Despite maintaining a high daily training availability, a quarter of athletes start the season injured and three quarters experience injury in an Australian State Academy of Sport.

OBJECTIVES: To 1) investigate the incidence, prevalence, burden and characteristics of injuries; and 2) explore the frequency of physiotherapy and medical servicing for elite sports academy athletes over a 12-month season. DESIGN: Prospective cohort study. METHODS: Medical attention and time-loss injuries were prospectively recorded by Physiotherapy and Medical (Sports Physician) staff for 94 athletes (72.3% females). The number of linked physiotherapy and medical servicing appointments was also recorded. Injury incidence rates (IIR), point and period prevalence, and injury burden were calculated and compared by athlete gender, sport, and categorisation (performance level) using incidence rate ratios (IRR). RESULTS: The number of injuries reported was 193 in 71 (75.5%) athletes. The IIR was 2.1 (95%CI: 1.8 to 2.4) injuries per 365 days, with no gender difference observed (IRR: 1.1, 0.8 to 1.4). The injury burden was 43.5 (95%CI: 37.8 to 50.1) days absent per 365 days. More than one-quarter (point prevalence, 26.6%) of athletes commenced the season with an injury. In-season injury risk was 2.5 fold greater in athletes who started the season with an injury compared to athletes who started the season without an injury (IRR: 2.5, 1.9 to 3.4). The majority (81.2%) of the 1164 appointments recorded were physiotherapy, with an overall 4.3:1.0 physiotherapy to medical appointment ratio. CONCLUSIONS: One in four athletes began the elite pathway season with a pre-existing injury, while also demonstrating a 2.5 fold greater risk of subsequent injury in the scholarship period. Sports should not assume their athletes are uninjured at the beginning of their scholarship. Injury profiles, and physiotherapy and medical servicing varied across sports. To reduce health as a barrier in the successful transition of talented young athletes to elite athletes, injury management strategies at the commencement of recruitment and throughout the scholarship should be prioritised in the development pathway.

A Small-Molecule Inhibitor to the Cytokine Interleukin-4.

Interleukin-4 (IL-4) is a multifunctional cytokine and an important regulator of inflammation. When deregulated, IL-4 activity is associated with asthma, allergic inflammation, and multiple types of cancer. While antibody-based inhibitors targeting the soluble cytokine have been evaluated clinically, they failed to achieve their end points in trials. Small-molecule inhibitors are an attractive alternative, but identifying effective chemotypes that inhibit the protein-protein interactions between cytokines and their receptors remains an active area of research. As a result, no small-molecule inhibitors to the soluble IL-4 cytokine have yet been reported. Here, we describe the first IL-4 small-molecule inhibitor identified and characterized through a combination of binding-based approaches and cell-based activity assays. The compound features a nicotinonitrile scaffold with micromolar affinity and potency for the cytokine and disrupts type II IL-4 signaling in cells. Small-molecule inhibitors of these important cell-signaling proteins have implications for numerous immune-related disorders and inform future drug discovery and design efforts for these challenging protein targets.

Targeting Type 1 Diabetes: Selective Approaches for New Therapies.

The clinical onset of type 1 diabetes is characterized by the destruction of the insulin-producing ß cells of the pancreas and is caused by autoantigen-induced inflammation (insulitis) of the islets of Langerhans. The current standard of care for type 1 diabetes mellitus patients allows for management of the disease with exogenous insulin, but patients eventually succumb to many chronic complications such as limb amputation, blindness, and kidney failure. New therapeutic approaches now on the horizon are looking beyond glycemic management and are evaluating new strategies from protecting and regenerating endogenous islets to treating the underlying autoimmunity through selective modulation of key immune cell populations. Currently, there are no effective treatments for the autoimmunity that causes the disease, and strategies that aim to delay or prevent the onset of the disease will play an important role in the future of diabetes research. In this review, we summarize many of the key efforts underway that utilize molecular approaches to selectively modulate this disease and look at new therapeutic paradigms that can transform clinical treatment.

Sustained activation of ERK1/2 MAPK in Schwann cells causes corneal neurofibroma.

