Physical activity levels in female rheumatoid arthritis patients on long term anti-TNF therapy compared to patients with active rheumatoid disease and healthy controls. [Abstract]

Background: Anti-TNF therapy has revolutionised the management of rheumatoid arthritis (RA) with rapid and sustained improvements in pain, function and quality of life. However, we do not know how this impacts upon habitual daily physical activity and whether treated patients attain activity levels seen in healthy controls. This study aimed to compare the physical activity levels of patients whose RA was well controlled on long-term anti-TNF therapy to RA patients with active arthritis and non-RA controls. Methods: Participants were patients on anti-TNF for more than two years (tRA) with DAS3.2 (aRA) and healthy controls (C), matched for age and BMI. Physical activity was assessed using the Actigraph GT3x+ accelerometer, worn throughout waking hours for seven days to determine time spent in light activity, moderate to vigorous physical activity (MVPA) and sedentary time. The International Physical Activity Questionnaire (IPAQ) was also completed. Groups were compared using analysis of variance with Bonferroni post hoc tests; Kruskal-Wallis or Mann-Whitney U- test as appropriate. Results: RA disease duration was significantly greater in tRA than aRA. Groups did not differ significantly in age, height, weight or body mass index (Table). Daily step count was significantly lower in aRA than tRA and C. Sedentary time (as a proportion of wear time) was significantly greater in aRA than tRA, whilst the reverse was true for light activity time. MVPA time was significantly lower in both RA groups than in controls. IPAQ questionnaires demonstrated significant differences between groups, with substantially higher values in C than RA groups in total METs and MET-minutes per week in domestic and garden, leisure, walking activities as well as total moderate and vigorous activities. RA patients had lower moderate to vigorous activity time than controls, regardless of treatment. aRA had lower light activity time, and more sedentary time, than tRA Conclusion: Moderate to vigorous physical activity should be promoted in all RA patients as even those with well controlled disease exhibit a deficit in comparison to control

Physical activity and sedentary behavior in women with rheumatoid arthritis: a comparison of patients with low and high disease activity and healthy controls

Objective: In rheumatoid arthritis (RA) patients, low levels of physical activity (PA) and high levels of sedentary behavior (SB) may play a role in enhancing cardiovascular risk. We do not know how long-term control of disease activity impacts upon daily PA levels and if treated patients attain PA levels seen in healthy controls. We therefore compared habitual levels of PA and SB between female RA patients with low disease activity achieved by anti-tumor necrosis factor (TNF) therapy, those with active arthritis (aRA) and non-RA controls. Methods: We carried out a cross-sectional comparison of 40 RA patients on anti-TNF therapy for >2 years with DAS28<3.2 (tRA), 32 patients on conventional disease modifying anti-rheumatic drugs with DAS28>3.2 (aRA) and 34 healthy controls (C) with the groups matched for age and body mass index. PA was assessed using the ActiGraph accelerometer to determine step count and time spent in moderate-to-vigorous physical activity (MVPA), light activity and sedentary time. Results: Daily step count was 72% higher in tRA and 40% higher in C in comparison to aRA (p<0.01). Sedentary time (as a proportion of wear time) was 10% less in tRA than aRA (p=0.03), while light activity time was 18% higher (p=0.014). Both RA groups had 40% lower MVPA time than C (p=0.001). Only half of either RA group fulfilled current WHO guidelines for PA compared with 82% of controls. Conclusion: RA patients who had long-term disease suppression were more physically active with less SB compared to RA patients with active disease. They had similar light PA and SB to controls although lower MVPA. Behavioral change interventions are likely to be needed in order to restore moderate exercise, further reduce SB and to meet guidelines for daily PA

Identification of a Human Monoclonal Antibody to Replace Equine Diphtheria Anti-toxin for the Treatment of Diphtheria

