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Aims: Arthroplasty surgery of the knee and hip is performed in two to three million patients an-nually. Periprosthetic joint infections occur in 4% of these patients. Debridement, antibiot-ics, and implant retention (DAIR) surgery aimed at cleaning the infected prosthesis often fails, subsequently requiring invasive revision of the complete prosthetic reconstruction. Infection-specific imaging may help to guide DAIR. In this study, we evaluated a bacteria -specific hybrid tracer (99mTc-UBI29-41-Cy5) and its ability to visualize the bacterial load on fem-oral implants using clinical -grade image guidance methods. Methods: 99mTc-UBI29-41- Cy5 specificity for Stapylococcus aureus was assessed in vitro using fluorescence confocal imaging. Topical administration was used to highlight the location of S. aureus cul-tured on femoral prostheses using fluorescence imaging and freehand single photon emis-sion CT (fhSPECT) scans. Gamma counting and fhSPECT were used to quantify the bacterial load and monitor cleaning with chlorhexidine. Microbiological culturing helped to relate the imaging findings with the number of (remaining) bacteria. Results: Bacteria could be effectively stained in vitro and on prostheses, irrespective of the presence of biofilm. Infected prostheses revealed bacterial presence on the transition zone between the head and neck, and in the screw hole. Qualitative 2D fluorescence images could be com-plemented with quantitative 3D fhSPECT scans. Despite thorough chlorhexidine treatments, 28% to 44% of the signal remained present in the locations of the infection that were iden-tified using imaging, which included 500 to 2,000 viable bacteria.Conclusion: The hybrid tracer99mTc-UBI29-41-Cy5 allowed effective bacterial staining. Qualitative real -time fluorescence guidance could be effectively combined with nuclear imaging that enables quantitative monitoring of the effectiveness of cleaning strategies.

Antibodies can prevent malaria by neutralizing the infectious Plasmodium falciparum sporozoites (SPZ) before they establish an infection in the liver. Circumsporozoite protein (CSP), the most abundant surface protein of SPZ is the leading candidate for passive (and subunit) immunization approaches against malaria. Comprehensive assessment of the parasite-inhibitory capacity of anti-CSP monoclonal antibodies (mAbs) is an important step in advancing CSP-based immunization strategies. In this study, we employed a quantitative imaging-based motility assay to quantify the effect of anti-CSP mAbs on SPZ motility, both in vitro and in human skin.Our assay provided a quantitative measure of mAb parasite-inhibitory capacity through measurement of the half-maximal motility inhibitory concentration (IC50M) value for anti-CSP mAbs (IC50M 2A10: 24 nM, IC50M 3SP2: 71 nM). We found a sevenfold discrepancy between the IC50M and the binding saturation concentration measured by ELISA, possibly related to the observed shedding of CSP-mAb complexes during SPZ movement. In a subset of SPZ (5%), in vitro motility was unaffected by the presence of 2A10 while 3SP2 was able to completely block movement. In our ex vivo skin explant model, SPZ proved less susceptible to anti-CSP mAbs compared to SPZ in an in vitro environment. By quantitatively assessing motility, we created a valuable tool that can be used for comprehensive assessment of anti-CSP mAb potency. Insight that will help deepen our understanding of anti-CSP mAb potency and guide selection of the most promising anti-CSP mAbs for downstream clinical development.

Developments within the field of image-guided surgery are ever expanding, driven by collective involvement of clinicians, researchers, and industry. While the general conception of the potential of image-guided surgery is to improve surgical outcome, the specific motives and goals that drive can differ between the different expert groups. To establish the current and future role of intra-operative image guidance within the field of image-guided surgery a Delphi consensus survey was conducted during the 2'd European Congress on Image-guided surgery. This multidisciplinary survey included questions on the conceptual potential and clinical value of image-guided surgery and was aimed at defining specific areas of research and development in the field in order to stimulate further advances towards precision surgery. Obtained results based on questionnaires filled in by 56 panel experts (clinicians: N=30, researchers: N=20 and industry: N=6) were discussed during a dedicated expert discussion session during the conference. The outcome of this Delphi consensus is indicative of the potential improvements offered by image-guided surgery and of the need for further research in this emerging-field, that can be enriched by the identification of reliable molecular targets.

