Limbal stem cell deficiency (LSCD) is a disease resulting from the loss or dysfunction of epithelial stem cells, which seriously impairs sight. Autologous limbal stem cell transplantation is ...effective in unilateral or partial bilateral disease but not applicable in total bilateral disease. An allogeneic source of transplantable cells for use in total bilateral disease can be obtained from culture of donated cadaveric corneal tissue. We performed a controlled multicenter study to examine the feasibility, safety, and efficacy of allogeneic corneal epithelial stem cells in the treatment of bilateral LSCD. Patients were randomized to receive corneal epithelial stem cells cultured on amniotic membrane (AM): investigational medicinal product (IMP) or control AM only. Patients received systemic immunosuppression. Primary endpoints were safety and visual acuity, secondary endpoint was change in composite ocular surface score (OSS). Sixteen patients were treated and 13 patients completed all assessments. Safety was demonstrated and 9/13 patients had improved visual acuity scores at the end of the trial, with no significant differences between IMP and control groups. Patients in the IMP arm demonstrated significant, sustained improvement in OSS, whereas those in the control arm did not. Serum cytokine levels were measured during and after the period of immune suppression and we identified strongly elevated levels of CXCL8 in the serum of patients with aniridia, which persisted throughout the trial. This first randomized control trial of allogeneic corneal epithelial stem cells in severe bilateral LSCD demonstrates the feasibility and safety of this approach. Stem Cells Translational Medicine 2019;8:323–331
Patients with severe ocular surface disorder received transplants of amniotic membrane with (black bars) or without (gray bars) cadaveric‐donor‐derived cultured limbal stem cells. All patients received immune suppression. Only patients who received transplants containing limbal stem cells showed sustained significant improvements (reductions) in combined ocular surface scores (5 factors scored 0–3 where 0 is a normal eye score).
While group VII 4d Tc and 5d Re have hexagonally close-packed (hcp) ground states, 3d Mn adopts the complex chi-phase which exhibits non-collinear magnetism. Density functional theory (DFT) ...calculations have shown that without magnetism the chi-phase remains the ground state of Mn implying that magnetism is not the critical factor, as is commonly believed, in driving the anomalous stability of the chi-phase over hcp. Using a tight-binding (TB) model it is found that while harder potentials stabilise close-packed hcp, a softer potential stabilises the more open chi-phase. By analogy with the structural trend from open to close-packed phases down the group IV elements, the anomalous stability of the chi-phase in Mn is shown to be due to 3d valent Mn lacking d states in the core which leads to an effectively softer atomic repulsion between the atoms than in 4d Tc and 5d Re. Subsequently an analytic Bond-Order Potential (BOP) is developed to investigate the structural and magnetic properties of elemental Mn at 0 K. It is derived within BOP theory directly from a new short-ranged orthogonal d-valent TB model of Mn, the parameters of which are fitted to reproduce the DFT binding energy curves of the five experimentally observed phases of Mn, alpha, beta, gamma, delta, and epsilon-Mn. Not only does the BOP reproduce qualitatively DFT binding energy curves of the five different structure types, it also predicts the complex collinear antiferromagnetic (AFM) ordering in alpha-Mn, the ferrimagnetic (FiM) ordering in beta-Mn and the AFM ordering in the other phases that are found by DFT. A BOP expansion including 14 moments is sufficiently converged to reproduce most of the properties of the TB model with the exception of the elastic shear constants which require further moments. Magnetic analytic BOPs are also developed for Fe and Fe-Mn. The Fe model correctly reproduces trends in the structural stabilities of the common metallic structures except that AFM hcp is overstabilised. Reproduction of the elastic constants with a 9-moment BOP is reasonable although as is found for the Mn BOP the elastic shear constants require more moments to converge. Vacancy formation energies are close to those determined by experiment and DFT and the relative stabilities of self-interstitial atom (SIA) defects in ferromagnetic bcc Fe are correctly reproduced. The SIA formation energies are found to be better than those calculated with existing BOP models. The Fe-Mn TB and BOP models were challenging to fit and nonmagnetic face-centred cubic (fcc) structures are overstabilised. Furthermore within BOP an incorrect magnetic solution is predicted for one fcc structure resulting in poor reproduction of the DFT stacking fault energies. Refitting the bond integrals might help to better reproduce the nonmagnetic hcp-fcc energy differences while an environment-dependent Stoner parameter could help provide the flexibility needed to correctly capture the magnetic energy differences.
