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Purpose: Pathogenic variants in GABRB3 have been associated with a spectrum of phenotypes from severe developmental disorders and epileptic encephalopathies to milder epilepsy syndromes and mild intellectual disability (ID). In this study, we analyzed a large cohort of individuals with GABRB3 variants to deepen the phenotypic understanding and investigate genotype–phenotype correlations. Methods: Through an international collaboration, we analyzed electro-clinical data of unpublished individuals with variants in GABRB3, and we reviewed previously published cases. All missense variants were mapped onto the 3-dimensional structure of the GABRB3 subunit, and clinical phenotypes associated with the different key structural domains were investigated. Results: We characterized 71 individuals with GABRB3 variants, including 22 novel subjects, expressing a wide spectrum of phenotypes. Interestingly, phenotypes correlated with structural locations of the variants. Generalized epilepsy, with a median age at onset of 12 months, and mild-to-moderate ID were associated with variants in the extracellular domain. Focal epilepsy with earlier onset (median: age 4 months) and severe ID were associated with variants in both the pore-lining helical transmembrane domain and the extracellular domain. Conclusion: These genotype–phenotype correlations will aid the genetic counseling and treatment of individuals affected by GABRB3-related disorders. Future studies may reveal whether functional differences underlie the phenotypic differences. © 2021 American College of Medical Genetics and Genomics

Background: Surveillance of congenital anomalies is important to identify potential teratogens. Despite known associations between different anomalies, current surveillance methods examine trends within each subgroup separately. We aimed to evaluate whether hierarchical statistical methods that combine information from several subgroups simultaneously would enhance current surveillance methods using data collected by EUROCAT, a European network of population-based congenital anomaly registries. Methods: Ten year trends (2003 to 2012) in 18 EUROCAT registries over 11 countries were analysed for the following groups of anomalies: neural tube defects, congenital heart defects, digestive system and chromosomal anomalies. Hierarchical Poisson regression models that combined related subgroups together according to EUROCAT’s hierarchy of subgroup coding were applied. Results from hierarchical models were compared to those from Poisson models that consider each congenital anomaly separately. Results: Hierarchical models gave similar results as those obtained when considering each anomaly subgroup in a separate analysis. Hierarchical models that included only around three subgroups showed poor convergence and were generally found to be over-parameterised. Larger sets of anomaly subgroups were found to be too heterogeneous to group together in this way. Conclusions: There were no substantial differences between independent analyses of each subgroup and hierarchical models when using the EUROCAT anomaly subgroups. Considering each anomaly separately therefore remains an appropriate method for the detection of potential changes in prevalence by surveillance systems. Hierarchical models do, however, remain an interesting alternative method of analysis when considering the risks of specific exposures in relation to the prevalence of congenital anomalies, which could be investigated in other studies.

OBJECTIVES: There has been much discussion about the relatively high perinatal mortality seen in the Netherlands (Buitendijk 2004, Europeristat 2009), for which congenital anomalies (CA) are known to be one of the four main risk factors. There was no nationwide routine prenatal screening for CA in the Netherlands until 2007. We have analysed data for a 14-year period from the EUROCAT registries to investigate the effect of the introduction of screening for CA on the perinatal mortality rate in the Netherlands and compared the results with those from other European registries. METHODS: We used data from the European Surveillance of Congenital Anomalies (EUROCAT) database covering the period 1998 to 2011. We included registries that had correctly coded the date of death for more than 80% of their cases. Perinatal mortality was defined as: deaths in the first week after birth plus late foetal deaths and stillbirths from 20 weeks' gestation onwards, excluding terminations of pregnancy for foetal anomalies (TOPFA). RESULTS: A total of 84.832 cases of CA were included from 13 European registries covering a total of 3.1million births. In Europe the perinatalmortality associated with CA decreased from an average of 1.35 per 1000 births in the period 1998-2006 to 1.15 per 1000 births in the period 2007-2011. In the northern Netherlands, it dropped from 1.73 per 1000 births in the period 1998-2006 to 1.00 per 1000 births in the period 2007- 2011. In 2011, the perinatal mortality associated with CA in the northern Netherlands was on the same level as the rest of Europe. Our data also showed that, since the introduction of prenatal screening, more parents have chosen to terminate a pregnancy if congenital anomalies are discovered. CONCLUSIONS: Perinatal mortality associated with congenital anomaly (CA) has decreased in the northern Netherlands since 2005. The introduction of prenatal screening in 2007 markedly contributed to this trend: pregnancies involving CA were terminated more often, leading to a decrease in the perinatal mortality rate. By 2011, the perinatal mortality rate associated with CA in the northern Netherlands was equal to that for the rest of Europe.