In the quest for precision surgery, this thesis introduces several novel detection and navigation modalities for the localization of cancer-related tissues in the operating room. The engineering efforts have focused on image-guided surgery modalities that use the complementary tracer signatures of nuclear and fluorescence radiation. The first part of the thesis covers the use of “GPS-like” navigation concepts to navigate fluorescence cameras during surgery, based on SPECT images of the patient. The second part of the thesis introduces several new imaging modalities such as a hybrid 3D freehand Fluorescence and freehand SPECT imaging and navigation device. Furthermore, to improve the detection of radioactive tracer-emissions during robot-assisted laparoscopic surgery, a tethered DROP-IN gamma probe is introduced. The clinical indications that are used to evaluate the new technologies were all focused on sentinel lymph node procedures in urology (i.e. prostate and penile cancer). Nevertheless, all presented techniques are of such a nature, that they can be applied to different surgical indications, including sentinel lymph node and tumor-receptor-targeted procedures, localization the primary tumor and metastatic spread. This will hopefully contribute towards more precise, less invasive and more effective surgical procedures in the field of oncology.

After two LADM workshops (Delft, March 2017 and Zagreb, April 2018) and three ISO TC211 meetings, where also LADM revision meetings took place (Copenhagen, May 2018, Wuhan, November 2018 and Maribor, June 2019) there is consensus growing towards the new scope of the standard. This new scope is described in this paper, and it is no exaggeration to state that there is a rather spectacular extension of Edition’s I scope. Below a first impression. Some of the existing parts of the current version of LADM are being refined. The goal is that these refinements will add more semantics to LADM, but are also backwards compatible. A good example of such improvements are the Refined Survey Model (as part of the Surveying and Representation Subpackage) and more rigid representations of the various CodeList and the values they hold (adding more structure and using sematic technologies to define meaning of values). The scope of LADM is extended with a valuation and fiscal perspective. This concerns a conceptual data model in a LADM Valuation Package that can be used to construct information systems for immovable property valuation and taxation and offer a data exchange option. Spatial planning/zoning with legal implications is a further extension of the scope. This new LADM package implies integration of spatial planning and land administration environments and thus, re-use of zones from spatial planning as restrictions to land rights is possible. Both extensions have impact on the definition of land administration: land administration is the process of determining, recording and disseminating information about relationships between people and land - informal, customary and formal use and property rights - and about value and use of land. What is more, the Global Land Indicator Initiative (GLII), seeks to derive a list of globally comparable harmonized land indicators, using existing monitoring mechanisms, and data collection methods as a foundation. Hence, the LADM is extended with attributes allowing monitoring, based on those indicators.

Purpose: To assess the feasibility of using freehand Single Photon Emission Computed Tomography (free-handSPECT) for the identification of technetium-99m-hydroxydiphosphonate (Tc-99m-HDP) positive bone lesions and to evaluate the possibility of using these imaging data-sets for augmented- and virtual-reality based navigation approaches.Material and methods: In 20 consecutive patients referred for scintigraphy with Tc-99m-HDP, 21 three-dimensional freehandSPECT-images were generated using a handheld gamma camera. Concordance of the two different data sets was ranked. Furthermore, feasibility of segmenting the hotspot of tracer accumulation for navigation purposes was assessed.Results: In 86% of the cases freehandSPECT images showed good concordance with the corresponding part of the scintigraphic images. In lesions with a signal to background ratio (SBR) > 1.36, freehandSPECT provided an automatically segmented reference point for navigation purposes. In 14% of the cases (average SBR 1.82, range 1.0-3.4) freehandSPECT images showed intermediate concordance due to difficult anatomical area or negative bone scintigraphy and could not be used as navigation targets.Conclusion: In this pilot study, in 86% of the cases freehandSPECT demonstrated good concordance with traditional scintigraphy. A lesion with a SBR of 1.36 or more was suitable for navigation. These high quality freehandSPECT images supported the future exploration navigation strategies, e.g. guided needle biopsies. (C) 2019 Sociedad Espaiiola de Medicina Nuclear e Imagen Molecular. Published by Elsevier Espatia, S.L.U. All rights reserved.

