ABSTRACT
Inverted perovskite solar cells (PSCs) promise enhanced operating stability compared to their normal-structure counterparts1-3. To improve efficiency further, it is crucial to combine effective light management with low interfacial losses4,5. Here we develop a conformal self-assembled monolayer (SAM) as the hole-selective contact on light-managing textured substrates. Molecular dynamics simulations indicate that cluster formation during phosphonic acid adsorption leads to incomplete SAM coverage. We devise a co-adsorbent strategy that disassembles high-order clusters, thus homogenizing the distribution of phosphonic acid molecules, and thereby minimizing interfacial recombination and improving electronic structures. We report a laboratory-measured power conversion efficiency (PCE) of 25.3% and a certified quasi-steady-state PCE of 24.8% for inverted PSCs, with a photocurrent approaching 95% of the Shockley-Queisser maximum. An encapsulated device having a PCE of 24.6% at room temperature retains 95% of its peak performance when stressed at 65 °C and 50% relative humidity following more than 1,000 h of maximum power point tracking under 1 sun illumination. This represents one of the most stable PSCs subjected to accelerated ageing: achieved with a PCE surpassing 24%. The engineering of phosphonic acid adsorption on textured substrates offers a promising avenue for efficient and stable PSCs. It is also anticipated to benefit other optoelectronic devices that require light management.
ABSTRACT
All-perovskite tandem solar cells hold the promise of surpassing the efficiency limits of single-junction solar cells1-3; however, until now, the best-performing all-perovskite tandem solar cells have exhibited lower certified efficiency than have single-junction perovskite solar cells4,5. A thick mixed Pb-Sn narrow-bandgap subcell is needed to achieve high photocurrent density in tandem solar cells6, yet this is challenging owing to the short carrier diffusion length within Pb-Sn perovskites. Here we develop ammonium-cation-passivated Pb-Sn perovskites with long diffusion lengths, enabling subcells that have an absorber thickness of approximately 1.2 µm. Molecular dynamics simulations indicate that widely used phenethylammonium cations are only partially adsorbed on the surface defective sites at perovskite crystallization temperatures. The passivator adsorption is predicted to be enhanced using 4-trifluoromethyl-phenylammonium (CF3-PA), which exhibits a stronger perovskite surface-passivator interaction than does phenethylammonium. By adding a small amount of CF3-PA into the precursor solution, we increase the carrier diffusion length within Pb-Sn perovskites twofold, to over 5 µm, and increase the efficiency of Pb-Sn perovskite solar cells to over 22%. We report a certified efficiency of 26.4% in all-perovskite tandem solar cells, which exceeds that of the best-performing single-junction perovskite solar cells. Encapsulated tandem devices retain more than 90% of their initial performance after 600 h of operation at the maximum power point under 1 Sun illumination in ambient conditions.
ABSTRACT
Transparent conductors (TCs) play a vital role in displays, solar cells, and emerging printed electronics. Here, we report a solution-processable n-doped organic conductor from copper-catalyzed cascade reactions in the air, which involves oxidative polymerization and reductive doping in one pot. The formed polymer ink is shelf-stable over 20 days and can endure storage temperatures from -20 to 65 °C. The optimized n-doped thin-film TC exhibits a low sheet resistance of 45 Ω/sq and a high transmittance (T550 > 80%), which can rival indium tin oxide. The transparent organic conductor exhibits excellent durability under accelerated weathering tests (85 °C/85% RH). Furthermore, the n-doped polymer film can also function as an electrode material with a high volumetric capacity. When it is paired with p-doped PEDOT:PSS, a record-high coloration efficiency is obtained in a dual-polymer electrochromic device.
ABSTRACT
The development of metal halide perovskite/perovskite heterostructures is hindered by rapid interfacial halide diffusion leading to mixed alloys rather than sharp interfaces. To circumvent this outcome, we developed an ion-blocking layer consisting of single-layer graphene (SLG) deposited between the metal halide perovskite layers and demonstrated that it effectively blocks anion diffusion in a CsPbBr3/SLG/CsPbI3 heterostructure. Spatially resolved elemental analysis and spectroscopic measurements demonstrate the halides do not diffuse across the interface, whereas control samples without the SLG show rapid homogenization of the halides and loss of the sharp interface. Ultraviolet photoelectron spectroscopy, DFT calculations, and transient absorbance spectroscopy indicate the SLG has little electronic impact on the individual semiconductors. In the CsPbBr3/SLG/CsPbI3, we find a type I band alignment that supports transfer of photogenerated carriers across the heterointerface. Light-emitting diodes (LEDs) show electroluminescence from both the CsPbBr3 and CsPbI3 layers with no evidence of ion diffusion during operation. Our approach provides opportunities to design novel all-perovskite heterostructures to facilitate the control of charge and light in optoelectronic applications.
