16(th) IHIW: analysis of HLA population data, with updated results for 1996 to 2012 workshop data (AHPD project report).

We present here the results of the Analysis of HLA Population Data (AHPD) project of the 16th International HLA and Immunogenetics Workshop (16IHIW) held in Liverpool in May-June 2012. Thanks to the collaboration of 25 laboratories from 18 different countries, HLA genotypic data for 59 new population samples (either well-defined populations or donor registry samples) were gathered and 55 were analysed statistically following HLA-NET recommendations. The new data included, among others, large sets of well-defined populations from north-east Europe and West Asia, as well as many donor registry data from European countries. The Gene[rate] computer tools were combined to create a Gene[rate] computer pipeline to automatically (i) estimate allele frequencies by an expectation-maximization algorithm accommodating ambiguities, (ii) estimate heterozygosity, (iii) test for Hardy-Weinberg equilibrium (HWE), (iv) test for selective neutrality, (v) generate frequency graphs and summary statistics for each sample at each locus and (vi) plot multidimensional scaling (MDS) analyses comparing the new samples with previous IHIW data. Intrapopulation analyses show that HWE is rarely rejected, while neutrality tests often indicate a significant excess of heterozygotes compared with neutral expectations. The comparison of the 16IHIW AHPD data with data collected during previous workshops (12th-15th) shows that geography is an excellent predictor of HLA genetic differentiations for HLA-A, -B and -DRB1 loci but not for HLA-DQ, whose patterns are probably more influenced by natural selection. In Europe, HLA genetic variation clearly follows a north to south-east axis despite a low level of differentiation between European, North African and West Asian populations. Pacific populations are genetically close to Austronesian-speaking South-East Asian and Taiwanese populations, in agreement with current theories on the peopling of Oceania. Thanks to this project, HLA genetic variation is more clearly defined worldwide and better interpreted in relation to human peopling history and HLA molecular evolution.

Strategies to work with HLA data in human populations for histocompatibility, clinical transplantation, epidemiology and population genetics: HLA-NET methodological recommendations.

HLA-NET (a European COST Action) aims at networking researchers working in bone marrow transplantation, epidemiology and population genetics to improve the molecular characterization of the HLA genetic diversity of human populations, with an expected strong impact on both public health and fundamental research. Such improvements involve finding consensual strategies to characterize human populations and samples and report HLA molecular typings and ambiguities; proposing user-friendly access to databases and computer tools and defining minimal requirements related to ethical aspects. The overall outcome is the provision of population genetic characterizations and comparisons in a standard way by all interested laboratories. This article reports the recommendations of four working groups (WG1-4) of the HLA-NET network at the mid-term of its activities. WG1 (Population definitions and sampling strategies for population genetics' analyses) recommends avoiding outdated racial classifications and population names (e.g. 'Caucasian') and using instead geographic and/or cultural (e.g. linguistic) criteria to describe human populations (e.g. 'pan-European'). A standard 'HLA-NET POPULATION DATA QUESTIONNAIRE' has been finalized and is available for the whole HLA community. WG2 (HLA typing standards for population genetics analyses) recommends retaining maximal information when reporting HLA typing results. Rather than using the National Marrow Donor Program coding system, all ambiguities should be provided by listing all allele pairs required to explain each genotype, according to the formats proposed in 'HLA-NET GUIDELINES FOR REPORTING HLA TYPINGS'. The group also suggests taking into account a preliminary list of alleles defined by polymorphisms outside the peptide-binding sites that may affect population genetic statistics because of significant frequencies. WG3 (Bioinformatic strategies for HLA population data storage and analysis) recommends the use of programs capable of dealing with ambiguous data, such as the 'gene[rate]' computer tools to estimate frequencies, test for Hardy-Weinberg equilibrium and selective neutrality on data containing any number and kind of ambiguities. WG4 (Ethical issues) proposes to adopt thorough general principles for any HLA population study to ensure that it conforms to (inter)national legislation or recommendations/guidelines. All HLA-NET guidelines and tools are available through its website http://hla-net.eu.

