All-in-one whole exome sequencing strategy with simultaneous copy number variant,single nucleotide variant and absence-of-heterozygosity analysis in fetuses with structural ultrasound anomalies: A 1-year experience

Objective

We performed a 1-year evaluation of a novel strategy of simultaneously analyzing single nucleotide variants (SNVs), copy number variants (CNVs) and copy-number-neutral Absence-of-Heterozygosity from Whole Exome Sequencing (WES) data for prenatal diagnosis of fetuses with ultrasound (US) anomalies and a non-causative QF-PCR result.

Methods

After invasive diagnostics, whole exome parent-offspring trio-sequencing with exome-wide CNV analysis was performed in pregnancies with fetal US anomalies and a non-causative QF-PCR result (WES-CNV). On request, additional SNV-analysis, restricted to (the) requested gene panel(s) only (with the option of whole exome SNV-analysis afterward) was performed simultaneously (WES-CNV/SNV) or as rapid SNV-re-analysis, following a normal CNV analysis.

Results

In total, 415 prenatal samples were included. Following a non-causative QF-PCR result, WES-CNV analysis was initially requested for 74.3% of the chorionic villus (CV) samples and 45% of the amniotic fluid (AF) samples. In case WES-CNV analysis did not reveal a causative aberration, SNV-re-analysis was requested in 41.7% of the CV samples and 17.5% of the AF samples. All initial analyses could be finished within 2 weeks after sampling. For SNV-re-analysis during pregnancy, turn-around-times (TATs) varied between one and 8 days.

Conclusion

We show a highly efficient all-in-one WES-based strategy, with short TATs, and the option of rapid SNV-re-analysis after a normal CNV result.     

Closing remarks: novel approaches to complex societal change and sustainability

This paper summarizes some personal impressions of the 7th conference of the International Complex Systems Society, co-organized with “Future Earth”, held in Stockholm on August 24–26, 2017. The main point is that it is urgent and important to consider the sustainability conundrum as long-term, society-driven one, and to place societal dynamics at the core of how we, as a global society, came to this point, how ongoing dynamics are driving us towards a tipping point, and which role the Information and Communication Technology revolution plays in that process. A much wider involvement of the social sciences is essential. This also requires major changes in our thinking about sustainability—we need to develop an approach in which change is the natural state of affairs and societies attempt to impose stability on the dynamics involved. We need to focus on learning from the past, about the present, but above all for the future. And we need to shift from an entity-focused approach to a relational one, which pays more attention to contexts and networks. Other issues raised by such a shift in our thinking are about the role of science, the adoption of complex systems approaches and a few others that the paper points to.     

Leadership within regional climate change adaptation networks: the case of climate adaptation officers in Northern Hesse,Germany

In the climate adaptation literature, leadership tends to be an understudied factor, although it may be crucial for regional adaptation governance. This article shows how leadership can be usefully conceptualized and operationalized within regional governance networks dealing with climate adaptation. It applies an integrative framework inspired by complexity leadership theory, distinguishing several leadership functions to enhance the adaptive capacity of regional networks. We focus on one specific institutional innovation, appointed climate adaptation officers, who seek to connect science and governance practice, and to mainstream climate adaptation. Our question is twofold: What is the potential of climate adaptation officers to advance the adaptation agenda and to what extent did their establishment and working practice mirror the various leadership functions needed to raise the adaptive capacity of the regional network they operated in? The integrative leadership framework structures the analysis of climate adaptation officers forming part of a government-funded project seeking to enhance adaptation to climate variability in the central German region of Northern Hesse. The data consist of interviews with scientists and regional authority employees and project documentation including an evaluation. We find that climate adaptation officers raised awareness for climate adaptation and helped to shape and implement a number of projects within the overall KLIMZUG programme, highlighting impeding and enabling factors. The process of setting up this institutional innovation involved all forms of leadership functions and is an example of vertical mainstreaming. Its operation involved most clearly enabling and connective leadership functions and is an example of horizontal mainstreaming.     