While group VII 4d Tc and 5d Re have hexagonally close-packed (hcp) ground states, 3d Mn adopts the complex chi-phase which exhibits non-collinear magnetism. Density functional theory (DFT) ...calculations have shown that without magnetism the chi-phase remains the ground state of Mn implying that magnetism is not the critical factor, as is commonly believed, in driving the anomalous stability of the chi-phase over hcp. Using a tight-binding (TB) model it is found that while harder potentials stabilise close-packed hcp, a softer potential stabilises the more open chi-phase. By analogy with the structural trend from open to close-packed phases down the group IV elements, the anomalous stability of the chi-phase in Mn is shown to be due to 3d valent Mn lacking d states in the core which leads to an effectively softer atomic repulsion between the atoms than in 4d Tc and 5d Re. Subsequently an analytic Bond-Order Potential (BOP) is developed to investigate the structural and magnetic properties of elemental Mn at 0 K. It is derived within BOP theory directly from a new short-ranged orthogonal d-valent TB model of Mn, the parameters of which are fitted to reproduce the DFT binding energy curves of the five experimentally observed phases of Mn, alpha, beta, gamma, delta, and epsilon-Mn. Not only does the BOP reproduce qualitatively DFT binding energy curves of the five different structure types, it also predicts the complex collinear antiferromagnetic (AFM) ordering in alpha-Mn, the ferrimagnetic (FiM) ordering in beta-Mn and the AFM ordering in the other phases that are found by DFT. A BOP expansion including 14 moments is sufficiently converged to reproduce most of the properties of the TB model with the exception of the elastic shear constants which require further moments. Magnetic analytic BOPs are also developed for Fe and Fe-Mn. The Fe model correctly reproduces trends in the structural stabilities of the common metallic structures except that AFM hcp is overstabilised. Reproduction of the elastic constants with a 9-moment BOP is reasonable although as is found for the Mn BOP the elastic shear constants require more moments to converge. Vacancy formation energies are close to those determined by experiment and DFT and the relative stabilities of self-interstitial atom (SIA) defects in ferromagnetic bcc Fe are correctly reproduced. The SIA formation energies are found to be better than those calculated with existing BOP models. The Fe-Mn TB and BOP models were challenging to fit and nonmagnetic face-centred cubic (fcc) structures are overstabilised. Furthermore within BOP an incorrect magnetic solution is predicted for one fcc structure resulting in poor reproduction of the DFT stacking fault energies. Refitting the bond integrals might help to better reproduce the nonmagnetic hcp-fcc energy differences while an environment-dependent Stoner parameter could help provide the flexibility needed to correctly capture the magnetic energy differences.
This article details the experience of Tissue Services staff establishing a bone harvesting programme to augment the existing bone supplies in the North of Scotland. It demonstrates that there is a ...demand for a steady supply of safe, economical bone allograft.
Gold nanoparticles have unique properties that are highly dependent on their shape and size. Synthetic methods that enable precise control over nanoparticle morphology currently require ...shape‐directing agents such as surfactants or polymers that force growth in a particular direction by adsorbing to specific crystal facets. These auxiliary reagents passivate the nanoparticles' surface, and thus decrease their performance in applications like catalysis and surface‐enhanced Raman scattering. Here, a surfactant‐ and polymer‐free approach to achieving high‐performance gold nanoparticles is reported. A theoretical framework to elucidate the growth mechanism of nanoparticles in surfactant‐free media is developed and it is applied to identify strategies for shape‐controlled syntheses. Using the results of the analyses, a simple, green‐chemistry synthesis of the four most commonly used morphologies: nanostars, nanospheres, nanorods, and nanoplates is designed. The nanoparticles synthesized by this method outperform analogous particles with surfactant and polymer coatings in both catalysis and surface‐enhanced Raman scattering.
A new theoretical framework that identifies a surfactant‐free route to control the shape of nanoparticles is presented. For the first time, it is predicted and confirmed that gold nanorod formation in the absence of surfactants is driven by re‐entrant groove defects on the end facets. Nanoparticles synthesized by this approach demonstrate excellent surface‐enhanced Raman scattering and catalytic performance.
ABSTRACT
Introduction
The injury definitions and surveillance methods commonly used in Army basic military training (BMT) research may underestimate the extent of injury. This study therefore aims to ...obtain a comprehensive understanding of injuries sustained during BMT by employing recording methods to capture all physical complaints.
Materials and methods
Six hundred and forty-six recruits were assessed over the 12-week Australian Army BMT course. Throughout BMT injury, data were recorded via (1) physiotherapy reports following recruit consultation, (2) a member of the research team (third party) present at physical training sessions, and (3) recruit daily self-reports.
Results
Two hundred and thirty-five recruits had ≥1 incident injury recorded by physiotherapists, 365 recruits had ≥1 incident injury recorded by the third party, and 542 recruits reported ≥1 injury-related problems via the self-reported health questionnaire. Six hundred twenty-one, six hundred eighty-seven, and two thousand nine hundred sixty-four incident injuries were recorded from a total of 997 physiotherapy reports, 1,937 third-party reports, and 13,181 self-reported injury-related problems, respectively. The lower extremity was the most commonly injured general body region as indicated by all three recording methods. Overuse accounted for 79% and 76% of documented incident injuries from physiotherapists and the third party, respectively.
Conclusions
This study highlights that injury recording methods impact injury reporting during BMT. The present findings suggest that traditional injury surveillance methods, which rely on medical encounters, underestimate the injury profile during BMT. Considering accurate injury surveillance is fundamental in the sequence of injury prevention, implementing additional injury recording methods during BMT may thus improve injury surveillance and better inform training modifications and injury prevention programs.
To determine the effect of a novel low volume high intensity concurrent training regimen and warm-up on physiological performance and musculoskeletal injury in Australian recruits.