First Edition of the Land Administration Domain Model (LADM) has three packages related to: Parties (people and organisations); Basic Administrative Units, Rights, Responsibilities, and Restrictions (of ownership rights); spatial units (parcels, and the legal space of buildings and utility networks) with a sub package for Surveying and Representation (geometry and topology). The latter sub-package provides the functionality to manage observations and cadastral surveys measurements.Contents of LADM implementations are based on authentic source documents, including the names of the persons having a role (responsibility) in the process of the initial data acquisition and/or in the maintenance process. This concerns legal/administrative data and spatial data based on field surveys and observations – where responsible professionals can be conveyors, registrars, surveyors, grassroot surveyors, citizens themselves (participatory surveying) and paralegals.Some of the existing parts of Edition I of the LADM are proposed to be refined in the context of development of Edition II of the standard. This will allow for the inclusion of better structured meta data – also in support of participatory approaches in cadastral surveying. Richer semantics may require more rigid representations of the various Code Lists and the values they contain (adding more structure and using sematic technologies to define meaning of values).An extended survey and legal models are proposed and presented in this paper. This implies adjustments from field observations to the spatial database and the generation of quality labels.

The wider recognition and use of ISO 19152 LADM Edition I, is mainly documented through the country profiles that have been developed in multiple jurisdictions across the world. Various approaches for developing country profiles have been followed, without acting in accordance with a specific (official or unofficial) roadmap or methodology. This has resulted in an interesting mosaic of country profiles, which at the same time, highlights the need to outline the basic steps that need to be followed in order to develop a country profile. Currently, the revision of the LADM Edition I is ongoing, and the discussion for the development, maintenance and update of the existing and future LADM-based country profiles has been initiated. Therefore, it is considered a good timing to address the experience gained from the developed country profiles and introduce methodological steps for the development of country profiles.This paper reflects on the country profiles that have been developed so far, identifying similarities and discrepancies on the path followed, bearing in mind the scope and objective of the development of those profiles and their level of maturity, also conforming to the land registration system and national jurisdiction. Thus, the paper is separated in three main parts: the first part that introduces the LADM revision and its scope, reflects on the existing country profiles and outlines the components of the proposed methodology. The second part presents an LADM-based country profile for Malaysia, as an example application of the proposed methodology. Finally, the last part is dedicated to the discussion, conclusions and proposals for future steps in the context of LADM revision.

International laws and frameworks such as the 2030 Agenda for Sustainable Development with its defined Sustainable Development Goals (SDGs), together with the Voluntary guidelines on the responsible governance of tenure of land, fisheries and forests in the context of national food security (VGGTs) are key global cornerstones in the protection of women’s land rights and enabler for women to get land rights. Land rights for women is an issue that is linked to broader issues across geographical regions and cultural and religious differences. The SDGs specifically target women’s land and property rights in ending poverty (target 1.4), achieving food security (target 2.3) and ensuring gender equality (target 5a). To achieve these goals and to act according to these global policies, namely, to have equal land rights for women and men, land ownership and land use records need to include both genders. Though, in many countries, such records are non-existent or not up to date or do not show the reality on the ground. As a result, women are often passed over by the government during tenure recordation processes.

The prime purpose of Cadastral data – whether in the form of maps, survey plans or notes, or a digital database is the definitive demarcation of the extent of properties – and can be seen primarily as a decision support facility (“Can a structure be built here?”, “Where can I build a fence?”, “Should I buy this property”?). There are, however many additional uses for which this information has been applied – such as a base for the recording of assets such as light poles, underground cables, etc. and as a history of the pattern of land use and subdivision. Although secondary, these uses are important, and should be adequately supported.

INTERLIS is an object relational modelling language and a Swiss national standard used to model and exchange cadastre data in a system neutral form. While INTERLIS was invented in Switzerland 30 years ago and used for over 25 years, in recent years the language has been applied also in many international projects founded by the Swiss government (ie. Azerbaijan, Belarus, Colombia, Georgia, Kosovo, etc.). One notable international development is the description of ISO 19152 LADM in the INTERLIS language, therefore enabling the use of all INTERLIS compatible tools (ie. UML/INTERLIS-Editor, compiler, data validation tools, data translation and schema generation) for LADM. The current version 2.4 of INTERLIS already supports geometric data types in 3D space (i.e. point, polyline, polygon). But for some future applications (i.e. 3D cadastres or BIM) some real 3D primitives (i.e. 3D volumetric type) and 3D constraints are still missing. Further, also topological structures for 2D and 3D space partitions are being investigated. For this reason it is planned to release a draft standard version of INTERLIS 3 which includes all missing types and functions by the end of 2018. INTERLIS 3 will also be proposed as an international standard. This paper describes the new features of the INTERLIS 3 language and how those new features can be applied to 3D cadastres, BIM and Smart Cities to solve real world problems.