A thermodynamically based method to quantify true sorption hysteresis

Sorption of organic chemicals to soils and sediments often shows true hysteresis (i.e., nonsingularity of the sorption-desorption isotherm not attributable to known experimental artifacts). Since true sorption hysteresis is fundamentally important to contaminant fate, a way to quantify it is desirable. Previously proposed indices of hysteresis are empirical and usually depend on the isotherm model. True sorption hysteresis to synthetic and natural organic solids has been attributed to irreversible alteration of the solid during the sorption-desorption cycle. Given this mechanism, we propose the Thermodynamic Index of Irreversibility (TII) for quantifying hysteresis in soils where natural organic matter dominates the sorption process. The TII is based on the difference in free energy between the real desorption state and the hypothetical fully reversible state. The index is 0 for completely reversible systems and approaches 1 as the process tends toward complete irreversibility. It does not require any assumptions about the physical properties or molecular composition of the solid, and it does not depend on a specific equilibrium model. A sensitivity analysis of measurement errors provides general recommendations for the setup of sorption-desorption experiments. The TII was applied to sorption of 1,4-dichlorobenzene (DCB) to two high-organic soils, Pahokee peat (PP) and Amherst soil (AS), and a low-rank coal reference material, Beulah-Zap lignite (BZL). Common artificial causes of hysteresis were eliminated. Hysteresis was significant in the peat and the coal. The TII was clearly concentration dependent for both solids; it decreased with concentration for the peat, but increased with concentration for the coal. The TII allows quantification of hysteresis as a function of sorbate-sorbent combination, concentration, time, and other variables.     

Copper ecotoxicology of marine algae: a methodological appraisal

The production of accurate and reliable data on copper ecotoxicology of marine algae depends on the use of trace metal clean techniques during experimentation. We reviewed the methodologies used in the literature on copper ecotoxicology of marine macro- and microalgae, specifically the use of trace metal clean procedures such as the labware used (glassware vs. plasticware), methods of cleaning the labware (acid soaking and ultrapure water rinsing), stock solution preparation (copper source and acidification), and measurement and reporting of dissolved copper concentrations. In terms of taxonomic classification, the most studied algal groups were the Phyla Ochrophyta, Bacillariophyta, Rhodophyta, and Chlorophyta. In terms of methodology, ～50% of the articles did not specify the labware, ～25% used glassware, and ～25% plasticware; ～30% of the studies specified cleaning protocols for labware to remove trace metal impurities; the copper form used to prepare the stock solutions was specified in ～80% of studies but acidification to stabilise the dissolved copper was performed in only ～20%; and the dissolved copper concentration was measured in only ～40% of studies. We discuss the importance of following trace metal clean techniques for the comparison and interpretation of data obtained on copper ecotoxicology in algae.     

Saturated and Unsaturated Water Flow in Inclined Porous Media

This paper considers the two-dimensional saturated and unsaturated flow of water through inclined porous media, namely a waste dump or hill slope. Since the partial differential equation governing this water flow transforms from being parabolic to elliptic as the water flow varies from unsaturated to saturated, an iterative, finite differencing scheme is used to develop a numerical solution. The model can be used to investigate the effects that hill slope angle, depth of soil cover and hilltop width have on water accumulation in the dump and the time required for saturation to occur at different areas in the dump domain. The accuracy and reliability of the computer based solution is tested for two different boundary conditions – (1) no flow on all boundaries (i.e., the internal redistribution of soil moisture to steady state) and (2) a constant rainfall flux on the dump surface. Numerical studies then show the effects of changing the hill slope angle, depth of layer, and dump geometry on the flow characteristics in the dump.     

Assessing impacts on urban greenspace,waterways, and vegetation in urban planning

Parks, waterways, and vegetation enhance the well-being of urbanites and thus warrant consideration in planning and policy-making. It is, however, difficult to assess how land-use change may impact these features and how this in turn may impact well-being. I use a case-study approach to present a framework that combines geospatial and economic valuation techniques to generate indicators of the effects of land-use policies that alter these amenities on community well-being. This framework quantifies the impacts of land-use change on urban environmental amenities in a way that could help communities plan land use so as to maintain well-being as they urbanise.     

A preliminary assessment of the main causative mechanisms of the “island mass” effect of Barbados

Nutrient enrichment of inshore waters is considered the ultimate cause of the island mass effect of Barbados, and other tropicalislands. The present study is an evaluation of the three principal causative mechanisms of enrichment of Barbados coastal waters, i.e. run-off from land, a nutrient exchange between the benthos and overlying waters and internal waves of lunar periodicity. Attempts to link high precipitation to high primary production rates or low salinity with high nutrient levels were unsuccessful. This suggested that land-drainage was not an important factor. Comparisons of nutrient concentrations and C₁₄ fixation rates in waters overlying two contrasting (sand and coral) benthic situations showed trends rather than statistically valid differences in these production variables. A simple calculation of potential nutrient supply versus actual demand showed that internal waves represent a potential source of enrichment. It is suggested that internal waves contribute to the observed high levels of standing crop and production which are characteristic of an island mass effect.