms were identified. Three scenarios were simulated with the model to explore how the implementation of different voluntary mechanisms can affect the landscape structure of the region. This paper identifies how the diversity of farmers’ decision-making can influence the landscape structure in the region. The advantages and limitations of an agent-based approach in relation to LUC research and policy are discussed.     

Mainstreaming climate adaptation into urban planning: overcoming barriers, seizing opportunities and evaluating the results in two Dutch case studies

With cities facing climate change, climate adaptation is necessary to reduce risks such as heat stress and flooding and maintain the goals of sustainable urban development. In climate change literature, the focus has been on developing a new dedicated policy domain for climate adaptation. Yet, empirical evidence shows that in practice actors are searching for solutions that not only serve climate adaptation, but integrate the adaptation objective in existing policy domains (e.g., urban planning, water management, public health). The integration of adaptation in other policy domains, also called “mainstreaming climate adaptation,” can stimulate the effectiveness of policy making through combining objectives, increase efficient use of human and financial resources and ensure long-term sustainable investments. A better understanding of the process of mainstreaming is, however, lacking. The article introduces a conceptual model for mainstreaming climate adaptation to enhance our understanding of the concept as well as the barriers and opportunities that influence these integration processes and to explore strategies for overcoming barriers and creating opportunities. Two Dutch case studies—related to urban planning—are used to illustrate the value of the model. The cases demonstrate the dynamic process of mainstreaming and raise discussion of the appropriate criteria for evaluating mainstreaming in relation to the aims of climate adaptation. The paper concludes with an exploration of specific strategies to facilitate the mainstreaming of adaptation in existing and new policy domains.     

Spatial and temporal analysis of vegetation change in agricultural landscapes: A case study of two brigalow (Acacia harpophylla) landscapes in Queensland, Australia

The majority of landscapes around the world have been modified or transformed by human activities to meet the needs of human societies. The loss of native vegetation for agricultural development affects the sustainability of growing proportion of the world's ecosystems. Factors such as land tenure, roads and agricultural intensification, together with biophysical properties, have been cited as drivers of deforestation. This paper combined analysis of the historical drivers of change with analysis of the trends of deforestation since 1945 in two brigalow landscapes (100,000 ha) in sub-tropical Australia. A selection of these drivers were then applied at a property-level (1000 ha) to test their influence on native vegetation retention. Regression trees were used to identify significant human drivers and biophysical properties, and then a generalised linear modelling approach was used to quantify the effect of these factors on the proportion of remnant native vegetation. Results showed that until the mid-20th century, government policies to intensify settlement did not result in increased agricultural production, but since this time, landscape change has been rapid, and has particularly affected ecosystems on fertile clay soils. Although socio-economic factors were critical in driving deforestation, after 60 years of agricultural intensification by far the most significant explanatory variable determining the proportion of native vegetation retained at a property scale was the suitability of the soil for agriculture. Property size was an important secondary influence. The results were not, by and large, consistent with other studies of landscape change and suggest that generalised principles explaining deforestation may be elusive. Solutions to the problem of over-clearance of native vegetation, therefore, need to be tailored to the specific regional situations encountered.     

Methyl chloride emissions from halophyte leaf litter: dependence on temperature and chloride content

Methyl chloride (CH₃Cl) is the most abundant natural chlorine containing compound in the atmosphere, and responsible for a significant fraction of stratospheric ozone destruction. Understanding the global CH₃Cl budget is therefore of great importance. However, the strength of the individual sources and sinks is still uncertain. Leaf litter is a potentially important source of methyl chloride, but factors controlling the emissions are unclear. This study investigated CH₃Cl emissions from leaf litter of twelve halophyte species. The emissions were not due to biological activity, and emission rates varied between halophyte species up to two orders of magnitude. For all species, the CH₃Cl emission rates increased with temperature following the Arrhenius relation. Activation energies were similar for all investigated plant species, indicating that even though emissions vary largely between plant species, their response to changing temperatures is similar. The chloride and methoxyl group contents of the leaf litter samples were determined, but those parameters were not significantly correlated to the CH₃Cl emission rate.     

An enormous Jurassic turtle bone bed from the Turpan Basin of Xinjiang, China

A spectacular new terrestrial Konzentratlagerst?tte is introduced from the Turpan Basin of Xinjiang, China that probably belongs to the late Middle Jurassic Qigu Formation. It contains a mass accumulation of “xinjiangchelyid” turtles preliminarily identified as Annemys sp. In the zone with the highest turtle concentration, complete and articulated turtle skeletons are tightly packed at a density of up to 36 turtles per square meter. The fossiliferous layer is thickened here and shows an erosional base. This high concentration zone outcrops approximately 10?m in length and shows no decrease in turtle density after exposing 2?m of the layer into the hillside. Adjacent is a more expansive zone of at least 10?m by 30?m. In this region, the fossiliferous layer is evenly thick, and approximately five, fully disarticulated turtles are present per square meter. A conservatively estimated 1,800 turtles may, therefore, have been deposited at this site. It is likely that these aquatic turtles gathered in a retreating water hole in a riverine environment during a drought, much as some aquatic turtles will do today, but perished when the habitat dried up completely. A following catastrophic rainfall event caused a debris flow, possibly channelized in a dry river bed, which transported complete turtles, disarticulated turtles, and mudstone clasts and deposited them after a short distance. This taphonomic model is consistent with previous environmental reconstructions of the Turpan Basin during the late Middle Jurassic in predicting the episodic breakdown of regional monsoonal circulation resulting in a seasonally dry climate with severe episodic droughts.