Managing properties and people’s interests in complex multi-level developments is rapidly increasing the last decade and as a result, current cadastral information systems are facing a growing demand to capture, register, maintain, visualise and disseminate 3D spatial information. This has led to a continuous research, at the international scenery, for 3D models and standardization initiatives that help communicate the legal and spatial notions of the built environment.Each of Australia’s states has already established a well-functioning Cadastral Information System, which are progressively moving towards 3D Cadastre. Alongside, the LADM ISO 19152 has gained ground and since its adoption as international standard there have been several attempts by different jurisdictions worldwide to adopt LADM. This however, does not apply for Australia, as only one country profile has been developed – for Queensland – back in 2012.Considering that the LADM edition I revision has already started and through this process improvement and extensions of the current conceptual model, technical LADM specifications through application schemas and encodings, as well as process models will be discussed and investigated, it was a challenge to investigate the possibilities of adopting LADM in Victoria.Given this background, at this paper an approach to model the spatial counterpart of a future LADM-based profile for Victoria is presented, in the context of exploring the implementation issues of 3D Cadastre in Victoria, Australia using LADM. The current status of 2D and 3D cadastral developments in Victoria is presented and the direction towards the adoption of LADM in Victoria is introduced.To be able to develop a LADM Victoria country profile, which will describe the existing situation, but at the same time will be future proof, as first step the mapping between the two existing data models and LADM classes is performed.

Dense urbanisation has led to an increasing demand and pressure for land development, resulting in the partition of 3D space into different owners sharing delimited property interests on, above or below the land surface. Consequently, cadastral spatial units range from simple, but most common, 2D, to complex 3D collections of spaces worldwide, that are more difficult to handle in terms of surveying, storing in a database, maintaining, visualising, etc. Subsequently, this asks for the categorization and organization of the different types of spatial units that are physically identified and legally recognised in various jurisdictions worldwide. In the context of the Land Administration Domain Model (LADM) (ISO 19152, 2012), the “level” concept (LA_Level class) provides a framework for organising the different types of spatial units. Based on that, five levels of encoding are defined in ISO19152, providing a framework of categorisation of 2D spatial units, represented by five spatial profiles included in Annex E of ISO 19152.Six years after the publication of the first edition of LADM as ISO standard, a lot of research has been carried out by experts from all over the world, and today, the ground seems to be mature for the LADM (edition I) revision, which started in May 2018, as a joint activity with many stakeholders involved (ISO TC211, OGC, FIG, etc.). One of the goals of the revision, among others, is to improve LADM’s current 3D support. This can be achieved through the design of new 3D spatial profiles for the different types of spatial units that are recognised by cadastral authorities in various jurisdictions. New and different 3D spatial units’ types may be considered for inclusion in the standard.To this end, the aim of this paper is to investigate, examine and review - in the context of LADM revision- the different types of real-world spatial units, as they have initially been organised by Thompson et al (2015). Based on the revised taxonomy, spatial profiles for the spatial units’ categories are introduced and (several) are further explored and designed. Hence, the focus on this paper lies on two levels: the taxonomy and the spatial profiles, while the level of encoding is not included in the scope of this paper. However, the investigation of the technical encodings that will be used for the implementation of the 3D spatial profiles is introduced at the paper as future work, underlying its importance. Within this concept, the scope and ambition of LADM revision are discussed.

This paper presents the development of database for the conceptual model of LADM-IndoorGML. The aim of this work is to investigate all issues that related to generating the database and visualizing the content of the database. Based on the result of the transformation from conceptual model to the technical model that has been proposed by (Alattas et al., 2018), we have selected some classes of the conceptual model of LADM-IndoorGML to create a database in PostgreSQL with the extension of PostGIS. By converting those classes from class diagram to SQL DDL, a database has been generated and stored different type of data. A visualization tool has been used to visualize indoor spaces based on RRRs for the users.

