A novel human leucocyte antigen-DRB1 genotyping method based on multiplex primer extension reactions

We have developed and validated a semi-automated fluorescent method of genotyping human leucocyte antigen (HLA)-DRB1 alleles, HLA-DRB1*01-16, by multiplex primer extension reactions. This method is based on the extension of a primer that anneals immediately adjacent to the single-nucleotide polymorphism with fluorescent dideoxynucleotide triphosphates (minisequencing), followed by analysis on an ABI Prism 3700 capillary electrophoresis instrument. The validity of the method was confirmed by genotyping 261 individuals using both this method and polymerase chain reaction with sequence-specific primer (PCR-SSP) or sequencing and by demonstrating Mendelian inheritance of HLA-DRB1 alleles in families. Our method provides a rapid means of performing high-throughput HLA-DRB1 genotyping using only two PCR reactions followed by four multiplex primer extension reactions and PCR-SSP for some allele groups. In this article, we describe the method and discuss its advantages and limitations.

The effect of transforming growth factor β1 gene polymorphisms in ankylosing spondylitis

Objectives. To determine whether genetic polymorphisms in or near the transforming growth factor β1 (TGFB1) locus were associated d with susceptibility to or severity of ankylosing spondylitis (AS). Methods. Five intragenic single-nucleotide polymorphisms (SNP) and three microsatellite markers flanking the TGFB1 locus were genotyped. Seven hundred and sixty-two individuals from 184 multiplex families were genotyped for the microsatellite markers and two of the promoter SNPs. One thousand and two individuals from 212 English and 170 Finnish families with AS were genotyped for all five intragenic SNPs. A structured questionnaire was used to assess the age of symptom onset, disease duration and disease severity scores, including the BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and BASFI (Bath Ankylosing Spondylitis Functional Index). Results. A weak association was noted between the rare TGFB1 + 1632 T allele and AS in the Finnish population (P = 0.04) and in the combined data set (P = 0.03). No association was noted between any other SNPs or SNP haplotype and AS, even among those families with positive non-parametric linkage scores. The TGFB1 +1632 polymorphism was also associated with a younger age of symptom onset (English population, allele 2 associated with age of onset greater by 4.2 yr, P = 0.05; combined data set, allele 2 associated with age of onset greater by 3.2 yr, P = 0.02). A haplotype of coding region SNPs (TGFB1 +869/ +915+1632 alleles 2/1/2) was associated with age of symptom onset in both the English parent-case trios and the combined data set (English data set, haplotype 2/1/2 associated with age of onset greater by 4.9 yr, P = 0.03; combined data set, haplotype 2/1/2 associated with greater age of onset by 4.2 yr, P = 0.006). Weak linkage with AS susceptibility was noted and the peak LOD score was 1.3 at distance 2 cM centromeric to the TGFB1 gene. No other linkage or association was found between quantitative traits and the markers. Conclusion. This study suggests that the polymorphisms within the TGFB1 gene play at most a small role in AS and that other genes encoded on chromosome 19 are involved in susceptibility to the disease.

Interleukin 10 polymorphisms in ankylosing spondylitis

Genetic polymorphisms of the IL10 promoter region have been implicated in many autoimmune diseases, including seronegative spondyloarthropathies. We studied three SNPs (IL10-1087,-824, and -597) and two microsafellites(IL10R and IL10G) lying within the promoter region of IL10 for association with susceptibility to and clinical manifestations of ankylosing spondylitis (AS), a common form of spondyloarthritis. Four hundred and sixty-eight individuals from 182 Finnish families affected with AS were studied. No association between individual IL10 promoter region polymorphisms or marker haplotype was observed with susceptibility to AS, but weak association was noted between the IL10-597 and -824 SNPs and age of disease onset (P= 0.01 for each SNP). The IL10.G4 allele was associated with BASFI (corrected for disease duration) (P= 0.03). We conclude that IL10 promoter polymorphisms have no significant effect on susceptibility to AS, but may play a minor role in determining age of disease onset and disease severity. © 2003 Nature Publishing Group All rights reserved.

Enhancing information about sustainability features for sustainable housing delivery

Sustainability practices in government regulations and within the society influence the delivery of sustainable housing. The actual delivery rate of Australian sustain-able housing is not as high as other countries. There is an absence of engagement by stakeholders in adopting sustainable housing practices. This may be due, in the current Australian property market, to confusion as to what sustainability features should be considered, given the large range of environmental, economic and social sustainability options possible. One of the main problems appears to be that information demanders, especially real estate agents, valuers, insurance agents and mortgage lenders do not include sustainability perspectives in their advice or in their decision processes. Information distribution in the Australian property market is flawed, resulting in a lack of return-on-investment value of ‘green’ features implemented by some stakeholders. This paper reviewed the global sustainable development concept and Australian sustainable assessment methods. This review identified the possibility of a research project which aimed at identifying and integrating different perceptions and priority needs of the information demanders, for developing a model for the potential implementation of sustainability features distribution in the property industry. This research will reduce confusion on the sustainability-related information which can influence the decision making of stakeholders in the supply and demand of sustainable housing.

