Association between the interleukin 23 receptor and ankylosing spondylitis is confirmed by a new UK case-control study and meta-analysis of published series

Objectives. It has been shown previously that IL-23R variants are associated with AS. We conducted an extended analysis in the UK population and a meta-analysis with the previously published studies, in order to refine these IL-23R associations with AS. Methods. The UK case-control study included 730 new cases and 1331 healthy controls. In the extended study, the 730 cases were combined with 1088 published cases. Allelic associations were analysed using contingency tables. In the meta-analysis, 3482 cases and 3150 controls from four different published studies and the new UK cases were combined. DerSimonian-Laird test was used to calculate random effects pooled odds ratios (ORs). Results. In the UK case-control study with new cases, four of the eight SNPs showed significant associations, whereas in the extended UK study, seven of the eight IL-23R SNPs showed significant associations (P < 0.05) with AS, maximal with rs11209032 (P < 10-5, OR 1.3), when cases with IBD and/or psoriasis were excluded. The meta-analysis showed significant associations with all eight SNPs; the strongest associations were again seen not only with rs11209032 (P = 4.06 × 10-9, OR ∼1.2) but also with rs11209026 (P < 10-10, OR ∼0.6). Conclusions. IL-23R polymorphisms are clearly associated with AS, but the primary causal association(s) is(are) still not established. These polymorphisms could contribute either increased or decreased susceptibility to AS; functional studies will be required for their full evaluation. Additionally, observed stronger associations with SNPs rs11209026 and rs11465804 upon exclusion of IBD and/or psoriasis cases may represent an independent association with AS. © The Author 2009. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.

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.

New mobilities for accessible cities: Toward scenarios for seamless journeys

While cities increasingly attest to plans to make their resources accessible for people with disabilities, the realities of achieving the travel considered integral to urban life continue to be frustrating and prohibitive for this group. Accessing the basic opportunities of contemporary urban life now presupposes the supports and resources afforded by new mobilities, combining virtual and actual travel and communication in negotiating our work, leisure, connections with families and culture. For the researchers applying the new mobilities paradigm, this requires a focus which is suited to capturing movement and its spatial and temporal coordinates and should also turn to illuminate the darker side of these relationships: coerced immobility experienced by people with disabilities. This chapter discusses an approach to research and the development of design scenarios – concepts emerging from research that may inform design - that take seriously the role of movement, time and space in the achievement of valued connections by individuals with disabilities with particular reference to the journey to work. In particular we apply, in a case study, concepts of time and space that are relevant to the in situ experience of getting to work; raising questions regarding the way getting ready and travelling are experienced in the context of risk and contingency and the actual and potential role of the technical, material and social environment. We then respond to the analysis of this case with a discussion about the way emergent scenarios can imagine “possible or preferable futures” for the mobile citizenship of people with disabilities.

Lawyers linked to litigation funding face court censure: Bolitho v Banksia Securities Limited (No.4) [2014] VSC 582

In Bolitho v Banksia Securities Limited (No 4) [2014] VSC 582 the Supreme Court of Victoria concluded that the proper administration of justice, including the appearance of justice, required that the lawyers representing the plaintiff in the group proceeding should be restrained from continuing to act for the plaintiff. This Victorian case illustrates how courts are likely to respond when lawyers attempt to circumvent the prohibition on contingency fees through litigation funding in which they have a financial interest.

Drivers of the accuracy of developers' early stage cost estimates in residential construction

Purpose – Preliminary cost estimates for construction projects are often the basis of financial feasibility and budgeting decisions in the early stages of planning and for effective project control, monitoring and execution. The purpose of this paper is to identify and better understand the cost drivers and factors that contribute to the accuracy of estimates in residential construction projects from the developers’ perspective. Design/methodology/approach – The paper uses a literature review to determine the drivers that affect the accuracy of developers’ early stage cost estimates and the factors influencing the construction costs of residential construction projects. It used cost variance data and other supporting documentation collected from two case study projects in South East Queensland, Australia, along with semi-structured interviews conducted with the practitioners involved. Findings – It is found that many cost drivers or factors of cost uncertainty identified in the literature for large-scale projects are not as apparent and relevant for developers’ small-scale residential construction projects. Specifically, the certainty and completeness of project-specific information, suitability of historical cost data, contingency allowances, methods of estimating and the estimator’s level of experience significantly affect the accuracy of cost estimates. Developers of small-scale residential projects use pre-established and suitably priced bills of quantities as the prime estimating method, which is considered to be the most efficient and accurate method for standard house designs. However, this method needs to be backed with the expertise and experience of the estimator. Originality/value – There is a lack of research on the accuracy of developers’ early stage cost estimates and the relevance and applicability of cost drivers and factors in the residential construction projects. This research has practical significance for improving the accuracy of such preliminary cost estimates.

Dealing with discomfort: How the unspeakable confounds wicked planning problems

The idea of ‘wicked’ problems has made a valuable contribution to recognising the complexity and challenges of contemporary planning. However, some wicked policy problems are further complicated by a significant moral, psychological, religious or cultural dimension. This is particularly the case for problems that possess strong elements of abjection and symbolic pollution and high degrees of psychosocial sensitivity. Because this affects the way these problems are framed and discussed they are also characterised by high levels of verbal proscription. As a result, they are not discussed in the rational and emotion-free way that conventional planning demands and can become obscured or inadequately acknowledged in planning processes. This further contributes to their wickedness and intractability. Through paradigmatic urban planning examples, we argue that placing their unspeakable nature at the forefront of enquiry will enable planners to advocate for a more contextually and culturally situated approach to planning, which accommodates both emotional and embodied talk alongside more technical policy contributions. Re-imagining wicked problems in this way has the potential to enhance policy and plan-making and to disrupt norms, expose their contingency, and open new ways of planning for both the unspeakable and the merely wicked.

Is there a role for microsampling in antibiotic pharmacokinetic studies?

- Introduction Clinical pharmacokinetic studies of antibiotics can establish evidence-based dosing regimens that improve the likelihood of eradicating the pathogen at the site of infection, reduce the potential for selection of resistant pathogens, and minimize harm to the patient. Innovations in small volume sampling (< 50 μL) or ‘microsampling’ may result in less-invasive sample collection, self-sampling and dried storage. Microsampling may open up opportunities in patient groups where sampling is challenging. - Areas Covered The challenges for implementation of microsampling to assure suitability of the results, include: acceptable study design, regulatory agency acceptance, and meeting bioanalytical validation requirements. This manuscript covers various microsampling methods, including dried blood/plasma spots, volumetric absorptive microsampling, capillary microsampling, plasma preparation technologies and solid-phase microextraction. - Expert Opinion The available analytical technology is being underutilized due to a lack of bridging studies and validated bioanalytical methods. These deficiencies represent major impediments to the application of microsampling to antibiotic pharmacokinetic studies. A conceptual framework for the assessment of the suitability of microsampling in clinical pharmacokinetic studies of antibiotics is provided. This model establishes a ‘contingency approach’ with consideration of the antibiotic and the type and location of the patient, as well as the more prescriptive bioanalytical validation protocols.