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Constructive technology assessment (CTA) differs from other technology assessment methods by emphasizing implementation and development of new technologies over a simple assessment of those technologies' potential impact. CTA, which was developed in Denmark and the Netherlands, seeks to moderate the impact of potentially damaging technologies while taking full advantage of beneficial technologies.

TUBB2B codes for one of the isotypes of β-tubulin and dominant negative variants in this gene result in distinctive malformations of cortical development (MCD), including dysgyria, dysmorphic basal ganglia and cerebellar anomalies. We present a novel family with a heterozygous missense variant in TUBB2B and an unusually mild phenotype. First, at 21 3 7 weeks of gestation ultrasonography revealed a fetus with a relatively small head, enlarged lateral ventricles, borderline hypoplastic cerebellum and a thin corpus callosum. The couple opted for pregnancy termination. Exome sequencing on fetal material afterwards identified a heterozygous maternally inherited variant in TUBB2B (NM_178012.4 (TUBB2B):c.530A > T, p.(Asp177Val)), not present in GnomAD and predicted as damaging. The healthy mother had only a language delay in childhood. This inherited TUBB2B variant prompted re-evaluation of the older son of the couple, who presented with a mild delay in motor skills and speech. His MRI revealed mildly enlarged lateral ventricles, a thin corpus callosum, mild cortical dysgyria, and dysmorphic vermis and basal ganglia, a pattern typical of tubulinopathies. This son finally showed the same TUBB2B variant, supporting pathogenicity of the TUBB2B variant. These observations illustrate the wide phenotypic heterogeneity of tubulinopathies, including reduced penetrance and mild expressivity, that require careful evaluation in pre- and postnatal counseling. • TUBB2B variant c.530A > T, p.(Asp177Val) results in a mild tubulinopathy. • Pathogenic variants in TUBB2B can result in a variable phenotypic severity. • Familial TUBB2B variants are rare and can give intrafamilial variable phenotypes. • Fetal imaging is non-specific therefore complicates prenatal counseling. [ABSTRACT FROM AUTHOR]

The increasing pace of gene discovery in the last decade has brought a major change in the way the genetic causes of brain malformations are being diagnosed. Unbiased genomic screening has gained the first place in the diagnostic protocol of a child with congenital (brain) anomalies and the detected variants are matched with the phenotypic presentation afterwards. This process is defined as "reverse phenotyping". Screening of DNA, through copy number variant analysis of microarrays and analysis of exome data on different platforms, obtained from the index patient and both parents has become a routine approach in many centers worldwide. Clinicians are used to multidisciplinary team interaction in patient care and disease management and this explains why the majority of research that has led to the discovery of new genetic disorders nowadays proceeds from clinical observations to genomic analysis and to data exchange facilitated by open access sharing databases. However, the relevance of multidisciplinary team interaction has not been object of systematic research in the field of brain malformations. This review will illustrate some examples of how diagnostically driven questions through multidisciplinary interaction, among clinical and preclinical disciplines, can be successful in the discovery of new genes related to brain malformations. The first example illustrates the setting of interaction among neurologists, geneticists and neuro-radiologists. The second illustrates the importance of interaction among clinical dysmorphologists for pattern recognition of syndromes with multiple congenital anomalies. The third example shows how fruitful it can be to step out of the "clinical comfort zone", and interact with basic scientists in applying emerging technologies to solve the diagnostic puzzles. • The paper reflects the opinion of the authors on the approach to the genetic research in the field of brain malformations. • Expertise from different fields, state-of -the-art technologies and interdisciplinary interaction foster advances. • Coordinated interdisciplinary approach promises to accelerate discoveries and to improve disease management. [ABSTRACT FROM AUTHOR]

Californian and Dutch efforts to produce electric vehicles are explored and compared. Three strategies are put forward that could turn electric vehicles from an elusive legend, a plaything, into a marketable product: technology forcing creating a market of early promises, experiments geared towards niche development and upscaling (strategic niche management), and the creation of new alliances (technological nexus) which bring technology, the market, regulation and many other factors together. These strategies deployed in the Californian and Dutch context are analyzed in detail to explore their relative strengths and weaknesses and to argue in the end that a combined use of all three will increase the chances that the dominant technological system will change. The successful workings of these strategies crucially depend on the coupling of the variation and selection processes, building blocks for any evolutionary theory of technical change. Evolutioinary theory lacks understanding of these coupling processes. Building on recent insights from the sociology of technology, the authors propose a quasi-evolutionary model whic underpins the analysis of suggested strategies. (Reprinted by permission of the publisher.)