Place making facilitators of knowledge and innovation spaces: Insights from European best practices

Knowledge economy seeks its nourishment from diversity and dissemination of ideas and creativity of its talent base. This has led to the acknowledgement of place making as a major strategy to attract and retain the knowledge base into the emerging knowledge and innovation spaces. The study seeks to explore the adoption of place making in this context. Literature and practice provide information to understand the evolution of various spatial typologies and the specialised role of place making in such locations. This helps in determining the key facilitators of place making. The paper takes an interdisciplinary approach and develops an integrated conceptual framework considering dimensions and facilitators of place making. Through the lens of the framework, best practices across Europe—i.e., Cambridge Science Park (UK), 22@Barcelona (Spain), Arabianranta (Finland), Strijp-S (Netherlands), and Digital Hub (Ireland)—are scrutinised to highlight various approaches to place making. The findings provide insights and a discussion into the interplay of form, function, image and underlying processes in globally emerging spatial typologies of contemporary knowledge and innovation spaces.

Understanding the use of a bug tracking system in a global software development setup

Bug fixing is a highly cooperative work activity where developers, testers, product managers and other stake-holders collaborate using a bug tracking system. In the context of Global Software Development (GSD), where software development is distributed across different geographical locations, we focus on understanding the role of bug trackers in supporting software bug fixing activities. We carried out a small-scale ethnographic fieldwork in a software product team distributed between Finland and India at a multinational engineering company. Using semi-structured interviews and in-situ observations of 16 bug cases, we show that the bug tracker 1) supported information needs of different stake holder, 2) established common-ground, and 3) reinforced issues related to ownership, performance and power. Consequently, we provide implications for design around these findings.

An analysis of TLS handshake proxying

Content delivery networks (CDNs) are an essential component of modern website infrastructures: edge servers located closer to users cache content, increasing robustness and capacity while decreasing latency. However, this situation becomes complicated for HTTPS content that is to be delivered using the Transport Layer Security (TLS) protocol: the edge server must be able to carry out TLS handshakes for the cached domain. Most commercial CDNs require that the domain owner give their certificate's private key to the CDN's edge server or abandon caching of HTTPS content entirely. We examine the security and performance of a recently commercialized delegation technique in which the domain owner retains possession of their private key and splits the TLS state machine geographically with the edge server using a private key proxy service. This allows the domain owner to limit the amount of trust given to the edge server while maintaining the benefits of CDN caching. On the performance front, we find that latency is slightly worse compared to the insecure approach, but still significantly better than the domain owner serving the content directly. On the security front, we enumerate the security goals for TLS handshake proxying and identify a subtle difference between the security of RSA key transport and signed-Diffie--Hellman in TLS handshake proxying; we also discuss timing side channel resistance of the key server and the effect of TLS session resumption.

The effect of ground leases on house prices in Helsinki

One imperfection in housing markets is imperfect knowledge about legal interests such as ground leases. Both actual reduced legal interest as well as uncertainty surrounding rights and future lease payments for houses constructed on leased land may affect prices relative to houses built on freehold land. We use regression analysis of sales prices of condominium transactions in Helsinki to examine the effect ground leases have on house prices. We find that prices on condominiums constructed on leased lots are discounted at least 5 %, on average. In addition, we see that the announcement of potentially large increases in base rents upon renewal contributes to the discount.

Social and physical environments in senior communities: The Finnish experience

Purpose – The purpose of this paper is to discuss residents’ views of social and physical environments in a co-housing and in a senior housing setting in Finland. Also, the study aims to point out important connections between well-being and built environment. Design/methodology/approach – The data include interviews and survey responses gathered in the cases. The results and analysis are presented at different case study levels, with the discussion and conclusions following this. Findings – The findings show that the physical environment and common areas have an important role to activate residents. When well-designed common areas exist, a higher level of engagement can be achieved by getting residents involved in the planning and running of activities. Research limitations/implications – This paper discusses residents’ experiences in two Finnish housing settings and it focuses on the housing market in Finland. Practical implications – The findings encourage investors and housing operators to design and invest common areas which could activate residents and create social contacts. Also, investors have to pay attention to the way these developments are managed. Originality/value – This study is the first to investigate the Finnish co-housing setting and compare social and physical environments in a co-housing and a senior house.

Finnish seniors’ move to a senior house: Examining the push and pull factors

The purpose of this article is to explore the factors influencing residential decisions of Finnish seniors. Analysis draws on qualitative data gathered from in-depth interviews and open-ended survey questions completed by 37 seniors living in three independent living facilities in Finland. Content analysis was used to identify key factors pushing residents out of their former living situations and pulling them into their respective independent living facility. Analysis indicates that different senior houses attract different types of residents. Nevertheless, as a group, they reported similar motivational factors relating to community, physical, and social environments and to their personal circumstances.

