Cardiovascular disease is increased prior to onset of rheumatoid arthritis but not osteoarthritis: The population-based Nord-Trøndelag health study (HUNT)

Introduction: Patients with rheumatoid arthritis (RA) have increased risk of cardiovascular (CV) events. We sought to test the hypothesis that due to increased inflammation, CV disease and risk factors are associated with increased risk of future RA development. Methods: The population-based Nord-Trøndelag health surveys (HUNT) were conducted among the entire adult population of Nord-Trøndelag, Norway. All inhabitants 20 years or older were invited, and information was collected through comprehensive questionnaires, a clinical examination, and blood samples. In a cohort design, data from HUNT2 (1995-1997, baseline) and HUNT3 (2006-2008, follow-up) were obtained to study participants with RA (n = 786) or osteoarthritis (n = 3,586) at HUNT3 alone, in comparison with individuals without RA or osteoarthritis at both times (n = 33,567). Results: Female gender, age, smoking, body mass index, and history of previous CV disease were associated with self-reported incident RA (previous CV disease: odds ratio 1.52 (95% confidence interval 1.11-2.07). The findings regarding previous CV disease were confirmed in sensitivity analyses excluding participants with psoriasis (odds ratio (OR) 1.70 (1.23-2.36)) or restricting the analysis to cases with a hospital diagnosis of RA (OR 1.90 (1.10-3.27)) or carriers of the shared epitope (OR 1.76 (1.13-2.74)). History of previous CV disease was not associated with increased risk of osteoarthritis (OR 1.04 (0.86-1.27)). Conclusion: A history of previous CV disease was associated with increased risk of incident RA but not osteoarthritis.

Effects of PTPN22 C1858T polymorphism on susceptibility and clinical characteristics of British Caucasian rheumatoid arthritis patients

Objectives. To confirm the association of a functional single-nucleotide polymorphism (SNP), C1858T (rs2476601), in the PTPN22 gene of British Caucasian rheumatoid arthritis (RA) patients and to evaluate its influence on the RA phenotype. Methods. A total of 686 RA patients and 566 healthy volunteers, all of British Caucasian origin, were genotyped for C1858T polymorphism by PCR-restriction fragment length polymorphism assay. Data were analysed using SPSS software and the χ 2 test as applicable. Results. The PTPN22 1858T risk allele was more prevalent in the RA patients (13.9%) compared with the healthy controls (10.3%) (P = 0.008, odds ratio 1.4, 95% confidence interval 1.09-1.79). The association of the T allele was restricted to those with rheumatoid factor (RF)-positive disease (n = 524, 76.4%) (P = 0.004, odds ratio 1.5, 95% confidence interval 1.1-1.9). We found no association between PTPN22 and the presence of the HLA-DRB1 shared epitope or clinical characteristics. Conclusions. We confirmed the previously reported association of PTPN22 with RF-positive RA, which was independent from the HLA-DRB1 genotype.

Non-inherited maternal HLA alleles are associated with rheumatoid arthritis

Background. Rheumatoid arthritis (RA) is strongly associated with a series of HLA-DRB1 alleles that encode a conserved sequence of amino acids (70Q/R K/R R A A74) in the DRβ1 chain, known as the shared epitope (SE). However 30% of patients are negative for DRB1*04 and 15% are SE-negative. Exposure to these alleles as non-inherited maternal antigens (NIMA) might explain this discrepancy. We undertook a family study to investigate the role of NIMA in RA. Methods. One hundred families, including the RA proband and both parents, were recruited. HLA-DRB1 genotyping was performed using an allele-specific polymerase chain reaction by standard methods. The frequencies of NIMA and non-inherited paternal antigens (NIPA) were compared using contingency tables and a two-tailed P test. We then reviewed four previously published studies of NIMA in RA and conducted an analysis of the combined data Results. We identified 36 families in which the proband was DRB1*04-negative and 13 in which the proband lacked the SE. There was an excess of DRB1*04 and SE NIMA (P=0.05) compared with NIPA. Combined analysis with previous studies showed that 53/231 mothers (23%) versus 25/205 fathers (12%) had a non-inherited DRB1*04 (P=0.003) and 30/99 mothers versus 18/101 fathers had a non-inherited SE allele (P=0.03). Conclusion. A role for HLA NIMA in RA is suggested by these results.

HLA-DR/DQ haplotype in rheumatoid arthritis: Novel allelic associations in UK Caucasians

Objective. To elucidate the relative importance of the HLA-DR and HLA-DQ loci in conferring genetic predisposition to rheumatoid arthritis (RA). Methods. HLA-DRB1 and HLA-DQB1 alleles were typed in a set of 685 patients with RA using sequence-specific polymerase chain reaction. Allele and phenotype frequencies were compared with those in 2 large sets of historical, ethnically matched healthy controls, using the relative predispositional effect method. Results. Positive association was confirmed with the shared epitope positive HLA-DRB1 alleles associated with RA in Caucasians. A significant susceptibility effect was observed with HLA-DRB1*09, described in other ethnically diverse populations but not in Caucasians. A significant underrepresentation of the HLA-DRB1*0103 variant was noted among the RA cases, supporting the proposed protective role of the DERAA motif at residues 70-74 of the DRβ molecule. No HLA-DRB1 independent association of the HLA-DQB1 alleles, implicated in predisposing to RA, was evident. Conclusion. These data corroborate the shared epitope hypothesis of susceptibility to RA and provide strong evidence for the DRB1 locus as the primary RA susceptibility factor in the HLA region.

