CCL2 and CCR2 regulate pain-related behaviour and early gene expression in post-traumatic murine osteoarthritis but contribute little to chondropathy

SummaryObjectiveThe role of inflammation in structural and symptomatic osteoarthritis (OA) remains unclear. One key mediator of inflammation is the chemokine CCL2, primarily responsible for attracting monocytes to sites of injury. We investigated the role of CCL2 and its receptor CCR2 in experimental OA.DesignOA was induced in 10 weeks old male wild type (WT), Ccl2−/− and Ccr2−/− mice, by destabilisation of the medial meniscus (DMM). RNA was extracted from whole joints at 6 h and 7 days post-surgery and examined by reverse transcription polymerase chain reaction (RT-PCR). Gene expression changes between naïve and DMM-operated mice were compared. Chondropathy scores, from mice at 8, 12, 16 and 20 weeks post DMM were calculated using modified Osteoarthritis Research Society International (OARSI) grading systems. Changes in hind paw weight distribution, as a measure of pain, were assessed by Linton incapacitance.ResultsAbsence of CCL2 strongly suppressed (>90%) selective inflammatory response genes in the joint 6 h post DMM, including arginase 1, prostaglandin synthase 2, nitric oxide synthase 2 and inhibin A. IL6, MMP3 and tissue inhibitor of metalloproteinase 1 were also significantly suppressed. Similar trends were also observed in the absence of CCR2. A lower average chondropathy score was observed in both Ccl2−/− and Ccr2−/− mice at 12, 16 and 20 weeks post DMM compared with WT mice, but this was only statistically significant at 20 weeks in Ccr2−/− mice. Pain-related behaviour in Ccl2−/− and Ccr2−/− mice post DMM was delayed in onset.ConclusionThe CCL2/CCR2 axis plays an important role in the development of pain in murine OA, but contributes little to cartilage damage

The local socio-economic impacts of major power station projects

The Impacts Assessment Unit (IAU) at Oxford Brookes University has pioneered research on the local socio-economic impacts of major power station projects. Resultant insights have included: • Increasing focus on socio-economic impacts in the assessments of such projects; • Use of associated planning techniques and mitigation measures; and • Use of the research by wide range of stakeholders, including developers, local communities, local authorities and various agencies (e.g. health, education etc). Within the REF period these insights have been deployed in new power station impact research, recently (2011-2013) forming part of the successful EDF (international electricity utility company www.edf.com) application to the Infrastructure Planning Commission (IPC) (now National Infrastructure Directorate within the UK Planning Inspectorate (PINS)) to build a new nuclear power station Hinkley Point C (Somerset), plus consultation studies for a new nuclear power station Sizewell C (Suffolk)

Reducing green tape or rolling back IA in Australia: What are found jurisdictions up to?

EIA has been practiced in Australia and the rest of the world for over 40 years, but despite its successes, EIA may now be facing its biggest challenge since it came into being in 1970 with the US National Environmental Policy Act. As Morgan (2012, 11) notes: “As governments look to stimulate economic growth and create employment in response to the current financial crisis, many are promoting a major expansion of physical infrastructure, encouraging resource development projects, and generally seeking to speed decision-making about development projects. Both EIA and SEA should be even more important in such circumstances, yet the moves taken in some countries to speed up decision-making may weaken the provisions for environmental protection, including impact assessment.” In this political and economic environment, EIA is under scrutiny. Proposed changes to the EU directive on EIA released in October 2012 contain ten changes to the Articles of the Directive, with six of these referring to either ‘streamlining’ EIA or introducing specific timeframes for parts of the EIA process (European Commission 2012). This scrutiny has not been restricted to economies in recession, but includes those that have avoided recession because of strong resources sectors. The same appears to be happening in Australia, and this paper reports on these and other possible ‘efficiency’ changes to EIA in Australia at both national and sub-national levels. We attempt to critically examine the nature of such changes and the risks that may be associated with their implementation. Changes to three of the sub-national EIA processes are reviewed in detail, as well as the proposed changes to the national EIA process. There is always room for more timely assessments, but a critical examination of the potential consequences of these “reforms” on the conduct of EIAs is needed, including whether these efficiency changes will deliver sound environmental management and sustainability-oriented decision-making