The potential for consumer segmentation in the Finnish housing market

This article examines whether cluster analysis can be used to identify groups of Finnish residents with similar housing preferences. Because homebuilders in Finland have been providing relatively homogeneous products to an increasingly diverse population, current housing may not represent the occupiers' preferences so a segmentation approach relying on socioeconomic characteristics and expressed preferences may not be sufficient. We use data collected via questionnaire in a principal component analysis followed by a hierarchical cluster analysis to determine whether different combinations of housing attributes are important to groups of residents. We can identify four clusters of housing residents based on important characteristics when looking for a house. The clusters describe Finnish people in different phases of the life cycle and with different preferences based on their recreational activities and financial expenditures. Mass customization of housing could be used to better appeal to these different clusters of consumers who share similar preferences, increasing consumer satisfaction and improving profitability.

A high-density association screen of 155 ion transport genes for involvement with common migraine

The clinical overlap between monogenic Familial Hemiplegic Migraine (FHM) and common migraine subtypes, and the fact that all three FHM genes are involved in the transport of ions, suggest that ion transport genes may underlie susceptibility to common forms of migraine. To test this leading hypothesis, we examined common variation in 155 ion transport genes using 5257 single nucleotide polymorphisms (SNPs) in a Finnish sample of 841 unrelated migraine with aura cases and 884 unrelated non-migraine controls. The top signals were then tested for replication in four independent migraine case-control samples from the Netherlands, Germany and Australia, totalling 2835 unrelated migraine cases and 2740 unrelated controls. SNPs within 12 genes (KCNB2, KCNQ3, CLIC5, ATP2C2, CACNA1E, CACNB2, KCNE2, KCNK12, KCNK2, KCNS3, SCN5A and SCN9A) with promising nominal association (0.00041 < P < 0.005) in the Finnish sample were selected for replication. Although no variant remained significant after adjusting for multiple testing nor produced consistent evidence for association across all cohorts, a significant epistatic interaction between KCNB2 SNP rs1431656 (chromosome 8q13.3) and CACNB2 SNP rs7076100 (chromosome 10p12.33) (pointwise P = 0.00002; global P = 0.02) was observed in the Finnish case-control sample. We conclude that common variants of moderate effect size in ion transport genes do not play a major role in susceptibility to common migraine within these European populations, although there is some evidence for epistatic interaction between potassium and calcium channel genes, KCNB2 and CACNB2. Multiple rare variants or trans-regulatory elements of these genes are not ruled out.

Consistently replicating locus linked to migraine on 10q22-q23

Here, we present the results of two genome-wide scans in two diverse populations in which a consistent use of recently introduced migraine-phenotyping methods detects and replicates a locus on 10q22-q23, with an additional independent replication. No genetic variants have been convincingly established in migraine, and although several loci have been reported, none of them has been consistently replicated. We employed the three known migraine-phenotyping methods (clinical end diagnosis, latent-class analysis, and trait-component analysis) with robust multiple testing correction in a large sample set of 1675 individuals from 210 migraine families from Finland and Australia. Genome-wide multipoint linkage analysis that used the Kong and Cox exponential model in Finns detected a locus on 10q22-q23 with highly significant evidence of linkage (LOD 7.68 at 103 cM in female-specific analysis). The Australian sample showed a LOD score of 3.50 at the same locus (100 cM), as did the independent Finnish replication study (LOD score 2.41, at 102 cM). In addition, four previously reported loci on 8q21, 14q21, 18q12, and Xp21 were also replicated. A shared-segment analysis of 10q22-q23 linked Finnish families identified a 1.6-9.5 cM segment, centered on 101 cM, which shows in-family homology in 95% of affected Finns. This region was further studied with 1323 SNPs. Although no significant association was observed, four regions warranting follow-up studies were identified. These results support the use of symptomology-based phenotyping in migraine and suggest that the 10q22-q23 locus probably contains one or more migraine susceptibility variants.

Genetic and environmental influences on migraine: a twin study across six countries

Migraine is a common neurovascular brain disorder that is manifested in recurrent episodes of disabling headache. The aim of the present study was to compare the prevalence and heritability of migraine across six of the countries that participate in GenomEUtwin project including a total number of 29,717 twin pairs. Migraine was assessed by questionnaires that differed between most countries. It was most prevalent in Danish and Dutch females (32% and 34%, respectively), whereas the lowest prevalence was found in the younger and older Finnish cohorts (13% and 10%, respectively). The estimated genetic variance (heritability) was significant and the same between sexes in all countries. Heritability ranged from 34% to 57%, with lowest estimates in Australia, and highest estimates in the older cohort of Finland, the Netherlands, and Denmark. There was some indication that part of the genetic variance was non-additive, but this was significant in Sweden only. In addition to genetic factors, environmental effects that are non-shared between members of a twin pair contributed to the liability of migraine. After migraine definitions are homogenized among the participating countries, the GenomEUtwin project will provide a powerful resource to identify the genes involved in migraine.