Human parvovirus B19 infection and unbalanced translocation in a case of hydrops fetalis

In a case of hydrops fetalis, serological examination showed a recent maternal human parvovirus B19 infection. Amniocentesis revealed a unique unbalanced translocation between chromosomes 3 and 11 of the fetus. The mother proved to have a balanced reciprocal translocation between chromosomes 3 and 11. A grossly macerated hydropic male fetus was delivered with a flat nose and low implanted deformed ears. Histopathological examination revealed nuclear inclusion bodies in fetal erythroid cells, confirming human parvovirus B19 infection. Parvovirus B19 DNA was demonstrated by in situ hybridization in the nuclei of heart muscle cells. Our finding of two different disorders in one case illustrates the importance of a complete evaluation of every case of hydrops fetalis, especially concerning counselling on the outcome of future pregnancies. The human parvovirus B19 infection will not recur due to the acquired immunity of the mother, whereas the balanced reciprocal translocation will endanger future pregnancies.     

Meteorological variability in NO2 and PM10 concentrations in the Netherlands and its relation with EU limit values

The extent of the exceedance of the EU limit values for nitrogen dioxide (NO₂) and particulate matter (PM₁₀) concentrations within the Netherlands is expected to decrease significantly, in the coming years. Whether limit values will actually be exceeded, in the next decade, depends not only on European, national and local policies, but also on the effects of inevitable interannual meteorological fluctuations. An analysis of model calculations and measurements yields variations (1 sigma) in the annual average concentration of about 5% for NO₂ and 9% for PM₁₀, due to meteorological fluctuations. These deviations from long-term average concentrations affect assessments of future levels, set against limit values. For instance, an NO₂ concentration of 39 μg m^?3, estimated for a given year with long-term average meteorology, indicates that it is likely (chance >66%) that the limit value of 40 μg m^?3 will not be exceeded in that particular year. At the same time, the estimation also indicates, for example, that this situation is unlikely (change <33%) to continue for three years in a row. However, with an estimated concentration of 38 μg m^?3, it is likely that the limit value will not be exceeded for three years in a row. The limit value for the daily average PM₁₀ concentration is equivalent to an annual average of about 32 μg m^?3. This threshold is unlikely to be exceeded for three years in a row, when an annual average concentration of 29 μg m^?3 is estimated. Interannual variations in concentrations of NO₂ and PM₁₀ are linked to large-scale meteorological fluctuations. Therefore, similar results can be expected for other European countries.     

Likelihood of meeting the EU limit values for NO2 and PM10 concentrations in the Netherlands

In 2007, the European limit values for annual average nitrogen dioxide (NO₂) concentration and for daily average particulate matter (PM₁₀) concentration were exceeded along motorways and city streets in the Netherlands. While the road length along which the exceedance occurred is uncertain, model calculations show that the NO₂ concentration was likely to have been exceeded (chance >66%) along about 300 km and PM₁₀ concentration along about 75 km. In addition, the limit values were exceeded ‘about as likely as not’ (chance 33–66%) along a total of 1000 km for NO₂ and 1600 km for PM₁₀. PM₁₀ and NO₂ concentrations must be below the limit values everywhere in Europe, ultimately by 2011 and 2015, respectively. Since estimates of future local concentrations have an uncertainty of about 15–20%, no absolute statements can be made whether concentrations will be below the limit values within the specified time. Model calculations accounting for the effects of current and proposed national and European legislation, and using average meteorology for large-scale and local traffic contributions show strong decreases in likely limit value exceedances in the Netherlands. However, limit value exceedances are still possible (chance >33%) along about 350 km for PM₁₀ by 2011, and about 150 km for NO₂, by 2015. These possible exceedances depend not only on the uncertainties and on national and European policies and their effectiveness, but also on contributions by specific additional local measures. The Netherlands Government has proposed a plan, which includes local measures to meet the limit values everywhere, in time. Although not assessed here due to their specific character, such local measures could reduce exceedances. As the effects of local measures and estimates of concentrations are uncertain, continuous monitoring – possibly together with additional measures – will be needed to adhere to the limit values.     

Rapid whole exome sequencing in pregnancies to identify the underlying genetic cause in fetuses with congenital anomalies detected by ultrasound imaging

Objective

The purpose of this study was to explore the diagnostic yield and clinical utility of trio-based rapid whole exome sequencing (rWES) in pregnancies of fetuses with a wide range of congenital anomalies detected by ultrasound imaging.

