Wheel running from a juvenile age delays onset of specific motor deficits but does not alter protein aggregate density in a mouse model of Huntington's disease

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background Huntington's disease (HD) is a neurodegenerative disorder predominantly affecting the cerebral cortex and striatum. Transgenic mice (R6/1 line), expressing a CAG repeat encoding an expanded polyglutamine tract in the N-terminus of the huntingtin protein, closely model HD. We have previously shown that environmental enrichment of these HD mice delays the onset of motor deficits. Furthermore, wheel running initiated in adulthood ameliorates the rear-paw clasping motor sign, but not an accelerating rotarod deficit. Results We have now examined the effects of enhanced physical activity via wheel running, commenced at a juvenile age (4 weeks), with respect to the onset of various behavioral deficits and their neuropathological correlates in R6/1 HD mice. HD mice housed post-weaning with running wheels only, to enhance voluntary physical exercise, have delayed onset of a motor co-ordination deficit on the static horizontal rod, as well as rear-paw clasping, although the accelerating rotarod deficit remains unaffected. Both wheel running and environmental enrichment rescued HD-induced abnormal habituation of locomotor activity and exploratory behavior in the open field. We have found that neither environment enrichment nor wheel running ameliorates the shrinkage of the striatum and anterior cingulate cortex (ACC) in HD mice, nor the overall decrease in brain weight, measured at 9 months of age. At this age, the density of ubiquitinated protein aggregates in the striatum and ACC is also not significantly ameliorated by environmental enrichment or wheel running. Conclusion These results indicate that enhanced voluntary physical activity, commenced at an early presymptomatic stage, contributes to the positive effects of environmental enrichment. However, sensory and cognitive stimulation, as well as motor stimulation not associated with running, may constitute major components of the therapeutic benefits associated with enrichment. Comparison of different environmental manipulations, performed in specific time windows, can identify critical periods for the induction of neuroprotective 'brain reserve' in animal models of HD and related neurodegenerative diseases.Published versio

The future of public sector accounting research. A polyphonic debate

PurposeThe purpose of this polyphonic paper is to report on interdisciplinary discussions on the state-of-the-art and future of public sector accounting research (PSAR). The authors hope to enliven the debates of the past and future developments in terms of context, themes, theories, methods and impacts in the field of PSAR by the exchanges they include here. Design/methodology/approachThis polyphonic paper adopts an interdisciplinary approach. It brings into conversation ideas, views and approaches of several scholars on the actual and future developments of PSAR in various contexts, and explores potential implications. FindingsThis paper has brought together scholars from a plurality of disciplines, research methods and geographical areas, showing at the same time several points of convergence on important future themes (such as accounting as a mean for public, accounting, hybridity and value pluralism) and enabling conditions (accounting capabilities, profession and digitalisation) for PSA scholarship and practice, and the richness of looking at them from a plurality of perspectives. Research limitations/implicationsExploring these past and future developments opens up the potential for interesting theoretical insights. A much greater theoretical and practical reconsideration of PSAR will be fostered by the exchanges included here. Originality/valueIn setting out a future research agenda, this paper fosters theoretical and methodological pluralism in the interdisciplinary research community interested in PSAR in various contexts. The discussion perspectives presented in this paper constitute not only a basis for further research in this relevant accounting area on the role, status and developments of PSAR but also creative potential for practitioners to be more reflective on their practices and also intended and united outcomes of such practices

Anomalous self-diffusion in the ferromagnetic Ising chain with Kawasaki dynamics

We investigate the motion of a tagged spin in a ferromagnetic Ising chain evolving under Kawasaki dynamics. At equilibrium, the displacement is Gaussian, with a variance growing as $A t^{1/2}$. The temperature dependence of the prefactor $A$ is derived exactly. At low temperature, where the static correlation length $\xi$ is large, the mean square displacement grows as $(t/\xi^2)^{2/3}$ in the coarsening regime, i.e., as a finite fraction of the mean square domain length. The case of totally asymmetric dynamics, where $(+)$ (resp. $(-)$) spins move only to the right (resp. to the left), is also considered. In the steady state, the displacement variance grows as $B t^{2/3}$. The temperature dependence of the prefactor $B$ is derived exactly, using the Kardar-Parisi-Zhang theory. At low temperature, the displacement variance grows as $t/\xi^2$ in the coarsening regime, again proportionally to the mean square domain length.Comment: 22 pages, 8 figures. A few minor changes and update

A conceptual framework and practical guide for assessing fitness-to-operate in the offshore oil and gas industry

The paper outlines a systemic approach to understanding and assessing safety capability in the offshore oil and gas industry. We present a conceptual framework and assessment guide for understanding fitness-to-operate (FTO) that builds a more comprehensive picture of safety capability for regulators and operators of offshore facilities. The FTO framework defines three enabling capitals that create safety capability: organizational capital, social capital, and human capital. For each type of capital we identify more specific dimensions based on current theories of safety, management, and organizational processes. The assessment guide matches specific characteristics to each element of the framework to support assessment of safety capability. The content and scope of the FTO framework enable a more comprehensive coverage of factors that influence short-term and long-term safety outcomes