The book introduces an alternative solution to the current public transport crisis by augmenting existing public transport infrastructure with urban computing technology in order to alter them to INFOSTRUCTURES. The authors argue in essays for the introduction of urban computing technology into public transport and give an overview of state-of-the-art developments in public transport around the globe and digital technology by presenting research done with master students in architecture at University of Technology, Sydney and Bachelor students in digital computation at University Sydney. A total of twenty student projects presented with striking images together with a brief description of the projects give an impression of how ten students in architecture and ten further student in digital computation deal with the nexus of space, urban screens, sensor and mobile phone technology to wrap public transport with a new digital layer.

The research presented in this paper investigates ways of providing better design applications for technologies in the field of Urban Digital Media (UDM). The work takes an emergent approach, evolving a design strategy through the early engagement of stakeholders. The paper discusses research in a design-led creative intersection between media technology, culture and the arts in the built environment. The case study discusses opportunities for the enhancement of a university campus experience, learning culture and community, through the provision of an integrated digital presence within campus architecture and urban spaces. It considers types of information architecture (Manovich, 2001) and designs for use in urban settings to create communication-rich, advanced and interactive designed spaces (Haeusler, 2009a). The presented research investigates how to create a strategy for display technologies and networked communications to transform and augment the constructed reality of the built environment, allowing new formats of media activity.

This research is an investigation into a creative and technical 'pixel' element that may facilitate Urban Digital Media, a field that inhabits the intersection between architecture, information and culture in the arena of technology and building. It asks how contemporary requirements of public space in our everyday life, such as adaptability, new modes of communication and transformative environments that offer flexibility for future needs and uses, can be addressed by a new form of public display, assembled through the use of an advanced pixel, described as an interactive Polymedia Pixel with situated media device protocol. The weakness of many current media facades for building-scale interactive installation environments lies in the dearth of quality creative content and unresponsiveness in terms of potential human factors, richness of locative situation and contextual interaction (Sauer, 2004). Media facades have evolved from simple 2D visual displays to 3D voxel arrays for depicting static and moving images with a spatial depth dimension (Haeusler, 2009). As a subsequent step in this development, the research investigates a display that reacts to the need for empathetic and responsive urban digital media; integrates multiple modalities; smart energy-saving; and collaborative community engagement. The Polymedia Pixel, which is presented in its research and development in this paper, contributes to the evolution of building-scale interactive installation environments. The paper firstly discusses the attributes of the Polymedia Pixel in order to address the above mentioned weaknesses of public displays. In responding to these necessities, the prototype of the developed Polymedia Pixel with its technology is outlined. The Polymedia Pixel reserach aims to address

Future facades will become 3D displays. New developments in display technology, so called voxels, allow revolutionary architectural expressions. Whereas spatial expressions have been largely determined by the physical attributes of the building material, voxel displays will shift these borders. With examples of contemporary projects this title looks at the latest developments of the 3D technology & considers its significance for our understanding of space & architecture.