Many countries are extending their cadastral visualization systems in the third dimension. The reason for this stems from the increasing complexity of contemporary cities, the growing 3D approach in other fields (including 3D spatial data acquisition, spatial data processing and visualization), which made 3D cadastre technologically feasible, and the need to overcome the issues of 2D visualization. The visualization of cadastral parcels in 3D is a challenge, since legal boundaries are, in many cases, invisible in the real world; so how can we properly represent something that is not visible to our eyes? This paper results from research that looks into problems of occlusion and ambiguous perception (in terms of position, size and shape) of objects in the context of 3D cadastre visualization. The exploration of specific interaction techniques is essential to overcome these issues.The aim of this paper is to provide ’lessons learned’ resulting from the implementation of a 3D cadastre prototype that was built with the specific goal of trying out several visualization options of 3D cadastral information in a web environment. A usability test was carried out to obtain feedback from different groups of users. Usability is meant in terms of effectiveness and efficiency of the system and users’ satisfaction. The test users were subdivided into groups according to different professional domains and expertise. During the test, the users are asked to perform a series of tasks typical of cadastral systems. Each task is accompanied by a description to give the users some context. Then, each user is asked to answer a questionnaire about his or her experience. The results are used to extract general feedback. The outcome of the usability test is crucial to point out the detected limitations in this early stage of the prototype development. Design changes can then be made according to the feedback of the test users.

Property valuation is a process of estimating value of an immovable property. The legal, geometric, physical and environmental characteristics of the immovable property together with the economic indicators are taken into consideration during this process. Traditional cadastral systems only provide two-dimensional (2D) legal and geometric information about property units. However, today’s complex valuation practices (e.g. computer aided mass appraisal) would benefit significantly from three dimensional (3D) information on not only property units but also their physical counterparts (e.g. buildings, building parts). Moreover, 2D and 3D environmental information is needed for determining environmental conditions about immovable properties to better estimate the values of them.A collaborative research initiative has proposed an international valuation information model that extends the LADM for specifying semantics of valuation registries maintained by public authorities. The current version of the LADM Valuation Information Model, however, does not include detailed specification for the environmental characteristics of immovable properties (e.g. presence of views, level of visibility and distance to amenities) which can be derived with 2D and 3D geospatial analyses by means of various data sources.The purpose of this paper is to examine which geospatial analyses, especially 3D analyses, can be used to provide information about immovable properties including environmental and locational characteristics for property valuation activities. Furthermore, it is investigated that how property valuation can benefit from data sources including semantically rich 3D building, city and cadastral models for deriving environmental and locational characteristics of property units. To achieve these objectives, the data sources and geospatial analyses are initially investigated in the context of property valuation. Then, the paper focuses more on viewshed analysis. By using open topography, building and height datasets of the Netherlands and 3D GIS analysis, a viewshed analysis is presented to show how it can be utilized using different data sources for better understanding and explanation of values of the properties. The paper is concluded with a discussion to what extent it is possible and meaningful to include (derived) environmental characteristics of properties in the LADM Valuation Information Model.

Utilities, buildings and infrastructure digital representations are very important set of spatial data for quality and sustainable spatial management and development of community in general. Many countries are on the way of the establishment of the 3D cadastre. Existing 2D cadastral systems are able to make gradual transition to 3D cadastre, but for the implementation of real 3D cadastre in many countries it is necessary to change the regulations. A topographic sign or topographic symbol is representation of a topographicobject on map. In combination with other geodetic and cartographic products we can get to very useful information, often quite relevant in order to provide reference context for a 3D cadastre. Topographic signs on topographic maps and on other geodetic products give a representation of complex real-world situations that are not usually drawn in the cadastral maps. The real world, physical, objects as included on topographic maps, prove the context/reference for the legal spaces. This is true for both the 2D, but perhaps even more for the 3D case. Performing an overlay, if needed after proper orientation, it is easy to combine geodetic and cartographic products in today’s digital environment. Special attention is needed for the tunnels, overpasses, underpasses, bridges and other objects to be registered in 3D cadastrebecause their 2D cadastral description does not meet the needs of modern society. In case of 3D topographic data (e.g. 3D CityGML model), then it would also well possible to implement this into 3D cadastre and combine 3D legal spaces with the 3D real world items from the 3D topographical model. However, this combination/integration is usually not feasible with the cadastral plans (survey plans, field sketches) as those are not draws to scale (in both 2D and3D).

