Effect of accelerated rehabilitation on function after ankle sprain: randomised controlled trial

Objective: To compare an accelerated intervention incorporating early therapeutic exercise after acute ankle sprains with a standard protection, rest, ice, compression, and elevation intervention.

Design: Randomised controlled trial with blinded outcome assessor.

Setting: Accident and emergency department and university based sports injury clinic.

Participants: 101 patients with an acute grade 1 or 2 ankle sprain.

Interventions: Participants were randomised to an accelerated intervention with early therapeutic exercise (exercise group) or a standard protection, rest, ice, compression, and elevation intervention (standard group).

Main outcome measures: The primary outcome was subjective ankle function (lower extremity functional scale). Secondary outcomes were pain at rest and on activity, swelling, and physical activity at baseline and at one, two, three, and four weeks after injury. Ankle function and rate of reinjury were assessed at 16 weeks.

Results: An overall treatment effect was in favour of the exercise group (P=0.0077); this was significant at both week 1 (baseline adjusted difference in treatment 5.28, 98.75% confidence interval 0.31 to 10.26; P=0.008) and week 2 (4.92, 0.27 to 9.57; P=0.0083). Activity level was significantly higher in the exercise group as measured by time spent walking (1.2 hours, 95% confidence interval 0.9 to 1.4 v 1.6, 1.3 to 1.9), step count (5621 steps, 95% confidence interval 4399 to 6843 v 7886, 6357 to 9416), and time spent in light intensity activity (53 minutes, 95% confidence interval 44 to 60 v 76, 58 to 95). The groups did not differ at any other time point for pain at rest, pain on activity, or swelling. The reinjury rate was 4% (two in each group).

Conclusion: An accelerated exercise protocol during the first week after ankle sprain improved ankle function; the group receiving this intervention was more active during that week than the group receiving standard care.

Dependence of laser accelerated protons on laser energy following the interaction of defocused, intense laser pulses with ultra-thin targets

The scaling of the flux and maximum energy of laser-driven sheath-accelerated protons has been investigated as a function of laser pulse energy in the range of 15-380 mJ at intensities of 10(16)-10(18) W/cm(2). The pulse duration and target thickness were fixed at 40 fs and 25 nm, respectively, while the laser focal spot size and drive energy were varied. Our results indicate that while the maximum proton energy is dependent on the laser energy and laser spot diameter, the proton flux is primarily related to the laser pulse energy under the conditions studied here. Our measurements show that increasing the laser energy by an order of magnitude results in a more than 500-fold increase in the observed proton flux. Whereas, an order of magnitude increase in the laser intensity generated by decreasing the laser focal spot size, at constant laser energy, gives rise to less than a tenfold increase in observed proton flux.

Spectral modification of laser-accelerated proton beams by self-generated magnetic fields

Target normal measurements of proton energy spectra from ultrathin (50-200 nm) planar foil targets irradiated by 10(19) W cm(-2) 40 fs laser pulses exhibit broad maxima that are not present in the energy spectra from micron thickness targets (6 mu m). The proton flux in the peak is considerably greater than the proton flux observed in the same energy range in thicker targets. Numerical modelling of the experiment indicates that this spectral modification in thin targets is caused by magnetic fields that grow at the rear of the target during the laser-target interaction.

Dynamic control and enhancement of laser-accelerated protons using multiple laser pulses

The use of schemes involving multiple laser pulses to enhance and control the properties of beams of protons accelerated in ultra-intense laser irradiation of planar foil targets is discussed. Specifically, the schemes include the use of a second laser pulse to produce and control preplasma expansion of the target to enhance energy coupling to the proton beam; the use of a second laser pulse to drive shock deformation of the target to change the direction of the proton beam; and a scheme involving dual high intensity laser pulses to change the properties of the sheath field, with the aim of modifying the proton energy spectrum. An overview of our recent experimental and theoretical results is given. The overall aim of this work is to determine the extent to which the properties of the sheath-accelerated proton beam can be optically controlled, to enable beam delivery at high repetition rates. To cite this article: D.C. Carroll et al., C. R. Physique 10 (2009). (C) 2009 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.

Active manipulation of the spatial energy distribution of laser-accelerated proton beams

The spatial energy distributions of beams of protons accelerated by ultrahigh intensity (> 10(19) W/cm(2)) picosecond laser pulse interactions with thin foil targets are investigated. Using separate, low intensity (

Employing Laser-Accelerated Proton Beams to Diagnose High Intensity Laser-Plasma Interactions

A review of the proton radiography technique will be presented. This technique employs laser-accelerated laminar bunches of protons to diagnose the temporal and spatial characteristic of the electric and magnetic fields generated during high-intensity laser-plasma interactions. The remarkable temporal and spatial resolution that this technique can achieve (of the order of a picosecond and a few microns respectively) candidates this technique as the preferrable one, if compared to other techniques, to probe high intensity laser-matterinteractions.

Radiochromic film imaging spectroscopy of laser-accelerated proton beams

This article reports on an experimental method to fully reconstruct laser-accelerated proton beam parameters called radiochromic film imaging spectroscopy (RIS). RIS allows for the characterization of proton beams concerning real and virtual source size, envelope- and microdivergence, normalized transverse emittance, phase space, and proton spectrum. This technique requires particular targets and a high resolution proton detector. Therefore thin gold foils with a microgrooved rear side were manufactured and characterized. Calibrated GafChromic radiochromic film (RCF) types MD-55, HS, and HD-810 in stack configuration were used as spatial and energy resolved film detectors. The principle of the RCF imaging spectroscopy was demonstrated at four different laser systems. This can be a method to characterize a laser system with respect to its proton-acceleration capability. In addition, an algorithm to calculate the spatial and energy resolved proton distribution has been developed and tested to get a better idea of laser-accelerated proton beams and their energy deposition with respect to further applications.