'Customer experience' is a term that covers a wide range of activities that take place between suppliers and users of products and services. LaSalle and Britton define it as 'a holistic experience which involves a person - as opposed to a customer - as a whole at different levels and in every interaction between such person and a company' (2003). This research considers a key aspect of such an holistic experience: that which is embodied in the product or service under consideration. In the context of increasing mobile technology convergence, the paper considers new approaches that focus on developing the necessary underlying enablers and common interaction flows that are required to deliver a designed experience, taking into account the increasing number of mobile operating systems and service delivery platforms. Ultimately these models move towards allowing users to 'co-create their own unique experiences' (Pralahad and Ramswamy, 2004). The convergence between IT and telecommunications domains presents a unique challenge to product and service designers. Services are increasingly accessible via multiple delivery devices and delivery networks. This trend has been seen most recently in the advent of Internet based services being delivered via mobile phones where 'mobile service delivery and technologies have become the glue between previously secluded 'telecom' and "IT' domains' (Karrberg and Liebenau, 2006). At the same time network operators are trying to tighten their relationship with their customers by offering 'sticky' services aimed at raising the barriers to customer mobility. These two trends lead to a new design challenge: how to design a recognisably consistent and compelling product customer experience that applies over all delivery services, operating systems and networks. Solutions to this problem have to date been either technology led, focussing on integrated delivery platforms, or reliant on rule-based design. Crucial to this analysis is the 'role

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Techniques that enable groups of people to control or influence digital system applications collectively have been greatly facilitated through the emergence of faster and better image processing and sensing technologies. This paper considers design issues that relate to crowd or group based user interfaces. One key difference when comparing group interface design with one-on-one user interfaces, is that a group format raises issues of digital political determinism within the system algorithms. These include the impact of an individual's weighting within the group; problems relating to inclusivity across certain user groups; and communication of appropriate user interaction to a diverse audience. These issues were explored by the authors' research using an anamorphic, anthropomorphic experimental display screen in a public location. An input mechanism was developed employing human facial expression analysis, to deliver emotionally expressive visual feedback.

A Fundamental introduction to a topic of current interest Overview about the varied media facades that exist, their technology and future development More than 30 breathtaking media facades by ag4, Realities United, UN Studio, Urbanscreen, among others The book introduces a canon of media architectural terminology and shows the history of media facades through early examples of embedding media in architecture, like Times Square, New York, and Centre Pompidou, Paris. State of the art developments are presented with approx. 30 international projects of contemporary media architecture separated and classified in 7 different technical categories: projection facades, rear projection facades, window raster animation, display facades, illuminated facades, mechanical facades and voxel facades. Each of these 7 categories gets introduced via explaining the technology and through the means of built examples. In each example project data are presented with a brief description about the project and the used technology. An analysis of the representational characteristics of media façades lead to an introduction of possible forms of media content and completes the book.

Objectives: Birth defects are a major health burden. Primary prevention is at present emerging, i.e. folate supplementation. When it is not possible, as is still the case for most birth defects, research is needed to determine how an optimal provision of prenatal diagnosis and use of services can be achieved. Ultrasound scans in the midtrimester of pregnancy are now a routine part of antenatal care in most European countries. The objective of this study was to evaluate the prenatal diagnosis of congenital anomalies by fetal ultrasonographic examination across Europe. Methods: Data from 20 registries of congenital malformations in 12 European countries were included. The prenatal ultrasound screening programs in the countries ranged from no routine screening to 3 fetal scans offered, including 2 for biometric purposes and 1 for search of congenital anomalies, the anomaly scan. Results: There were 8, 126 cases with congenital anomalies with an overall prenatal detection rate of 44.3%. Termination of pregnancy was performed in 1, 657 cases (21.8%). There was significant variation in the prenatal detection rate between regions with the lowest detection rate in registries of countries without routine fetal screening (Denmark and The Netherlands) and the highest detection rate in registries of countries with at least 1 anomaly scan (France, Germany, Italy, Spain, UK). However, there were large variations among the registries with a high detection rate. There were significant differences in the prenatal detection rate and proportion of induced abortions between isolated anomalies and associated anomalies (chromosomal aberrations, recognized syndromes, and multiple without chromosomal aberrations or recognized syndromes). Conclusions: Prenatal detection rate of congenital anomalies by fetal scan varies significantly between registries of European countries even with the same screening policy. Prenatal detection of congenital anomalies is significantly higher when associated malformations are present. The rate of induced abortions varies between registries of countries even with the same detection rate of congenital anomalies. The variation described may be due to cultural and policy differences.