Recent studies have shown that constitutive activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in Schwann cells (SCs) increases myelin thickness in transgenic mice. In this secondary analysis, we report that these transgenic mice develop a postnatal corneal neurofibroma with the loss of corneal transparency by age six months. We show that expansion of non-myelinating SCs, under the control of activated ERK1/2, also drive myofibroblast differentiation that derives from both SC precursors and resident corneal keratocytes. Further, these mice also harbor activated mast cells in the central cornea, which contributes to pathological corneal neovascularization and fibrosis. This breach of corneal avascularity and immune status is associated with the growth of the tumor pannus, resulting in a corneal stroma that is nearly four times its normal size. In corneas with advanced disease, some axons became ectopically myelinated, and the disruption of Remak bundles is evident. To determine whether myofibroblast differentiation was linked to vimentin, we examined the levels and phosphorylation status of this fibrotic biomarker. Concomitant with the early upregulation of vimentin, a serine 38-phosphorylated isoform of vimentin (pSer38vim) increased in SCs, which was attributed primarily to the soluble fraction of protein-not the cytoskeletal portion. However, the overexpressed pSer38vim became predominantly cytoskeletal with the growth of the corneal tumor. Our findings demonstrate an unrecognized function of ERK1/2 in the maintenance of corneal homeostasis, wherein its over-activation in SCs promotes corneal neurofibromas. This study is also the first report of a genetically engineered mouse that spontaneously develops a corneal tumor.

Quantum critical scaling in graphene.

We show that the emergent relativistic symmetry of electrons in graphene near its quantum critical point (QCP) implies a crucial importance of the Coulomb interaction. We derive scaling laws, valid near the QCP, that dictate the nontrivial magnetic and charge response of interacting graphene. Our analysis yields numerous predictions for how the Coulomb interaction will be manifested in experimental observables such as the diamagnetic response and electronic compressibility.

BEC-BCS crossover in "magnetized" Feshbach-resonantly paired superfluids.

We map out the detuning-magnetization phase diagram for a magnetized (unequal number of atoms in two pairing hyperfine states) gas of fermionic atoms interacting via an s-wave Feshbach resonance (FR). The phase diagram is dominated by the coexistence of a magnetized normal gas and a singlet-paired superfluid with the latter exhibiting a BCS-Bose Einstein condensate crossover with reduced FR detuning. On the BCS side of strongly overlapping Cooper pairs, a sliver of finite-momentum paired Fulde-Ferrell-Larkin-Ovchinnikov magnetized phase intervenes between the phase-separated and normal states. In contrast, for large negative detuning a uniform, polarized superfluid, that is, a coherent mixture of singlet Bose-Einstein-condensed molecules and fully magnetized single-species Fermi sea, is a stable ground state.

Superfluid transition in a rotating fermi gas with resonant interactions.

We study a rotating atomic Fermi gas near a narrow s-wave Feshbach resonance in a uniaxial trap with frequencies Omega perpendicular, Omega z. We predict the upper-critical angular velocity, omega c2(delta,T), as a function of temperature T and detuning delta across the BEC-BCS crossover. The suppression of superfluidity at omega c2 is distinct in the BCS and BEC regimes, with the former controlled by depairing and the latter by the dilution of bosonic molecules. At low T and Omega z << Omega perpendicular, in the BCS and crossover regimes of 0 less similar delta less similar delta c, omega c2 is implicitly given by [formula: see text], vanishing as omega c2 approximately Omega perpendicular(1 - delta/delta c)(1/2) near [formula: see text] (with Delta the BCS gap and gamma the resonance width), and extending the bulk result variant Planck's over 2pi omega c2 approximately 2Delta2/epsilonF to a trap. In the BEC regime of delta < 0 we find omega c2-->Omega perpendicular-, where molecular superfluidity is destroyed only by large quantum fluctuations associated with comparable boson and vortex densities.

Quantum decoupling transition in a one-dimensional Feshbach-resonant superfluid.

We study a one-dimensional gas of fermionic atoms interacting via an s-wave molecular Feshbach resonance. At low energies the system is characterized by two Josephson-coupled Luttinger liquids, corresponding to paired atomic and molecular superfluids. We show that, in contrast to higher dimensions, the system exhibits a quantum phase transition from a phase in which the two superfluids are locked together to one in which, at low energies, quantum fluctuations suppress the Feshbach resonance (Josephson) coupling, effectively decoupling the molecular and atomic superfluids. Experimental signatures of this quantum transition include the appearance of an out-of-phase gapless mode (in addition to the standard gapless in-phase mode) in the spectrum of the decoupled superfluid phase and a discontinuous change in the molecular momentum distribution function.