Powered by WebGL, some renderers have recently become available for the visualization of point cloud data over the web, for example Plasio or Potree. We have extended Potree to be able to visualize massive point clouds and we have successfully used it with the second national Lidar survey of the Netherlands, AHN2, with 640 billion points. In addition to the visualization, the publicly available service at http://ahn2.pointclouds.nl/ also features a multi-resolution download tool, a geographic name search bar, a measurement toolkit, a 2D orientation map with field of view depiction, a demo mode and the tuning of the visualization parameters. Potree relies on reorganizing the point cloud data into an multi-resolution octree data structure. However, this reorganization is very time consuming for massive data sets. Hence, we have used a divide and conquer approach to decrease the octree creation time. To achieve such performance improvement we divided the entire space into smaller cells, generated an octree for each of them in a distributed manner and then we merged them into a single massive octree. The merging is possible because the extent of all the nodes of the octrees is known and fixed. All the developed tools are free and open-source (FOSS) and they can be used to visualize over the web other massive point clouds.

Object. To determine the level of mainstream education in a nationwide cohort of adolescents with Down Syndrome (DS), and to find characteristics related to mainstream or special school attendance. Method. Dutch children with DS born in 1992, 1993 or 1994, were assessed when 16–19 years old. Parents scored school enrolment between the age of 4–18 years, general characteristics and the levels of intellectual disability using the Dutch Social Competence Rating Scale. Associations between disability and years in mainstream school were assessed by ordinal logistic regression, adjusting for sex and parental education. Results. We collected data from 170 boys and 152 girls (response 63%); mean age 18.3 years (ranges 16.8–19.9). Intellectual disability was mostly moderate (43%). Most children (74%) entered mainstream education between 4 and 6 years of age. At 13 years 17% was in mainstream school and 7% stayed in up to 16 years. From the age of 8 years onwards the majority was in special education, while 6% never attended school. Girls were more often in mainstream school and stayed in longer. Level of disability was significantly associated with number of years in mainstream education. Conclusion. Three out of four Dutch children with DS entered mainstream primary education, however late entry and high dropout are common.

Background. Undescended testis (UDT) or cryptorchidism is the most common genital anomaly seen in boys and can be treated surgically by orchidopexy. The age at which orchidopexy should be performed is controversial for both congenital and acquired UDT. Methods. A decision analysis is performed in which all available knowledge is combined to assess the outcomes of orchidopexy at different ages. Results. Without surgery, unilateral congenital UDT and bilateral congenital UDT are associated with average losses in quality-adjusted life-years (QALYs) of 1.53 QALYs (3% discounting 0.66 QALYs) and 5.23 QALYs (1.91 QALYs), respectively. Surgery reduces this QALY loss to on average 0.84 QALYs (0.21 QALYs) for unilateral UDT and 1.66 QALYs (0.40 QALYs) for bilateral UDT. Surgery at detection will lead to the lowest QALY loss of 0.91 (0.34) and 1.73 (0.60) QALYs, respectively, for unilateral and bilateral acquired UDT compared with surgery during puberty and no surgery. No sensitivity analysis is able to change the preferences for these strategies. Conclusions. Based on our decision analytic model using societal valuations of health outcomes, surgery for unilateral UDT (both congenital and acquired) yielded the lowest loss in QALYs. Given the modest differences in outcomes, there is room for patient (or parent) preference with respect to the performance and timing of surgery in case of unilateral UDT. For bilateral UDT (both congenital and acquired), orchidopexy at any age provides considerable benefit, in particular through improved fertility. As there is no strong effect of timing, the age at which orchidopexy is performed should be discussed with the parents and the patient. More clinical evidence on issues related to timing may in the future modify these results and hence this advice.

Survival of children with Down syndrome (DS) has improved considerably, but insight into their level of daily functioning upon entering adulthood is lacking. We collected cross-sectional data from a Dutch nationwide cohort of 322 DS adolescents aged 16-19 (response 62.8%) to assess the degree to which they master various practical and social skills, using the Dutch Social competence rating scale and the Children's Social Behavior Questionnaire. Up to 60% mastered some of the skills required for independent functioning, such as maintaining adequate standards of personal hygiene and preparing breakfast. Less than 10% had achieved basic skills such as basic cooking and paying in a shop. It is difficult for DS people to master all the skills necessary to live independently. Ninety percent of adolescents with DS experience significant problems in social functioning.