Polymorphism in codon 17 of the CTLA-4 gene (+49 A/G) is not associated with susceptibility to rheumatoid arthritis in British Caucasians

The role of the CTLA-4 antigen in the development of autoimmune diseases is well documented, with several autoimmune disorders showing association or linkage with the CTLA-4 locus. Its role in the aetiology of rheumatoid arthritis (RA) however, remains unclear, as the functional studies of the B7-CTLA-4 pathway in mouse models of RA and genetic studies in humans have given contrasting results. We have studied the single nucleotide polymorphism at position +49 (A/G) of the CTLA-4 gene, in a cohort of 421 RA cases and 452 healthy controls from the UK. Despite the high statistical power to detect even a weak susceptibility effect, no significant association was found. We also analysed the distribution of the allele and genotype frequencies with respect to the presence of the shared epitope (a known RA susceptibility factor) and found no statistically significant differences. We conclude that, although the importance of the B7-CTLA-4 interaction in the development of RA can not be excluded, the CTLA-4 gene is unlikely to be a predisposing factor to this disease.

Assessing the potential of inter-organisational shared services

Shared Services (SS) involves the convergence and streamlining of an organisation’s functions to ensure timely service delivery as effectively and efficiently as possible. As a management structure designed to promote value generation, cost savings and improved service delivery by leveraging on economies of scale, the idea of SS is driven by cost reduction and improvements in quality levels of service and efficiency. Current conventional wisdom is that the potential for SS is increasing due to the increasing costs of changing systems and business requirements for organisations and in implementing and running information systems. In addition, due to commoditisation of large information systems such as enterprise systems, many common, supporting functions across organisations are becoming more similar than not, leading to an increasing overlap in processes and fuelling the notion that it is possible for organisations to derive benefits from collaborating and sharing their common services through an inter-organisational shared services (IOSS) arrangement. While there is some research on traditional SS, very little research has been done on IOSS. In particular, it is unclear what are the potential drivers and inhibitors of IOSS. As the concepts of IOSS and SS are closely related to that of Outsourcing, and their distinction is sometimes blurred, this research has the first objective of seeking a clear conceptual understanding of the differences between SS and Outsourcing (in motivators, arrangements, benefits, disadvantages, etc) and based on this conceptual understanding, the second objective of this research is to develop a decision model (Shared Services Potential model) which would aid organisations in deciding which arrangement would be more appropriate for them to adopt in pursuit of process improvements for their operations. As the context of the study is on universities in higher education sharing administrative services common to or across them and with the assumption that such services were homogenous in nature, this thesis also reports on a case study. The case study involved face to face interviews from representatives of an Australian university to explore the potential for IOSS. Our key findings suggest that it is possible for universities to share services common across them as most of them were currently using the same systems although independently.

A novel nonrepudiable threshold multi-proxy multi-signature scheme with shared verification

Tzeng et al. proposed a new threshold multi-proxy multi-signature scheme with threshold verification. In their scheme, a subset of original signers authenticates a designated proxy group to sign on behalf of the original group. A message m has to be signed by a subset of proxy signers who can represent the proxy group. Then, the proxy signature is sent to the verifier group. A subset of verifiers in the verifier group can also represent the group to authenticate the proxy signature. Subsequently, there are two improved schemes to eliminate the security leak of Tzeng et al.’s scheme. In this paper, we have pointed out the security leakage of the three schemes and further proposed a novel threshold multi-proxy multi-signature scheme with threshold verification.

Understanding Shared Services : an exploration of the IS literature

In a competitive environment, companies continuously innovate to offer superior services at lower costs. ‘Shared services’ have been extensively adopted in practice as one means for improving organisational performance. Shared services is considered most appropriate for support functions, and is widely adopted in Human Resource Management, Finance and Accounting; more recently being employed across the Information Systems function. IS applications and infrastructure are an important enabler and driver of shared services in all functional areas. As computer based corporate information systems have become de facto and the internet pervasive and increasingly the backbone of administrative systems, the technical impediments to sharing have come down dramatically. As this trend continues, CIOs and IT professionals will need a deeper understanding of the shared services phenomenon and its implications. The advent of shared services has consequential implications for the IS academic discipline. Yet, archival analysis of IS the academic literature reveals that shared services, though mentioned in more than 100 articles, has received little in depth attention. This paper is the first attempt to investigate and report on the current status of shared services in the IS literature. The paper presents detailed review of literature from main IS journals and conferences, findings evidencing a lack of focus and definitions and objectives lacking conceptual rigour. The paper concludes with a tentative operational definition, a list of perceived main objectives of shared services, and an agenda for related future research.

Shared leadership in Queensland schools : a collective case study

Shared leadership has been identified as a key governance base for the future of government and Catholic schools in Queensland, the state’s two largest providers of school education. Shared leadership values the contributions that many individuals can make through collaboration and teamwork. It claims to improve organisational performance and reduce the increasing pressures faced by principals. However despite these positive features, shared leadership is generally not well understood, not well accepted and not valued by those who practice or study leadership. A collective case study method was chosen, incorporating a series of semi-structured interviews with principals and the use of official school documents. The study has explored the current understanding and practice of shared leadership in four Queensland schools and investigated its potential for use.

Dragline automation - a decade of development : shared autonomy for improving mining equipment productivity

Draglines are massive machines commonly used in surface mining to strip overburden, revealing the targeted minerals for extraction. Automating some or all of the phases of operation of these machines offers the potential for significant productivity and maintenance benefits. The mining industry has a history of slow uptake of automation systems due to the challenges contained in the harsh, complex, three-dimensional (3D), dynamically changing mine operating environment. Robotics as a discipline is finally starting to gain acceptance as a technology with the potential to assist mining operations. This article examines the evolution of robotic technologies applied to draglines in the form of machine embedded intelligent systems. Results from this work include a production trial in which 250,000 tons of material was moved autonomously, experiments demonstrating steps towards full autonomy, and teleexcavation experiments in which a dragline in Australia was tasked by an operator in the United States.