KinOath Kinship Archiver Version 1.4

This talk will introduce a new tool for Humanities research, in particular Ethnology, Linguistics, Law, History, but also Genetics and Archiving. This tool is KinOath Kinship Archiver which is an application for collecting and analysing kinship data. It is designed to be flexible and culturally nonspecific, which is important to prevent extraneous concepts being imposed onto the data being recorded. The kinship data can be linked to external resources such as archive data. Graphical representation of the data is a key feature, it produces publishable quality diagrams that can be exported to SVG, PDF and JPG formats. Data can be imported from GEDCOM, CSV and TIP files. Data can be exported into CSV format, with additional formats becoming available as plugins. KinOath provides very flexible data fields for each individual / entity recorded in the kinship data, this is combined with customisable relation types, customisable symbols and customisable kin types. This means, for example, that any number of genders and kinship relations can be defined and represented on a diagram. The most common format, GEDCOM (Family History Department, 1999), can be imported into KinOath. However this GEDCOM format exhibits cultural specificities because it has a predetermined set of kinship types, genders and initiation ceremonies. We know that there is a wider array of kinship types (e.g. suckling relations (Altorki, 1980)) and genders (e.g. the Māhū of Hawaiʻi (Matzner, 2001)). There are also initiation ceremonies beyond the Christian and Jewish ceremonies that are predefined in GEDCOM. However once this data is imported, all the flexibility of KinOath will be available. KinOath has project based diagrams and freeform diagrams. Freeform diagrams are like a quick sketch; while project diagrams each have a database of kinship data which can be shared across multiple diagrams. Project based diagrams also allow kin type string queries, such that individuals to be found based on their relations to others. Individuals in a project diagram can be duplicated and merged, which can be useful, for example, in correcting data, or merging multiple data sets where some individuals overlap. In freeform diagrams kin terms can be defined with kin type strings and shown on the diagram, organised in groups, imported and exported. In the future it will be possible to overlay these kin terms onto project diagrams. In order to perform statistical analysis, the kinship data for each project or freeform diagram can be exported for use in R or SPSS. This combined with queries based on kin types and other search parameters, provides great potential in the analysis of both the kin data and the archive data that has been recorded. The intended users of Kinoath are any researchers that collect data in a context of social relations. Kinship data is often not systematically included in the metadata of archives, however these kin relations provide a context that enriches that archived data. KinOath is in active development and new features are regularly being added. The plugin framework that KinOath shares with Arbil has made it possible for external developers to add features. The various versions and the manual are available at: http://tla.mpi.nl/tools/tlatools/kinoath/ REFERENCES Family History Department of The Church of Jesus Christ of Latterday Saints, 1999, THE GEDCOM STANDARD DRAFT Release 5.5.1 http://www.phpgedview.net/ged551¬5.pdf Matzner, Andrew. 2001. 'O au no keia: voices from Hawaii's Mahu and transgender communities. Bloomington, Indiana: Xlibris. Altorki, Soraya. 1980. MilkKinship in Arab Society: An Unexplored Problem in the Ethnography of Marriage. Ethnology 19(2): 233-24

Clinical and immunogenetic characteristics of European multicase rheumatoid arthritis families

OBJECTIVE—To describe the characteristics of a new set of European families with affected sib pairs (ASP) collected by the European Consortium on Rheumatoid Arthritis Families (ECRAF) to replicate the results of our first genome scan. Potential gradients for disease severity in Europe and concordance within families were studied.
PATIENTS AND METHODS—From 1996 to 1998 European white families with at least two affected siblings were enrolled in the study. Demographic (sex, age at onset), clinical data (rheumatoid factor (RF), disease duration, erosive disease, extra-articular features (EF)), and HLA-DRB1 oligotyping were analysed.
RESULTS—565 patients with rheumatoid arthritis (RA), belonging to 271 families including 319 affected sib pairs (ASP) were collected. Belgium, France, Italy, the Netherlands, Portugal, and Spain contributed 20, 96, 52, 24, 9, and 70 families, respectively. Sex (78% women), age at onset (mean 44 years), and RF positivity (79%) were similar among the countries. Differences were found in disease duration (11-18 years) and in the prevalence of erosive disease (70-93%), nodules (15-44%), subjective Sjögren's syndrome (5-38%), and EF (3-16%) (p<0.05 in all cases). A total of 22% RA sibs were shared epitope (SE) negative, whereas 47% and 30% carried one and two SE alleles respectively. Carriage of SE differed widely among countries (p<0.0001): no SE alleles (6-36%), one allele (43-60%), and two alleles (20-39%). SE encoding alleles were mainly DRB1*04 in the Netherlands and Belgium, whereas SE carriage was less common and evenly distributed between DRB1*01, *04, and *10 in Mediterranean countries. No concordance within families was found either in age/calendar year of onset (intraclass correlation coefficient <0.50) or in clinical and radiological features (κ<0.22).
CONCLUSIONS—The differences in RA characteristics between European countries and within families underline the heterogeneity of the disease. No clear cut gradient of disease severity was seen in Europe.