Diphtheria anti-toxin (DAT) has been used to treat Corynebacterium diphtheriae infection for over one hundred years. While the global incidence of diphtheria has declined in the 20th century, the disease remains endemic in many parts of the world and significant outbreaks still occur. Diphtheria anti-toxin is an equine polyclonal antibody with considerable side effects that is in critically short supply globally. A safer, more readily available alternative to DAT would be desirable. In the current study, we cloned human monoclonal antibodies (HuMabs) directly from antibody secreting cells of human volunteers immunized with Td vaccine. We isolated a diverse panel of HuMabs that recognized diphtheria toxoid and recombinant protein fragments of diphtheria toxin. Forty-one unique HuMabs were expressed in 293T cells and tested for neutralization of diphtheria toxin in in vitro cytotoxicity assays. The lead candidate HuMab, 315C4 potently neutralized diphtheria toxin with an EC50 of 0.65 ng/mL. Additionally, 25 μg of 315C4 completely protected guinea pigs in an in vivo lethality model. In comparison, 1.6 IU of DAT was necessary for full protection resulting in an estimated relative potency of 64 IU/mg for 315C4. We further established that our lead candidate HuMab binds to the receptor binding domain of diphtheria toxin and blocks the toxin from binding to the putative receptor, heparin binding-epidermal growth factor like growth factor. The discovery of a specific and potent neutralizing antibody against diphtheria toxin holds promise as a potential human therapeutic and is being developed for human use

Black hole thermodynamics with conical defects

Recently we have shown [1] how to formulate a thermodynamic first law for a single (charged) accelerated black hole in AdS space by fixing the conical deficit angles present in the spacetime. Here we show how to generalise this result, formulating thermodynamics for black holes with varying conical deficits. We derive a new potential for the varying tension defects: the thermodynamic length, both for accelerating and static black holes. We discuss possible physical processes in which the tension of a string ending on a black hole might vary, and also map out the thermodynamic phase space of accelerating black holes and explore their critical phenomena

The Regeneration Games: Commodities, Gifts and the Economics of London 2012

This paper considers contradictions between two concurrent and tacit conceptions of the Olympic ‘legacy’, setting out one conception that understands the games and their legacies as gifts alongside and as counterpoint to the prevailing discourse, which conceives Olympic assets as commodities. The paper critically examines press and governmental discussion of legacy, in order to locate these in the context of a wider perspective contrasting ‘gift’ and ‘commodity’ Olympics – setting anthropological conceptions of gift-based sociality as a necessary supplement to contractual and dis-embedded socioeconomic organizational assumptions underpinning the commodity Olympics. Costbenefit planning is central to modern city building and mega-event delivery. The paper considers the insufficiency of this approach as the exclusive paradigm within which to frame and manage a dynamic socio-economic and cultural legacy arising from the 2012 games

The intertwined geopolitics and geoeconomics of hopes/fears:China’s triple economic bubbles and the ‘One Belt One Road’ imaginary

This paper adopts a discursive-cum-material approach to China's new 'One Belt One Road' (OBOR) geostrategic imaginary and its development through the intertwining of geopolitics and geoeconomics of hopes and fears. It first contextualizes this development after the 2008 financial crisis when China promoted a vast stimulus package that inflated existing property and infrastructure bubbles and fuelled another in finance. Resulting debates over crisis management enabled an incoming President Xi to articulate a set of hope-based discourses that came to include 'China Dream', 'New Normal' and the OBOR. Familiar cartographic statecraft techniques and novel spatial metaphors were used to promote the OBOR's allegedly 'win-win' strategy discursively. The OBOR imaginary was translated materially, and importantly, into policies that promoted a grand transregional 'spatial fix' to postpone China's over-accumulation crises. This strategy is consolidating a China-oriented infrastructural mode of growth in production, finance and security. As this absorbs ever more productive and financial capital, we see the emergence of contradictions, antagonisms and conflicts, especially in the use of bilateral loan-debt contractuality to appropriate strategic infrastructure. The paper concludes with a call for an affective turn examining the intertwining of geoeconomics and geopolitics in the analysis of transregional spatial fixes

Pair creation of anti-de Sitter black holes on a cosmic string background

We analyze the quantum process in which a cosmic string breaks in an anti-de Sitter (AdS) background, and a pair of charged or neutral black holes is produced at the ends of the strings. The energy to materialize and accelerate the pair comes from the strings tension. In an AdS background this is the only study done in the process of production of a pair of correlated black holes with spherical topology. The acceleration $A$ of the produced black holes is necessarily greater than (|L|/3)^(1/2), where L<0 is the cosmological constant. Only in this case the virtual pair of black holes can overcome the attractive background AdS potential well and become real. The instantons that describe this process are constructed through the analytical continuation of the AdS C-metric. Then, we explicitly compute the pair creation rate of the process, and we verify that (as occurs with pair creation in other backgrounds) the pair production of nonextreme black holes is enhanced relative to the pair creation of extreme black holes by a factor of exp(Area/4), where Area is the black hole horizon area. We also conclude that the general behavior of the pair creation rate with the mass and acceleration of the black holes is similar in the AdS, flat and de Sitter cases, and our AdS results reduce to the ones of the flat case when L=0.Comment: 13 pages, 3 figures, ReVTeX