Radiochromic film spectroscopy of laser-accelerated proton beams using the FLUKA code and dosimetry traceable to primary standards

A new approach to spectroscopy of laser induced proton beams using radiochromic film (RCF) is presented. This approach allows primary standards of absorbed dose-to-water as used in radiotherapy to be transferred to the calibration of GafChromic HD-810 and EBT in a 29 MeV proton beam from the Birmingham cyclotron. These films were then irradiated in a common stack configuration using the TARANIS Nd:Glass multi-terawatt laser at Queens University Belfast, which can accelerate protons to 10-12 MeV, and a depth-dose curve was measured from a collimated beam. Previous work characterizing the relative effectiveness (RE) of GafChromic film as a function of energy was implemented into Monte Carlo depth-dose curves using FLUKA. A Bragg peak (BP) "library" for proton energies 0-15 MeV was generated, both with and without the RE function. These depth-response curves were iteratively summed in a FORTRAN routine to solve for the measured RCF depth-dose using a simple direct search algorithm. By comparing resultant spectra with both BP libraries, it was found that the effect of including the RE function accounted for an increase in the total number of protons by about 50%. To account for the energy loss due to a 20 mu m aluminum filter in front of the film stack, FLUKA was used to create a matrix containing the energy loss transformations for each individual energy bin. Multiplication by the pseudo-inverse of this matrix resulted in "up-shifting" protons to higher energies. Applying this correction to two laser shots gave further increases in the total number of protons, N of 31% and 56%. Failure to consider the relative response of RCF to lower proton energies and neglecting energy losses in a stack filter foil can potentially lead to significant underestimates of the total number of protons in RCF spectroscopy of the low energy protons produced by laser ablation of thin targets.

Rayleigh-Taylor Instability of an Ultrathin Foil Accelerated by the Radiation Pressure of an Intense Laser

We report experimental evidence for a Rayleigh-Taylor-like instability driven by radiation pressure of an ultraintense (1021W/cm2) laser pulse. The instability is witnessed by the highly modulated profile of the accelerated proton beam produced when the laser irradiates a 5 nm diamondlike carbon (90% C, 10% H) target. Clear anticorrelation between bubblelike modulations of the proton beam and transmitted laser profile further demonstrate the role of the radiation pressure in modulating the foil. Measurements of the modulation wavelength, and of the acceleration from Doppler-broadening of back-reflected light, agree quantitatively with particle-in-cell simulations performed for our experimental parameters and which confirm the existence of this instability. © 2012 American Physical Society.

Simulations of Biased Agonists in the β2 Adrenergic Receptor with Accelerated Molecular Dynamics

The biased agonism of the G protein-coupled receptors (GPCRs), where in addition to a traditional G protein-signalling pathway a GPCR promotes intracellular signals though ß-arrestin, is a novel paradigm in pharmacology. Biochemical and biophysical studies have suggested that a GPCR forms a distinct ensemble of conformations signalling through the G protein and ß-arrestin. Here we report on the dynamics of the ß2 adrenergic receptor bound to the ß-arrestin and G protein biased agonists and the empty receptor to further characterize the receptor conformational changes caused by biased agonists. We use conventional and accelerated molecular dynamics (aMD) simulations to explore the conformational transitions of the GPCR from the active state to the inactive state. We found that aMD simulations enable monitoring the transition within the nanosecond timescale while capturing the known microscopic characteristics of the inactive states, such as the ionic lock, the inward position of F6.44, and water clusters. Distinct conformational states are shown to be stabilized by each biased agonist. In particular, in simulations of the receptor with the ß-arrestin biased agonist, N-cyclopentylbutanepherine we observe a different pattern of motions in helix 7 when compared to simulations with the G protein biased agonist, Salbutamol that involves perturbations of the network of interactions within the NPxxY motif. Understanding the network of interactions induced by biased ligands and the subsequent receptor conformational shifts will lead to development of more efficient drugs. © 2013 American Chemical Society

Age-dependent increase in ortho-tyrosine and methionine sulfoxide in human skin collagen is not accelerated in diabetes. Evidence against a generalized increase in oxidative stress in diabetes

The glycoxidation products Nepsilon-(carboxymethyl)lysine and pentosidine increase in skin collagen with age and at an accelerated rate in diabetes. Their age-adjusted concentrations in skin collagen are correlated with the severity of diabetic complications. To determine the relative roles of increased glycation and/or oxidation in the accelerated formation of glycoxidation products in diabetes, we measured levels of amino acid oxidation products, distinct from glycoxidative modifications of amino acids, as independent indicators of oxidative stress and damage to collagen in aging and diabetes. We show that ortho-tyrosine and methionine sulfoxide are formed in concert with Nepsilon-(carboxymethyl)lysine and pentosidine during glycoxidation of collagen in vitro, and that they also increase with age in human skin collagen. The age-adjusted levels of these oxidized amino acids in collagen was the same in diabetic and nondiabetic subjects, arguing that diabetes per se does not cause an increase in oxidative stress or damage to extracellular matrix proteins. These results provide evidence for an age-dependent increase in oxidative damage to collagen and support previous conclusions that the increase in glycoxidation products in skin collagen in diabetes can be explained by the increase in glycemia alone, without invoking a generalized, diabetes-dependent increase in oxidative stress.