The effects of shoe temperature on the kinetics and kinematics of running

The aim of the current investigation was to examine the effects of cooled footwear on the kinetics and kinematics of running in comparison to footwear at normal temperature. Twelve participants ran at 4.0 m/s ± 5% in both cooled and normal temperature footwear conditions over a force platform. Two identical footwear were worn, one of which was cooled for 30 min. Lower extremity kinematics were obtained using a motion capture system and tibial accelerations were measured using a triaxial accelerometer. Differences between cooled and normal footwear temperatures were contrasted using paired samples t-tests. The results showed that midsole temperature (cooled = 4.21 °C and normal = 23.25 °C) and maximal midsole deformation during stance (cooled = 12.85 mm and normal = 14.52 mm) were significantly reduced in the cooled footwear. In addition, instantaneous loading rate (cooled = 186.21 B.W/s and normal = 167.08 B W/s), peak tibial acceleration (cooled = 12.75 g and normal = 10.70 g) and tibial acceleration slope (cooled = 478.69 g/s and normal = 327.48 g/s) were significantly greater in the cooled footwear. Finally, peak eversion (cooled = −10.57 ° and normal = −7.83°) and tibial internal rotation (cooled = 10.67 ° and normal = 7.77°) were also shown to be significantly larger in the cooled footwear condition. This study indicates that running in cooled footwear may place runners at increased risk from the biomechanical parameters linked to the aetiology of injuries

HCMV Antivirals and Strategies to Target the Latent Reservoir.

Human cytomegalovirus (HCMV) is a ubiquitous human herpesvirus. In healthy people, primary infection is generally asymptomatic, and the virus can go on to establish lifelong latency in cells of the myeloid lineage. However, HCMV often causes severe disease in the immunosuppressed: transplant recipients and people living with AIDS, and also in the immunonaive foetus. At present, there are several antiviral drugs licensed to control HCMV disease. However, these are all faced with problems of poor bioavailability, toxicity and rapidly emerging viral resistance. Furthermore, none of them are capable of fully clearing the virus from the host, as they do not target latent infection. Consequently, reactivation from latency is a significant source of disease, and there remains an unmet need for treatments that also target latent infection. This review briefly summarises the most common HCMV antivirals used in clinic at present and discusses current research into targeting the latent HCMV reservoir

Bromodomain Inhibitors as Therapeutics for Herpesvirus-Related Disease: All BETs Are Off?

Although the ubiquitous human herpesviruses (HHVs) are rarely associated with serious disease of the healthy host, primary infection and reactivation in immunocompromised individuals can lead to significant morbidity and, in some cases, mortality. Effective drugs are available for clinical treatment, however resistance is on the rise such that new anti-viral targets, as well as novel clinical treatment strategies, are required. A promising area of development and pre-clinical research is that of inhibitors of epigenetic modifying proteins that control both cellular functions and the viral life cycle. Here, we briefly outline the interaction of the host bromo- and extra-terminal domain (BET) proteins during different stages of the HHVs' life cycles while giving a full overview of the published work using BET bromodomain inhibitors (BRDis) during HHV infections. Furthermore, we provide evidence that small molecule inhibitors targeting the host BET proteins, and BRD4 in particular, have the potential for therapeutic intervention of HHV-associated disease

The immunology of human cytomegalovirus latency: could latent infection be cleared by novel immunotherapeutic strategies?

While the host immune response following primary human cytomegalovirus (HCMV) infection is generally effective at stopping virus replication and dissemination, virus is never cleared by the host and like all herpesviruses, persists for life. At least in part, this persistence is known to be facilitated by the ability of HCMV to establish latency in myeloid cells in which infection is essentially silent with, importantly, a total lack of new virus production. However, although the viral transcription programme during latency is much suppressed, a number of viral genes are expressed during latent infection at the protein level and many of these have been shown to have profound effects on the latent cell and its environment. Intriguingly, many of these latency-associated genes are also expressed during lytic infection. Therefore, why the same potent host immune responses generated during lytic infection to these viral gene products are not recognized during latency, thereby allowing clearance of latently infected cells, is far from clear. Reactivation from latency is also a major cause of HCMV-mediated disease, particularly in the immune compromised and immune naive, and is also likely to be a major source of virus in chronic subclinical HCMV infection which has been suggested to be associated with long-term diseases such as atherosclerosis and some neoplasias. Consequently, understanding latency and why latently infected cells appear to be immunoprivileged is crucial for an understanding of the pathogenesis of HCMV and may help to design strategies to eliminate latent virus reservoirs, at least in certain clinical settings.This work was funded by British Medical Research Council Grant JS and MW - G0701279 and MR/K021087/1 and supported by the NIHR Cambridge BRC Cell Phenotyping hub.This is the accepted manuscript. The final version is available from the publisher at http://www.nature.com/cmi/journal/vaop/ncurrent/full/cmi201475a.html

Causality in Political Networks

As the study of political networks becomes more common in political science, greater attention to questions of causality is warranted. This essay explores competing visions of causality in political networks. Independent essays address issues of statistical model specification, identification of multi-step personal influence, measurement error, causality in historical perspective, and the insights of field experiments. These essays do not agree entirely on the nature of causality in political networks, though they commonly take seriously concerns regarding homophily, time- consistency, and the uniqueness of political network data. Serious consideration of these methodological issues promises to enhance the value-added of network analysis in the study of politics

Pathologies of Quenched Lattice QCD at non--zero Density and its Effective Potential

We simulate lattice QCD at non--zero baryon density and zero temperature in the quenched approximation, both in the scaling region and in the infinite coupling limit. We investigate the nature of the forbidden region -- the range of chemical potential where the simulations grow prohibitively expensive, and the results, when available, are puzzling if not unphysical. At weak coupling we have explored the sensitivity of these pathologies to the lattice size, and found that using a large lattice ($64 \times 16^3$) does not remove them. The effective potential sheds considerable light on the problems in the simulations, and gives a clear interpretation of the forbidden region. The strong coupling simulations were particularly illuminating on this point.Comment: 49 pages, uu-encoded expanding to postscript;also available at ftp://hlrz36.hlrz.kfa-juelich.de/pub/mpl/hlrz72_95.p