New AdS solitons and brane worlds with compact extra-dimensions

We construct new static, asymptotically AdS solutions where the conformal infinity is the product of Minkowski spacetime $M_n$ and a sphere $S^m$. Both globally regular, soliton-type solutions and black hole solutions are considered. The black holes can be viewed as natural AdS generalizations of the Schwarzschild black branes in Kaluza-Klein theory. The solitons provide new brane-world models with compact extra-dimensions. Different from the Randall-Sundrum single-brane scenario, a Schwarzschild black hole on the Ricci flat part of these branes does not lead to a naked singularity in the bulk.Comment: 28 pages, 4 figure

A systematic review of frameworks for the interrelationships of mental health evidence and policy in low- and middle-income countries

Background: The interrelationships between research evidence and policy-making are complex. Different theoretical frameworks exist to explain general evidence–policy interactions. One largely unexplored element of these interrelationships is how evidence interrelates with, and influences, policy/political agenda-setting. This review aims to identify the elements and processes of theories, frameworks and models on interrelationships of research evidence and health policy-making, with a focus on actionability and agenda-setting in the context of mental health in low- and middle-income countries (LMICs). Methods: A systematic review of theories was conducted based on the BeHeMOTh search method, using a tested and refined search strategy. Nine electronic databases and other relevant sources were searched for peer-reviewed and grey literature. Two reviewers screened the abstracts, reviewed full-text articles, extracted data and performed quality assessments. Analysis was based on a thematic analysis. The included papers had to present an actionable theoretical framework/model on evidence and policy interrelationships, such as knowledge translation or evidence-based policy, specifically target the agenda-setting process, focus on mental health, be from LMICs and published in English. Results: From 236 publications included in the full text analysis, no studies fully complied with our inclusion criteria. Widening the focus by leaving out ‘agenda-setting’, we included ten studies, four of which had unique conceptual frameworks focusing on mental health and LMICs but not agenda-setting. The four analysed frameworks confirmed research gaps from LMICs and mental health, and a lack of focus on agenda-setting. Frameworks and models from other health and policy areas provide interesting conceptual approaches and lessons with regards to agenda-setting. Conclusion: Our systematic review identified frameworks on evidence and policy interrelations that differ in their elements and processes. No framework fulfilled all inclusion criteria. Four actionable frameworks are applicable to mental health and LMICs, but none specifically target agenda-setting. We have identified agenda-setting as a research theory gap in the context of mental health knowledge translation in LMICs. Frameworks from other health/policy areas could offer lessons on agenda-setting and new approaches for creating policy impact for mental health and to tackle the translational gap in LMICs

The extremal limits of the C-metric: Nariai, Bertotti-Robinson and anti-Nariai C-metrics

In two previous papers we have analyzed the C-metric in a background with a cosmological constant, namely the de Sitter (dS) C-metric, and the anti-de Sitter (AdS) C-metric, following the work of Kinnersley and Walker for the flat C-metric. These exact solutions describe a pair of accelerated black holes in the flat or cosmological constant background, with the acceleration A being provided by a strut in-between that pushes away the two black holes. In this paper we analyze the extremal limits of the C-metric in a background with generic cosmological constant. We follow a procedure first introduced by Ginsparg and Perry in which the Nariai solution, a spacetime which is the direct topological product of the 2-dimensional dS and a 2-sphere, is generated from the four-dimensional dS-Schwarzschild solution by taking an appropriate limit, where the black hole event horizon approaches the cosmological horizon. Similarly, one can generate the Bertotti-Robinson metric from the Reissner-Nordstrom metric by taking the limit of the Cauchy horizon going into the event horizon of the black hole, as well as the anti-Nariai by taking an appropriate solution and limit. Using these methods we generate the C-metric counterparts of the Nariai, Bertotti-Robinson and anti-Nariai solutions, among others. One expects that the solutions found in this paper are unstable and decay into a slightly non-extreme black hole pair accelerated by a strut or by strings. Moreover, the Euclidean version of these solutions mediate the quantum process of black hole pair creation, that accompanies the decay of the dS and AdS spaces