OBJECTIVE: This study aims to evaluate trends in prevalence of Down syndrome (DS) births in the Netherlands over an 11-year period and how they have been affected by maternal age and introduction of prenatal screening.METHOD: Nationwide data of an 11-year birth cohort (1997-2007) from the Netherlands Perinatal Registry were analyzed. First-trimester combined screening was introduced in 2002, free of charge only for women 36 years of age or older and only on patients' request. Changes in maternal age, prevalence of DS births, and rates of births at

Background and aims Becoming independent is for young people with Down syndrome (DS) not a standard development, because of their intellectual impairment. Parents often wonder what level their child with DS might reach. This study aims to measure the level of self-sufficiency and problem behaviour in a large population based sample of 16–19-year-old people with DS. Methods Parents of Dutch children with DS born in 1992, 1993 and 1994 were invited to participate (n=513). Data were collected by a written questionnaire for the parents, containing the Dutch SRZ (measuring social independence), the Child Behaviour Checklist, the Children’s Social Behaviour Questionnaire, and additional questions on skills and background. Differences between mean values were evaluated using t-tests. Results Mean age of the 322 participating young people with DS was 18.3 years (52.8% boys). Considering their basic daily skills, they reached a level of around 70% of independent functioning. Girls had a higher level of functioning than boys (p

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This paper presents the development of the first geographical information system (GIS) that may be used to manipulate a single dataset at a very large range of scales (different detail levels). The design of this multi-scale GIS is fully integrated in the open DBMS Postgres and the open GIS GEO++. Besides the system design, this paper also gives details of the implementation in the Postgres DBMS environment of three generalization tools: 1. the BLG-tree for line and area simplification, 2. the Reactive-tree for selection based on importance and location, and 3. the GAP-tree for solving problems when using the other two structures for an area partitioning. -from Authors

This paper presents the first fully dynamic and reactive data structure. Reactive data structures are vector based structures tailored to the efficient storage and retrieval of geometric objects at different levels of detail. Geometric selections can be interleaved by insertions of new objects and by deletions of existing objects. The core of the reactive data structure is the Reactive-tree, a geometric index structure, that also takes care of the selection-part of the generalization. Other aspects of the generalization process are supported by introducing associated structures, e.g. the Binary Line Generalization-tree for simplification. -from Author

Persistent objects are objects whose contents may outlive the execution time of the program. This paper describes the process of introducing persistent objects in the object-oriented programming language Procol. The strength of persistent objects in an object-oriented programming language is the integration of a database system with programming language. Persistent objects make the program development easier, because the programmer does not have to implement the explicit loading and saving of data. Besides the general functional aspects, special attention is paid to graphical applications in order to deal with their specific geometric requirements. For example, it must be possible to find, in an efficient manner, all graphical objects that fall within a given region. These issues, persistent objects and their geometric rquirements, have not yet got the attention they deserve in the literature covering object-oriented graphical systems where modeling and functional aspects dominate.

During chemotherapy with a cisplatin-containing combination of drugs, 217 blood samples from 30 cancer patients were analyzed for the presence of the main cisplatin-DNA adduct cis-Pt(NH3)2d(pGpG) (Pt-GG). Cisplatin was administered during 3-h infusions on each of 5 consecutive days, resulting in increasing adduct levels which, on the average, were about twice as high after the fifth as after the first infusion. Higher levels were found in blood samples of patients who received the same total amount of cisplatin in one single 3-h infusion. No significant differences in adduct levels were found during first and repeated courses. The nonlinear dependence of adduct levels on total dose can be attributed to removal of adducts. At 21 h after a very first cisplatin infusion 76% of the adducts were removed. Lower percentages of removal were observed over the 21-h periods following the fourth and fifth infusions of 5-day courses (49 and 53%, respectively). After the initial 21 h the removal of adducts continued, albeit at a slower rate. Substantial interindividual variation was found in the adduct levels, which did correlate with the levels obtained after in vitro cisplatin treatment of blood samples from the same patients but not with their age or gender. Testicular cancer patients with complete tumor response showed higher adduct levels in their blood than those with partial response or progressive disease. When blood samples from 8 healthy volunteers were treated with cisplatin in vitro, the person-to-person variation in adduct levels and the intraindividual variation observed over a 2-year period were found to be in the same range, which was narrower than that observed with samples from treated patients. In vitro studies with human blood showed that the formation of the Pt-GG adduct is proportional to cisplatin concentration and complete after about 1 hour. In some of the in vivo and in vitro cisplatin-treated blood samples, all 4 known platinum-DNA adducts were determined. In all cases Pt-GG was by far the major adduct, and no significant differences were observed with respect to the relative amounts of the 4 adducts. Similar adduct ratios were found in DNA from a testicular tumor obtained from a patient who underwent orchidectomy; the Pt-GG adduct level was about 10-fold higher than that in his blood cells.