Jorg Jenatsch, a leading freedom fighter during the Thirty Year's War in Graubunden, Switzerland, was assassinated on carnival 1639. Jenatsch's controversial biography and the unclear circumstances of his death inspired the formation of various legends, novels and films. In 1959, a skeleton discovered in the cathedral of Chur with remains of wealthy baroque clothing was tentatively attributed to Jenatsch. Here, we reassess the skeleton based on a new exhumation. Our multidisciplinary analysis and the head injuries are consistent with reports of the eyewitnesses of the crime, demonstrating that Jenatsch was killed from behind with a semi-sharp implement, supposedly an axe, as well as by a blow with a broad-surfaced object. Moreover, our facial reconstruction closely matches an oil portrait of Jenatsch, and the HIrisPlex system applied to DNA-extracts from the femoral bone reveals brown eye and dark brown hair colour, which coincides well with the portrait, too. Finally, isotope analysis of the femoral bone and a molar support Jenatsch's high social status, luxury diet and a high mobility in the last decade of his life. This multidisciplinary approach thus reinforces personal identification and provides additional insight into the life of this important historic person beyond written resources.

Each year, more than 4500 pregnancies in the European Union are affected by neural tube defects (NTD). Unambiguous evidence of the effectiveness of peri conceptional folic acid in preventing the majority of neural tube defects has been available since 1991. We report on trends in the total prevalence of neural tube defects up to 2002, in the context of a survey in 18 European countries of periconceptional folic acid supplementation (PFAS) policies and their implementation. EUROCAT is a network of population-based registries in Europe collaborating in the epidemiological surveillance of congenital anomalies. Representatives from 18 participating countries provided information about policy, health education campaigns and surveys of PFAS uptake. The yearly total prevalence of neural tube defects including livebirths, stillbirths and terminations of pregnancy was calculated from 1980 to 2002 for 34 registries, with UK and Ireland estimated separately from the rest of Europe. A meta-analysis of changes in NTD total prevalence between 1989-1991 and 2000-2002 according to PFAS policy was undertaken for 24 registries. By 2005, 13 countries had a government recommendation that women planning a pregnancy should take 0.4 mg folic acid supplement daily, accompanied in 7 countries by government-led health education initiatives. In the UK and Ireland, countries with PFAS policy, there was a 30% decline in NTD total prevalence (95% CI 16-42%) but it was difficult to distinguish this from the pre-existing strong decline. In other European countries with PFAS policy, there was virtually no decline in NTD total prevalence whether a policy was in place by 1999 (2%, 95% CI 28% reduction to 32% increase) or not (8%, 95% CI 26% reduction to 16% increase). The potential for preventing NTDs by periconceptional folic acid supplementation is still far from being fulfilled in Europe. Only a public health policy including folic acid fortification of staple foods is likely to result in large-scale prevention of NTDs. (c) 2005 Elsevier Inc. All rights reserved.

The digital design appears as an integrated process from conceptualization to materialization and fabrication. The main question is: How the new medium changed the workflow in architecture from a linear model to a cyclic model and the role of new materialization as a form of design thinking? This paper is part of a study that investigates the architectural design process and starts from the premise that we should expand the study of design methods to include other approaches. It considers digital fabrication not as a tool, but as an integrated strategy in collaborative digital processes that can allow a better communication along the design process. It presents the development of design methodologies in order to contribute to a greater understanding of the methodology for design projects with caution to the fact that each one reflects the period in which it was developed. info:eu-repo/semantics/publishedVersion