New Dynamic Monte Carlo Renormalization Group Method

The dynamical critical exponent of the two-dimensional spin-flip Ising model is evaluated by a Monte Carlo renormalization group method involving a transformation in time. The results agree very well with a finite-size scaling analysis performed on the same data. The value of $z = 2.13 \pm 0.01$ is obtained, which is consistent with most recent estimates

From Providers to PHOs: an institutional analysis of nonprofit primary health care governance in New Zealand

Policy reforms to primary health care delivery in New Zealand required government-funded firms overseeing care delivery to be constituted as nonprofit entities with governance shared between consumer and producers. This paper examines the consumer and producer interests in the allocation of ownership and control of New Zealand firms delivering primary health care utilising theories of competition in the markets for ownership and control of firms. Consistent with pre-reform patterns of ownership and control provider interests appear to have exerted effective control over the formation and governance of the new entities in all but a few cases where community (consumer) control was already established. Their ability to do so is implied from the absence of a defined ownership stake via which the balance of governance control could shift as a consequence of changes to incentives facing the different stakeholding groups. It appears that the pre-existing patterns will prevail and further intervention will be required if policymakers are to achieve their underlying aims

Clinical use of HIV integrase inhibitors : a systematic review and meta-analysis

Background: Optimal regimen choice of antiretroviral therapy is essential to achieve long-term clinical success. Integrase inhibitors have swiftly been adopted as part of current antiretroviral regimens. The purpose of this study was to review the evidence for integrase inhibitor use in clinical settings. Methods: MEDLINE and Web-of-Science were screened from April 2006 until November 2012, as were hand-searched scientific meeting proceedings. Multiple reviewers independently screened 1323 citations in duplicate to identify randomized controlled trials, nonrandomized controlled trials and cohort studies on integrase inhibitor use in clinical practice. Independent, duplicate data extraction and quality assessment were conducted. Results: 48 unique studies were included on the use of integrase inhibitors in antiretroviral therapy-naive patients and treatment-experienced patients with either virological failure or switching to integrase inhibitors while virologically suppressed. On the selected studies with comparable outcome measures and indication (n = 16), a meta-analysis was performed based on modified intention-to-treat (mITT), on-treatment (OT) and as-treated (AT) virological outcome data. In therapy-naive patients, favorable odds ratios (OR) for integrase inhibitor-based regimens were observed, (mITT OR 0.71, 95% CI 0.59-0.86). However, integrase inhibitors combined with protease inhibitors only did not result in a significant better virological outcome. Evidence further supported integrase inhibitor use following virological failure (mITT OR 0.27; 95% CI 0.11-0.66), but switching to integrase inhibitors from a high genetic barrier drug during successful treatment was not supported (mITT OR 1.43; 95% CI 0.89-2.31). Integrase inhibitor-based regimens result in similar immunological responses compared to other regimens. A low genetic barrier to drug-resistance development was observed for raltegravir and elvitegravir, but not for dolutegravir. Conclusion: In first-line therapy, integrase inhibitors are superior to other regimens. Integrase inhibitor use after virological failure is supported as well by the meta-analysis. Careful use is however warranted when replacing a high genetic barrier drug in treatment-experienced patients switching successful treatment

Charity registration and reporting:a cross-Jurisdictional and theoretical analysis of regulatory impact

Increasingly governments worldwide regulate charities, seeking to restrict the number of organizations claiming taxation exemptions, reduce abuse of state support and fraud. Under public interest theory governments may increase philanthropy through public trust and confidence in charities. Under public choice theory regulators will maximize political returns, ‘manage’ charity-government relationships, and avoid regulatory capture. Phillips and Smith (2014) suggest that charities’ regulatory regimes should coalesce, despite jurisdictional diversity. We analyse charity regulatory regimes against underlining theories of regulation, and assess regulatory costs and benefits. Thus regulators can reduce regulatory inefficiency, and balance accountability and transparency demands with charities’ abilities to deliver

The State Relationship with Religion:defined through disciplinary procedures of accounting and regulation

State regulation of charities is increasing. Nevertheless, although religious entities also pursue charitable objectives, jurisdictions often regulate them differently. In some states (including England until recently), the church (religious charities) are not called to account for their common-good contribution, despite owning significant assets and receiving public and government income. These regulatory and accounting variations emanate from a state’s historically informed positional relationship with religion, which may be discordant against increasing religious pluralism and citizens’ commonly-held beliefs. To open a debate on state–church relationships within the accounting history literature, this article analyses changes in England since 1534. It utilises a state–church framework from Monsma and Soper, combined with an application and extension of Foucauldian governmentality. The longitudinal study shows direct and indirect governmentality tools change with the state–church relationship. Such harmonisation of regulatory approach relies on citizens/entities subverting imposition of state demands which fail to meet their concept of common-good