Controlled ...longitudinal intervention.
Military recruits completed 12 weeks of either experimental (EXP: n=78, 6-8RM resistance loads, and high intensity intervals) or basic military (CON: n=69, usual practice) matched for total sessions and time. Endurance (3.2km 22kg-load carriage, V˙O2 peak, multi-stage fitness test (MSFT)), 1RM strength and local muscle endurance (bench, squat, box-lift and push-ups) and power (squat jump) were assessed at Weeks 1,6,12. Body composition, physical activity (PAC·min−1) and heart rate reserve (HRR%), were assessed at Weeks 2,7,9. Musculoskeletal injury and mechanism were recorded. Two-way repeated measures ANOVA interaction (group×time), mean difference and effect size (ES) are reported p≤0.05.
A significant interaction over 12 weeks was observed for load carriage (ES −0.30), squat jump (ES 0.65), V˙O2 peak (ES 0.58), MSFT (ES 0.41), push-ups (ES 0.26), 1RM bench (ES 0.26), squat (ES 1.05) and box lift (ES 0.27) in EXP compared to CON. At Week 12 significantly greater squat (38.9kg), MSFT (2.1mL·kg−1·min−1), and faster load carriage (49.9s) was observed in EXP than CON, but no difference in body composition. EXP had a lower PAC·min−1 (641.1±63.1) but higher HRR% (21.8±4.0) compared to CON. EXP had a lower number of injuries (6) compared to CON (17).
The inclusion of compound-specific resistance exercise and high intensity intervals improved physical function and was associated with reduced musculoskeletal injury.
ABSTRACT
Introduction
Subjective measures may offer practitioners a relatively simple method to monitor recruit responses to basic military training (BMT). Yet, a lack of agreement between subjective ...and objective measures may presents a problem to practitioners wishing to implement subjective monitoring strategies. This study therefore aims to examine associations between subjective and objective measures of workload and sleep in Australian Army recruits.
Materials and Methods
Thirty recruits provided daily rating of perceived exertion (RPE) and differential RPE (d-RPE) for breathlessness and leg muscle exertion each evening. Daily internal workloads determined via heart rate monitors were expressed as Edwards training impulse (TRIMP) and average heart rate. External workloads were determined via global positioning system (PlayerLoadTM) and activity monitors (step count). Subjective sleep quality and duration was monitored in 29 different recruits via a customized questionnaire. Activity monitors assessed objective sleep measures. Linear mixed-models assessed associations between objective and subjective measures. Akaike Information Criterion assessed if the inclusion of d-RPE measures resulted in a more parsimonious model. Mean bias, typical error of the estimate (TEE) and within-subject repeated measures correlations examined agreement between subjective and objective sleep duration.
Results
Conditional R2 for associations between objective and subjective workloads ranged from 0.18 to 0.78, P < 0.01, with strong associations between subjective measures of workload and TRIMP (0.65–0.78), average heart rate (0.57–0.73), and PlayerLoadTM (0.54–0.68). Including d-RPE lowered Akaike Information Criterion. The slope estimate between objective and subjective measures of sleep quality was not significant. A trivial relationship (r = 0.12; CI −0.03, 0.27) was observed between objective and subjective sleep duration with subjective measures overestimating (mean bias 25 min) sleep duration (TEE 41 min).
Conclusions
Daily RPE offers a proxy measure of internal workload in Australian Army recruits; however, the current subjective sleep questionnaire should not be considered a proxy measure of objective sleep measures.
To investigate the heterogeneity of physical adaptation in Australian Army recruits completing a 12-week basic military training regimen.
A prospective research design.
Volunteer recruits (n=195) ...completed 12-weeks of basic military training. Recruit physical fitness was assessed at week 1, weeks 6–8 and week 12. Recruits in the upper (75th) and lower (25th) quartiles for each assessment were then analysed using a repeated measures two-way ANOVA. The relative magnitude of recruit adaptions were classified as positive response (Rpositive, ≥5%), limited response (Rlimited, >−5% to <5%) and negative response (Rnegative, ≤−5%); Chi-square analysis determined the proportional differences in the distribution of each quartile.
An interaction (p<0.001) was observed in the lower and upper recruit quartiles for all assessments of physical fitness at each time point. After 12 weeks of military training the mean difference of the highest quartile was; 20-m multi-stage fitness test 7.4mL·kg−1·min−1, (CI:5.8:9.1), 2-min push-ups 20.1 reps, (CI:16.2:23.9), 1RM box lift 5.6kg, (CI:2.6:5.8) and load carriage 222.1s, (CI:174.7:269.4) compared to the lowest recruit quartile. The highest quartile demonstrated no improvement in 1RM box lift (−4%, −1%) and push-ups (2%, 0%) performance at weeks 6–8 and week 12 respectively. In contrast, adaptations in the lowest quartile for 1RM box lift (16%, 21%) and push-ups (46%, 46%) over the same time periods were observed.
A significant proportion of recruits may complete basic military training with a decline in physical performance. Higher relative-intensity cardiorespiratory and resistance exercise should be considered to facilitate physical adaptation in all recruits.