Unrestricted Hartree-Fock theory of Wigner crystals

We demonstrate that unrestricted Hartree-Fock theory applied to electrons in a uniform potential has stable Wigner crystal solutions for $r_s \geq 1.44$ in two dimensions and $r_s \geq 4.5$ in three dimensions. The correlation energies of the Wigner crystal phases are considerably smaller than those of the fluid phases at the same density.Comment: 4 pages, 5 figure

The moral-IT deck:A tool for ethics by design

This paper presents the design process and empirical evaluation of a new tool for enabling ethics by design: The Moral-IT Cards. Better tools are needed to support the role of technologists in addressing ethical issues during system design. These physical cards support reflection by technologists on normative aspects of technology development, specifically on emerging risks, appropriate safeguards and challenges of implementing these in the system. We discuss how the cards were developed and tested within 5 workshops with 20 participants from both research and commercial settings. We consider the role of technologists in ethics from different EU/UK policymaking initiatives and disciplinary perspectives (i.e. Science and Technology Studies (STS), IT Law, Human Computer Interaction (HCI), Computer/Engineering Ethics). We then examine existing ethics by design tools, and other cards based tools before arguing why cards can be a useful medium for addressing complex ethical issues. We present the development process for the Moral-IT cards, document key features of our card design, background on the content, the impact assessment board process for using them and how this was formulated. We discuss our study design and methodology before examining key findings which are clustered around three overarching themes. These are: the value of our cards as a tool, their impact on the technology design process and how they structure ethical reflection practices. We conclude with key lessons and concepts such as how they level the playing field for debate; enable ethical clustering, sorting and comparison; provide appropriate anchors for discussion and highlighted the intertwined nature of ethics.Comment: Governance and Regulation; Design Tools; Responsible Research and Innovation; Ethics by Design; Games; Human Computer Interaction, Card Based Tool

Intermittent applied mechanical loading induces subchondral bone thickening that may be intensified locally by contiguous articular cartilage lesions

Objectives: Changes in subchondral bone (SCB) and cross-talk with articular cartilage (AC) have been linked to osteoarthritis (OA). Using micro-computed tomography (micro-CT) this study: (1) examines changes in SCB architecture in a non-invasive loading mouse model in which focal AC lesions are induced selectively in the lateral femur, and (2) determines any modifications in the contralateral knee, linked to changes in gait, which might complicate use of this limb as an internal control. Methods: Right knee joints of CBA mice were loaded: once with 2weeks of habitual use (n=7), for 2weeks (n=8) or for 5weeks (n=5). Both left (contralateral) and right (loaded) knees were micro-CT scanned and the SCB and trabecular bone analysed. Gait analysis was also performed. Results: These analyses showed a significant increase in SCB thickness in the lateral compartments in joints loaded for 5weeks, which was most marked in the lateral femur; the contralateral non-loaded knee also showed transient SCB thickening (loaded once and repetitively). Epiphyseal trabecular bone BV/TV and trabecular thickness were also increased in the lateral compartments after 5 weeks of loading, and in all joint compartments in the contralateral knee. Gait analysis showed that applied loading only affected gait in the contralateral himd-limb in all groups of mice from the second week after the first loading episode. Conclusions: These data indicate a spatial link between SCB thickening and AC lesions following mechanical trauma, and the clear limitations associated with the use of contralateral joints as controls in such OA models, and perhaps in OA diagnosis

The place of strategic environmental assessment in the privatised electricity industry

The private sector has given relatively little attention to the emergence of strategic environmental assessment (SEA); even recently privatised utilities, where SEA might be deemed particularly appropriate, and whose activities are likely to fall within the scope of the European Union SEA Directive, have shown less interest than might be expected. However, the global trend towards the privatisation of state-owned enterprises makes the adaptation of SEA towards these industries all the more pressing. This paper addresses the place that SEA might take within the electricity sector, taking the privatised UK electricity industry as an example. Particular challenges are posed by the radical restructuring of the industry, designed to introduce competitive behaviour, making the development of comprehensive SEA processes problematic, and requiring SEA to be placed in the context of corporate environmental policy and objectives.</p