Design and implementation of deformation algorithms for computer assisted orthopedic surgery: application to virtual implant database and preliminary results.

In cranio-maxillofacial and in trauma surgery while making osteosynthesis the surgeons want to reposition bone fractures and make fixation using implants and fixations devices. These devices need to be bent during surgery or prior surgery to fit geometrical boundary conditions defined by the individual anatomy of the patient. In clinical routine, surgeons must frequently repeat several times the "bend and try" process until they get the best fitting. This process often requires up to twenty minutes for a single osteosynthesis plate. A realistic deformation algorithm is then a pre-requisite to a computer-aided planning system which aims to help surgeons to optimally pre-bend the implant in respect to an individual patient bone structure. It has been shown that computer assisted planning system for bendable implant improves the results and operation outcome: shorter operation time, more accuracy, less post-operative implant failure, etc. This paper presents our preliminary results on implementing different types of deformation algorithms in the context of computer assisted orthopedic surgery.

A semi-automatic orthopedic implant management tool for Computer Assisted planning, navigation and simulation: from XML implant database to unified implant access interface.

Nowadays, Computer Assisted Orthopedic planning and navigation systems have been recognized as an important tool that helps surgeons. Various systems have been developed so far, but most of them use non-standard formalisms and techniques. As a result there are no standard concepts for implant and tool management or data formats to store information for use in 3D planning and navigation systems. We addressed these limitations and developed a practical and generic solution which brings benefits for surgeons, implant manufacturers and CAS application developers. We developed a virtual implant database containing geometrical as well as calibration information for orthopedic implants and instruments with a focus on Trauma. This database has been successfully tested with various applications in client/server mode. Nevertheless, the implant information is not static because periodically manufacturers revise implants, resulting in the removal of some implants and addition of new ones. To ease the implant management in respect to implant life cycle, we developed an implant management tool which helps end-users to manage their implants. Currently, this tool allows the addition of new implants, modification of existing ones, deletion of obsolete implants, export of a given implant and also creation of backups. Our implant management system has been successfully tested in the laboratory and gave very promising results. It makes it possible to fill the current existing gap between CAS system, implant manufacturers, hospitals and surgeons.

New orthopaedic implant management tool for computer-assisted planning, navigation, and simulation: from implant CAD files to a standardized XML-based implant database.

Computer-Assisted Orthopaedic Surgery (CAOS) has made much progress over the last 10 years. Navigation systems have been recognized as important tools that help surgeons, and various such systems have been developed. A disadvantage of these systems is that they use non-standard formalisms and techniques. As a result, there are no standard concepts for implant and tool management or data formats to store information for use in 3D planning and navigation. We addressed these limitations and developed a practical and generic solution that offers benefits for surgeons, implant manufacturers, and CAS application developers. We developed a virtual implant database containing geometrical as well as calibration information for orthopedic implants and instruments, with a focus on trauma. This database has been successfully tested for various applications in the client/server mode. The implant information is not static, however, because manufacturers periodically revise their implants, resulting in the deletion of some implants and the introduction of new ones. Tracking these continuous changes and keeping CAS systems up to date is a tedious task if done manually. This leads to additional costs for system development, and some errors are inevitably generated due to the huge amount of information that has to be processed. To ease management with respect to implant life cycle, we developed a tool to assist end-users (surgeons, hospitals, CAS system providers, and implant manufacturers) in managing their implants. Our system can be used for pre-operative planning and intra-operative navigation, and also for any surgical simulation involving orthopedic implants. Currently, this tool allows addition of new implants, modification of existing ones, deletion of obsolete implants, export of a given implant, and also creation of backups. Our implant management system has been successfully tested in the laboratory with very promising results. It makes it possible to fill the current gap that exists between the CAS system and implant manufacturers, hospitals, and surgeons.