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.     

A systems perspective of managing error recovery and tactical re-planning of operating teams in safety critical domains

Introduction

Research in human error has provided useful tools for designing procedures, training, and intelligent interfaces that trap errors at an early stage. However, this “error prevention” policy may not be entirely successful because human errors will inevitably occur. This requires that the error management process (e.g., detection, diagnosis and correction) must also be supported. Research has focused almost exclusively on error detection; little is known about error recovery, especially in the context of safety critical systems. The aim of this paper is to develop a research framework that integrates error recovery strategies employed by experienced practitioners in handling their own errors.

Method and Results

A control theoretic model of human performance was used to integrate error recovery strategies assembled from reviews of the literature, analyses of near misses from aviation and command & control domains, and observations of abnormal situations training at air traffic control facilities. The method of system dynamics has been used to analyze and compare error recovery strategies in terms of patterns of interaction, system affordances, and types of recovery plans. System dynamics offer a promising basis for studying the nature of error recovery management in the context of team interactions and system characteristics.

Impact on industry

The proposed taxonomy of error recovery strategies can help human factors and safety experts to develop resilient system designs and training solutions for managing human errors in unforeseen situations; it may also help incident investigators to explore why people's actions and assessments were not corrected at the time.     

Leadership and employees’ perceived safety behaviours in a nuclear power plant: A structural equation model

Leadership is considered an essential element in guaranteeing the safe running of organizations. The purpose of the present study is to find out how leader behaviours influence employees’ safety behaviours (perceived safety behaviours) in the nuclear field. In an attempt to answer this question, the authors of this research have considered the way this influence is exercised, taking into consideration some important factors like safety culture and safety climate. To achieve this, the empowerment leadership model, based on a behavioural approach to leadership, was used. The sample was made up of 566 employees from a Spanish nuclear power plant. The results indicated that when safety culture was strong, leader behaviour generated a higher safety climate among the members, which predicted their perceived safety behaviours. Support was found for a structural model linking leadership and safety behaviour to safety culture and safety climate. The implications of these findings for the theory of safety and the way they can be put into practice are outlined.     

Predicting the economic costs and property value losses attributed to sudden oak death damage in California (2010-2020)

Phytophthora ramorum, cause of sudden oak death, is a quarantined, non-native, invasive forest pathogen resulting in substantial mortality in coastal live oak (Quercus agrifolia) and several other related tree species on the Pacific Coast of the United States. We estimate the discounted cost of oak treatment, removal, and replacement on developed land in California communities using simulations of P. ramorum spread and infection risk over the next decade (2010-2020). An estimated 734 thousand oak trees occur on developed land in communities in the analysis area. The simulations predict an expanding sudden oak death (SOD) infestation that will likely encompass most of northwestern California and warrant treatment, removal, and replacement of more than 10 thousand oak trees with discounted cost of $7.5 million. In addition, we estimate the discounted property losses to single family homes of $135 million. Expanding the land base to include developed land outside as well as inside communities doubles the estimates of the number of oak trees killed and the associated costs and losses. The predicted costs and property value losses are substantial, but many of the damages in urban areas (e.g. potential losses from increased fire and safety risks of the dead trees and the loss of ecosystem service values) are not included.     

Determination of atrazine in surface waters by combination of POCIS passive sampling and ELISA detection

Polar organic compound integrative samplers (POCIS) in combination with instrumental techniques such as LC-MS-MS were previously used to monitor environmental pollutants but the performance of alternative immunochemical methods such as ELISA (enzyme-linked immunosorbent assay) has been explored less. In the present study, POCIS technology was applied to surface water sampling in the Czech Republic, and ELISA was used as a detection technique for the herbicide atrazine. In the first study, 28 samples from streams around small municipal waste water treatment plants (WWTPs) were collected using two different devices (POCISpest and POCISpharm) over the course of 21 days. Elevated atrazine concentrations (up to 25 ng per POCIS) were found in samples down-stream of WWTPs. This observation was also confirmed in another two year study (4 sampling periods) investigating 7 river sites around a major city of Brno as well as the inlet and outlet of the city's WWTP. High atrazine levels were systematically determined at the outlet from the WWTPs (120-605 ng per POCIS). A decreasing trend in the atrazine concentrations in rivers around the city of Brno has been observed, with the highest levels observed within the first sampling period in spring 2007 (100-600 ng per POCIS, with an extreme value of 2760 ng per POCIS). Results of the atrazine ELISA were closely correlated with LC-MS/MS, which confirmed good applicability of ELISA as a cost-effective screening tool.     