Methods

In this observational study, we analyzed the first 54 cases referred to our laboratory for prenatal rWES to support clinical decision making, after the sonographic detection of fetal congenital anomalies. The most common identified congenital anomalies were skeletal dysplasia (n = 20), multiple major fetal congenital anomalies (n = 17) and intracerebral structural anomalies (n = 7).

Results

A conclusive diagnosis was identified in 18 of the 54 cases (33%). Pathogenic variants were detected most often in fetuses with skeletal dysplasia (n = 11) followed by fetuses with multiple major fetal congenital anomalies (n = 4) and intracerebral structural anomalies (n = 3). A survey, completed by the physicians for 37 of 54 cases, indicated that the rWES results impacted clinical decision making in 68% of cases.

Conclusions

These results suggest that rWES improves prenatal diagnosis of fetuses with congenital anomalies, and has an important impact on prenatal and peripartum parental and clinical decision making.     

An interactive simulation and visualization tool for flood analysis usable for practitioners

Developing strategies to mitigate or to adapt to the threats of floods is an important topic in the context of climate changes. Many of the world’s cities are endangered due to rising ocean levels and changing precipitation patterns. It is therefore crucial to develop analytical tools that allow us to evaluate the threats of floods and to investigate the influence of mitigation and adaptation measures, such as stronger dikes, adaptive spatial planning, and flood disaster plans. Up until the present, analytical tools have only been accessible to domain experts, as the involved simulation processes are complex and rely on computational and data-intensive models. Outputs of these analytical tools are presented to practitioners (i.e., policy analysts and political decision-makers) on maps or in graphical user interfaces. In practice, this output is only used in limited measure because practitioners often have different information requirements or do not trust the direct outcome. Nonetheless, literature indicates that a closer collaboration between domain experts and practitioners can ensure that the information requirements of practitioners are better aligned with the opportunities and limitations of analytical tools. The objective of our work is to present a step forward in the effort to make analytical tools in flood management accessible for practitioners to support this collaboration between domain experts and practitioners. Our system allows the user to interactively control the simulation process (addition of water sources or influence of rainfall), while a realistic visualization allows the user to mentally map the results onto the real world. We have developed several novel algorithms to present and interact with flood data. We explain the technologies, discuss their necessity alongside test cases, and introduce a user study to analyze the reactions of practitioners to our system. We conclude that, despite the complexity of flood simulation models and the size of the involved data sets, our system is accessible for practitioners of flood management so that they can carry out flood simulations together with domain experts in interactive work sessions. Therefore, this work has the potential to significantly change the decision-making process and may become an important asset in choosing sustainable flood mitigations and adaptation strategies.     

External drift kriging of NOx concentrations with dispersion model output in a reduced air quality monitoring network

In the mid nineteen eighties the Dutch NO_x air quality monitoring network was reduced from 73 to 32 rural and city background stations, leading to higher spatial uncertainties. In this study, several other sources of information are being used to help reduce uncertainties in parameter estimation and spatial mapping. For parameter estimation, we used Bayesian inference. For mapping, we used kriging with external drift (KED) including secondary information from a dispersion model. The methods were applied to atmospheric NO_x concentrations on rural and urban scales. We compared Bayesian estimation with restricted maximum likelihood estimation and KED with universal kriging. As a reference we also included ordinary least squares (OLS). Comparison of several parameter estimation and spatial interpolation methods was done by cross-validation. Bayesian analysis resulted in an error reduction of 10 to 20% as compared to restricted maximum likelihood, whereas KED resulted in an error reduction of 50% as compared to universal kriging. Where observations were sparse, the predictions were substantially improved by inclusion of the dispersion model output and by using available prior information. No major improvement was observed as compared to OLS, the cause presumably being that much good information is contained in the dispersion model output, so that no additional spatial residual random field is required to explain the data. In all, we conclude that reduction in the monitoring network could be compensated by modern geostatistical methods, and that a traditional simple statistical model is of an almost equal quality.

The role of water in the development of The Netherlands— a historical perspective

In this paper an overview is presented of the landscape development of the low-lying parts of The Netherlands. It is shown that water has played an important role in this development. Since prehistoric times, but especially since about 800 AD, man has gradually occupied the low lands along the sea and the main rivers. Through these settlements a chain of actions and reactions of man and his physical environment was set into motion. This chain of events is briefly outlined. It is stated and also illustrated that not only the characteristics of the landscape of the western part of The Netherlands, but also the organization of the Dutch society has been influenced strongly by manÕs need to cope with the omnipresence of water and the threats and opportunities posed by that. It is concluded that the outlined events can only be understood properly if interdisciplinary research takes a more prominent role than it does now.