ABSTRACT
Partial body cryotherapy (PBC) is proposed to alleviate symptoms of exercise-induced muscle damage (EIMD) by reducing associated inflammation. No studies have assessed acute PBC exposure on peripheral blood mononuclear cell mobilisation or compared these with cold water immersion (CWI), which may inform how PBC impacts inflammatory processes. This trial examined the impact of a single PBC exposure on circulating peripheral blood mononuclear cells compared to CWI or a control. 26 males were randomised into either PBC (3 min at - 110 to - 140 °C), CWI (3 min at 9 °C), or control (3 min at 24 °C), with blood samples, heart rate, and blood pressure taken before and after exposure. Cytometric analysis determined that CD8+ T-cell populations were significantly elevated after treatments, with PBC increasing CD8+ T cells to a greater degree than either CWI or CON. Natural killer cell counts were also elevated after PBC, with the increase attributed specifically to the CD56loCD16+ cytotoxic subset. This provides the first evidence for the effect of PBC exposure on redistribution of immune cells. An increase in circulating leukocyte subsets such as CD8+ T cells and CD56loCD16+ natural killer cells suggests that PBC may induce a transient mobilisation of lymphocytes. PBC may thus enable a more efficient trafficking of these cells from the circulation to the site of initial cellular insult from exercise, potentially accelerating the process of cellular recovery. This provides novel evidence on the use of PBC as a recovery treatment and may also have applicability in other clinical settings involving the recovery of damaged skeletal muscle.
Subject(s)
CD8-Positive T-Lymphocytes , Leukocytes, Mononuclear , Male , Humans , Cryotherapy , Water , Killer Cells, Natural , Cold Temperature , Immersion , Muscle, Skeletal/physiologyABSTRACT
We describe a Kappa-on-Heavy (KoH) mouse that produces a class of highly diverse, fully human, antibody-like agents. This mouse was made by replacing the germline variable sequences of both the Ig heavy-chain (IgH) and Ig kappa (IgK) loci with the human IgK germline variable sequences, producing antibody-like molecules with an antigen binding site made up of 2 kappa variable domains. These molecules, named KoH bodies, structurally mimic naturally existing Bence-Jones light-chain dimers in their variable domains and remain wild-type in their antibody constant domains. Unlike artificially diversified, nonimmunoglobulin alternative scaffolds (e.g., DARPins), KoH bodies consist of a configuration of normal Ig scaffolds that undergo natural diversification in B cells. Monoclonal KoH bodies have properties similar to those of conventional antibodies but exhibit an enhanced ability to bind small molecules such as the endogenous cardiotonic steroid marinobufagenin (MBG) and nicotine. A comparison of crystal structures of MBG bound to a KoH Fab versus a conventional Fab showed that the KoH body has a much deeper binding pocket, allowing MBG to be held 4 Å further down into the combining site between the 2 variable domains.
Subject(s)
Antibodies/chemistry , Antibodies/immunology , Antigens/immunology , Immunoglobulin Heavy Chains/chemistry , Immunoglobulin Variable Region/chemistry , Immunoglobulin Variable Region/immunology , Immunoglobulin kappa-Chains/chemistry , Animals , Antibodies/genetics , Antibodies/therapeutic use , Base Sequence , Binding Sites, Antibody/genetics , Bufanolides , Genetic Engineering , Humans , Immunoglobulin Heavy Chains/genetics , Immunoglobulin Variable Region/genetics , Immunoglobulin kappa-Chains/genetics , Mice , Models, Molecular , Nicotine , Protein ConformationABSTRACT
Protein glycation is a common, normally innocuous, post-translational modification in therapeutic monoclonal antibodies. However, when glycation occurs on complementarity-determining regions (CDRs) of a therapeutic monoclonal antibody, its biological activities (e.g., potency) may be impacted. Here, we present a comprehensive approach to understanding the mechanism of protein glycation using a bispecific antibody. Cation exchange chromatography and liquid chromatography-mass spectrometry were used to characterize glycation at a lysine residue within a heavy chain (HC) CDR (HC-CDR3-Lys98) of a bispecific antibody. Thermodynamic analysis revealed that this reaction is reversible and can occur under physiological conditions with an apparent affinity of 8-10 mM for a glucose binding to HC-CDR3-Lys98. Results from kinetic analysis demonstrated that this reaction follows Arrhenius behavior in the temperature range of 5°C-45°C and can be well predicted in vitro and in a non-human primate. In addition, this glycation reaction was found to be driven by an unusually low pKa on the ε-amino group of HC-CDR3-Lys98. Van't Hoff analysis and homology modeling suggested that this reaction is enthalpically driven, with this lysine residue surrounded by a microenvironment with low polarity. This study provides, to our knowledge, new insights toward a mechanistic understanding of protein glycation and strategies to mitigate the impact of protein glycation during pharmaceutical development.