Infrared differential absorption Lidar (DIAL) measurements of hydrocarbon emissions

We report the application of an infrared (IR) differential absorption Lidar (DIAL) system (also capable of ultra violet measurements) built at the National Physical Laboratory (NPL), UK, to field measurements of total site emissions (controlled and fugitive) from petrochemical and landfill installations. The validation of the IR-DIAL was carried out via a series of controlled field experiments including comparison to GC analysis and tests against controlled methane releases from a test stack, all detailing agreements on the order of ±20%. In volatile organic compound (VOC) measurements at a UK petrochemical site it was found that the American Petroleum Institute's methodology of the time for calculating the emitted flux underestimated by a factor of 2.4. Also, in a similar field trial it was found that scaling traditional point measurements at easily accessible flanges and valves to represent all flanges and valves on a site led to an underestimation by a factor of 6. In addition to petrochemical examples we also report field measurements from a landfill site to demonstrate the advantageous of the DIAL technique for monitoring area emission sources. In this case study it was found that active (still being filled) cells resulted in significantly greater VOC emission rates (30 kg h(-1)) than closed (≤ 10 kg h(-1)).     

House sparrows selectively eject parasitic conspecific eggs and incur very low rejection costs

Most host species of obligate interspecific brood parasites are under strong selection because such parasitism, e.g., that involving evictor nestmates, is highly costly. Egg rejection is one of the most efficient host defences against avian brood parasites. Many hosts have thus evolved egg-recognition ability and rejection behaviour. However, this defensive mechanism has not evolved in most species where only intraspecific brood parasitism occurs, probably because (1) the eggs of conspecific females are very similar in appearance, making egg rejection less likely to emerge, and (2) such parasitism is frequently less costly than interspecific parasitism. Using a captive population of house sparrows (Passer domesticus) with a low breeding density, we here provide new evidence showing that this species actually has a fine capacity to discriminate conspecific eggs and to eject them (44.2% of foreign eggs ejected) while incurring very low rejection costs (4.2% of own eggs ejected). This result contradicts those previously found in high-density house sparrow populations in which very high rejection costs and very high clutch desertion rates were reported, probably as a consequence of intraspecific competition and infanticide provoked by the high breeding density. The house sparrow has only rarely been reported as the host of an interspecific brood parasite, which implies that it is a newly described example of an altricial species in which egg ejection has evolved and is maintained in response to intraspecific brood parasitism.     

Biocatalytic dechlorination of hexachlorocyclohexane by immobilized bio-Pd in a pilot scale fluidized bed reactor

Lindane (??-hexachlorocyclohexane, ??-HCH) is a recalcitrant and toxic organochlorine insecticide. Due to its non-selective production process and widespread use, HCH isomers and their degradation products have been detected frequently in soils and groundwater. An innovative technology using microbial produced Pd(0) nanoparticles, i.e. bio-Pd, was developed to treat groundwater containing a mixture of HCHs and chlorobenzenes. In a first step, the groundwater was de-ironized and most of the chlorobenzenes were removed in a biological trickling filter. The ??g?L^?1 levels of HCHs and chlorobenzenes were removed in a second step by the bio-Pd-based technology. Therefore, a 200-L pilot scale reactor was developed with 100?mg?L^?1 bio-Pd encapsulated in alginate beads. Hydrogen gas was bubbled at the bottom of the reactor and served to charge the bio-Pd catalyst. The reactor influent contained 5.2???g?L^?1 HCHs and 51.1???g?L^?1 chlorobenzenes. During a test period of 10?days, 29% of the HCH isomers and 63% of the chlorobenzenes were removed applying a nominal hydraulic residence time of 4?h. These removal percentages could be increased to 75 and 68% by doubling the nominal hydraulic residence time to 8?h. This study demonstrated that biologically produced nanoparticles of Pd can be applied for the large-scale remediation of groundwater contaminated with HCHs.     

Voltammetric determination of the herbicide Bifenox in drinking and river water using a silver solid amalgam electrode

A new method for the determination of submicromolar and nanomolar concentrations of herbicide Bifenox using differential pulse voltammetry at a mercury meniscus modified silver solid amalgam electrode is described. This new type of working electrode is non-toxic, environmentally friendly, and compatible with principles of green analytical chemistry, and its surface can be easily electrochemically renewed in the case of passivation. The newly developed direct differential pulse voltammetric determination of Bifenox gives limit of determination 6.7·10^?7 and 6.9·10^?7?M in drinking and river water, respectively. Both the selectivity and the sensitivity can be further increased by preliminary separation and preconcentration using solid phase extraction. This combination enables to reach limit of determination 0.9?×?10^?9 and 1.5?×?10^?9?M for drinking and river water, respectively. Because of lower running and investment costs, this electroanalytical method can be used for large scale monitoring of possible water contamination with tested herbicide.