Clinical and immunogenetic characteristics of European multicase rheumatoid arthritis families

OBJECTIVE: To describe the characteristics of a new set of European families with affected sib pairs (ASP) collected by the European Consortium on Rheumatoid Arthritis Families (ECRAF) to replicate the results of our first genome scan. Potential gradients for disease severity in Europe and concordance within families were studied. PATIENTS AND METHODS: From 1996 to 1998 European white families with at least two affected siblings were enrolled in the study. Demographic (sex, age at onset), clinical data (rheumatoid factor (RF), disease duration, erosive disease, extra-articular features (EF)), and HLA-DRB1 oligotyping were analysed. RESULTS: 565 patients with rheumatoid arthritis (RA), belonging to 271 families including 319 affected sib pairs (ASP) were collected. Belgium, France, Italy, the Netherlands, Portugal, and Spain contributed 20, 96, 52, 24, 9, and 70 families, respectively. Sex (78% women), age at onset (mean 44 years), and RF positivity (79%) were similar among the countries. Differences were found in disease duration (11-18 years) and in the prevalence of erosive disease (70-93%), nodules (15-44%), subjective Sjögren's syndrome (5-38%), and EF (3-16%) (p<0.05 in all cases). A total of 22% RA sibs were shared epitope (SE) negative, whereas 47% and 30% carried one and two SE alleles respectively. Carriage of SE differed widely among countries (p<0.0001): no SE alleles (6-36%), one allele (43-60%), and two alleles (20-39%). SE encoding alleles were mainly DRB1*04 in the Netherlands and Belgium, whereas SE carriage was less common and evenly distributed between DRB1*01, *04, and *10 in Mediterranean countries. No concordance within families was found either in age/calendar year of onset (intraclass correlation coefficient <0.50) or in clinical and radiological features (kappa<0.22). CONCLUSIONS: The differences in RA characteristics between European countries and within families underline the heterogeneity of the disease. No clear cut gradient of disease severity was seen in Europe

European genetic study on rheumatoid arthritis: is there a linkage of the interleukin-1 (IL-1), IL-10 or IL-4 genes to RA?

The genetic predisposition for rheumatoid arthritis (RA) is only partly explained by the HLA locus and most genetic factors involved in the susceptibility (and/or severity) of the disease await further identification. The first European genome scan in RA families provided suggestive evidence for linkage with a region (3.1/3q13) on chromosome 3, but many other potential RA susceptibility genes have yet to be analysed. Aims. To perform a linkage analysis with microsatellite markers located in the vicinity of the interleukin-1 (IL-1) gene superfamily, the IL-10 gene and the IL-4 gene cluster which might be considered putative candidate loci for RA. Methods. 107 Caucasoid European RA sibpairs from 90 nuclear families were genotyped for markers flanking the genes for the IL-1 superfamily, IL-10 and the IL-4 gene cluster. Linkage analysis based on the identity by descent (IBD) in affected siblings was analysed with the program SIBPALNA. Affected sibpairs were stratified according to the identity by state (IBS) for three markers in the HLA region (DRB1 oligotyping, D6S276 and TNFa microsatellites) and to the presence/absence of erosive disease on X-ray examination. Results. Analysis of the whole family set showed an excess of allele sharing for markers of the IL-1 gene cluster (IBD 60%; P = 0.012) but not for IL-10 or IL-4. After stratification, the evidence of linkage to IL-1 was restricted to HLA concordant sibpairs (n = 32; IBD 70%; P = 0.006). Some evidence of linkage to IL-10 was also observed in HLA concordant sibpairs (IBD 66%; P = 0.03) and in sibpairs with erosive disease (n = 61; IBD 62%; P = 0.02). Conclusions. We found suggestive evidence of linkage of RA to the IL-1 locus. The increased linkage to IL-1 and IL-10 in HLA-identical sibs suggests a possible interaction between these cytokines and the HLA loci. Moreover IL-10 could interact with HLA factors in predisposing to erosive disease. These results need to be tested in additional families for consistency and replication

Remote monitoring technologies in Alzheimer's disease:design of the RADAR-AD study

BACKGROUND: Functional decline in Alzheimer's disease (AD) is typically measured using single-time point subjective rating scales, which rely on direct observation or (caregiver) recall. Remote monitoring technologies (RMTs), such as smartphone applications, wearables, and home-based sensors, can change these periodic subjective assessments to more frequent, or even continuous, objective monitoring. The aim of the RADAR-AD study is to assess the accuracy and validity of RMTs in measuring functional decline in a real-world environment across preclinical-to-moderate stages of AD compared to standard clinical rating scales. METHODS: This study includes three tiers. For the main study, we will include participants (n = 220) with preclinical AD, prodromal AD, mild-to-moderate AD, and healthy controls, classified by MMSE and CDR score, from clinical sites equally distributed over 13 European countries. Participants will undergo extensive neuropsychological testing and physical examination. The RMT assessments, performed over an 8-week period, include walk tests, financial management tasks, an augmented reality game, two activity trackers, and two smartphone applications installed on the participants' phone. In the first sub-study, fixed sensors will be installed in the homes of a representative sub-sample of 40 participants. In the second sub-study, 10 participants will stay in a smart home for 1 week. The primary outcome of this study is the difference in functional domain profiles assessed using RMTs between the four study groups. The four participant groups will be compared for each RMT outcome measure separately. Each RMT outcome will be compared to a standard clinical test which measures the same functional or cognitive domain. Finally, multivariate prediction models will be developed. Data collection and privacy are important aspects of the project, which will be managed using the RADAR-base data platform running on specifically designed biomedical research computing infrastructure. RESULTS: First results are expected to be disseminated in 2022. CONCLUSION: Our study is well placed to evaluate the clinical utility of RMT assessments. Leveraging modern-day technology may deliver new and improved methods for accurately monitoring functional decline in all stages of AD. It is greatly anticipated that these methods could lead to objective and real-life functional endpoints with increased sensitivity to pharmacological agent signal detection