Prenatally diagnosed developmental abnormalities of the central nervous system and genetic syndromes: A practical review

Developmental brain abnormalities are complex and can be difficult to diagnose by prenatal imaging because of the ongoing growth and development of the brain throughout pregnancy and the limitations of ultrasound, often requiring fetal magnetic resonance imaging as an additional tool. As for all major structural congenital anomalies, amniocentesis with chromosomal microarray and a karyotype is the first-line recommended test for the genetic work-up of prenatally diagnosed central nervous system (CNS) abnormalities. Many CNS defects, especially neuronal migration defects affecting the cerebral and cerebellar cortex, are caused by single-gene mutations in a large number of different genes. Early data suggest that prenatal diagnostic exome sequencing for fetal CNS defects will have a high diagnostic yield, but interpretation of sequencing results can be complex. Yet a genetic diagnosis is important for prognosis prediction and recurrence risk counseling. The evaluation and management of such patients is best done in a multidisciplinary team approach. Here, we review general principles of the genetic work-up for fetuses with CNS defects and review categories of genetic causes of prenatally diagnosed CNS phenotypes.     

Gender in integrated water management: an analysis of variation

Gender is an important variable in water use, policy, and intervention. This article explores this variation and its policy implications. Concepts are applied in several case studies to draw generic conclusions. Variation is related to the purpose of water use (consumptive or productive) and to the local, culture-specific patterns of the intra-household organization of consumption for family welfare (which includes domestic water provision) and income-generation (for which water is an input, especially in rural areas). For domestic water use, the intra-household sharing of unpaid domestic responsibilities is a key gender issue. Water for productive use, on the other hand, is embedded in the gendered organization of household economic activity, as elaborated for smallholder-irrigated agriculture. In female-managed and dual farming systems, where a high proportion of farm decision-makers are women, irrigation agencies need to better target their support. In male-managed farming systems, however, the majority of women lack their own farm enterprise in which water is an input. Women's access to land, markets and credits besides access to water, is at stake. To conclude, given the strong variation in water use along gender lines, gender analysis is indispensable for any concrete water policy and intervention.     

Effect of Climatic Changes on the Formation of Siberian Spruce Generations in Subglotsy Tree Stands of the Southern Urals

The correlation between climatic changes and the numbers of trees in the generations of Siberian spruce (Picea obovata Ledeb.) in subgoltsy tree stands of the Southern Urals was analyzed over the past 200 years. The results showed that the most abundant generations appeared in 1809–1816, 1821–1827, 1839–1845, 1850–1867, 1875–1887, 1891–1896, 1900–1904, 1911–1918, 1923–1932, 1944–1952, 1958–1966, and 1975–1995. Their formation proved to be related to the improvement of thermal conditions of the warm season during the five to seven years before and after the emergence of trees and conditions of the cold season in the year of their emergence, as well as to the periods of increased snow depth in late April in the years 27–32 of tree growth.     

Assessment of the Water Balance of European Forests: A Model Study

As part of the UN-ECE Intensive Monitoring Program, data on precipitation, throughfall and soil solution concentrations are measured on a regular basis in approximately 300 forest stands. These data were used to construct element budgets for European forests. To construct such budgets drainage fluxes have to be modeled. In this paper, the research chain from model selection to data derivation and application of the selected model to 245 of the 300 sites is described. To select a suitable hydrological model the Cl^- balance method, two capacity models (a multi and a single layer version) and a Darcy model have been applied to two forest sites. The results indicate that drainage fluxes calculated with the Darcy model are more accurate than fluxes derived with the capacity model, in particular in situations where water availability is limited. The Darcy model was applied to the sites using a mixture of generic data and site data. Despite the use of generic data, the calculated drainage fluxes appear feasible. Median transpiration fluxes were 350 mm and the lowest values are found in northern Europe and highest values are found in central Europe. Median drainage fluxes were 150 mm yr^-1 with the highest values in areas with high rainfall. Uncertainty analyses indicate that the use of local instead of interpolated meteorological data leads to lower drainage fluxes at 70% of the sites. The median deviation in calculated drainage fluxes is 20 mm yr^-1. The use of local soil data had little impact on the calculated fluxes.     

Process‐orientation versus outcome‐orientation during organizational change: the role of organizational identification

In this paper we argue that organizational identification is predictive of employee interests and concerns during periods of organizational change. More specifically, we assert that organizational identification may largely determine whether employees may be focused upon the change related outcomes (e.g., salary, expenses, etc.), or on the change processes (e.g., procedures, voice and participation options, etc.). Data of both a scenario experiment and a survey are presented indicating that high and low identifiers indeed are differentially interested in process and outcome information. The results suggest that people who identify less with the organization are more likely to be focused upon the change outcomes then on the change process, while people who identify highly (i.e., deep structure) with the organization are more likely to be focused upon the change processes then on the change outcomes. The benefits of awareness of organizational members' level of identification for organizational change management are discussed. Copyright © 2006 John Wiley & Sons, Ltd.     

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.