Subject(s)
Complementarity Determining Regions , Lysine , Animals , Antibodies, Monoclonal/chemistry , Chromatography, Liquid , Complementarity Determining Regions/chemistry , Complementarity Determining Regions/metabolism , Glycosylation , Kinetics , Lysine/metabolismABSTRACT
It is commonly assumed that charge-carrier transport in doped π-conjugated polymers is dominated by one type of charge carrier, either holes or electrons, as determined by the chemistry of the dopant. Here, through Seebeck coefficient and Hall effect measurements, we show that mobile electrons contribute substantially to charge-carrier transport in π-conjugated polymers that are heavily p-doped with strong electron acceptors. Specifically, the Seebeck coefficient of several p-doped polymers changes sign from positive to negative as the concentration of the oxidizing agents FeCl3 or NOBF4 increase, and Hall effect measurements for the same p-doped polymers reveal that electrons become the dominant delocalized charge carriers. Ultraviolet and inverse photoelectron spectroscopy measurements show that doping with oxidizing agents results in elimination of the transport gap at high doping concentrations. This approach of heavy p-type doping is demonstrated to provide a promising route to high-performance n-type organic thermoelectric materials.
ABSTRACT
Intravitreal (IVT) administration of therapeutics is the standard of care for treatment of back-of-eye disorders. Although a common procedure performed by retinal specialists, IVT administration is associated with unique challenges related to drug product, device and the procedure, which may result in adverse events. Container closure configuration plays a crucial role in maintaining product stability, safety, and efficacy for the intended shelf-life. Careful design of primary container configuration is also important to accurately deliver small volumes (10-100 µL). Over- or under-dosing may lead to undesired adverse events or lack of efficacy resulting in unpredictable and variable clinical responses. IVT drug products have been traditionally presented in glass vials. However, pre-filled syringes offer a more convenient administration option by reducing the number of steps required for dose preparation there by potentially reducing the time demand on the healthcare providers. In addition to primary container selection, product development studies should focus on, among other things, primary container component characterization, material compatibility with the formulation, formulation stability, fill volume determination, extractables/leachables, and terminal sterilization. Ancillary components such as disposable syringes and needles must be carefully selected, and a detailed administration procedure that includes dosing instructions is required to ensure successful administration of the product. Despite significant efforts in improving the drug product and administration procedures, ocular safety concerns such as endophthalmitis, increased intraocular pressure, and presence of silicone floaters have been reported. A systematic review of available literature on container closure and devices for IVT administration can help guide successful product development.
Subject(s)
Drug Delivery Systems/methods , Drug Packaging/methods , Intravitreal Injections/methods , Syringes , Humans , Needles , Pharmaceutical Preparations/administration & dosage , SterilizationABSTRACT
Precise doping of organic semiconductors allows control over the conductivity of these materials, an essential parameter in electronic applications. Although Lewis acids have recently shown promise as dopants for solution-processed polymers, their doping mechanism is not yet fully understood. In this study, we found that B(C6F5)3 is a superior dopant to the other Lewis acids investigated (BF3, BBr3 and AlCl3). Experiments indicate that Lewis acid-base adduct formation with polymers inhibits the doping process. Electron-nuclear double-resonance and nuclear magnetic resonance experiments, together with density functional theory, show that p-type doping occurs by generation of a water-Lewis acid complex with substantial Brønsted acidity, followed by protonation of the polymer backbone and electron transfer from a neutral chain segment to a positively charged, protonated one. This study provides insight into a potential path for protonic acid doping and shows how trace levels of water can transform Lewis acids into powerful Brønsted acids.
ABSTRACT
Photon upconversion employing semiconductor nanocrystals (NCs) makes use of their large and tunable absorption to harvest light in the near-infrared (NIR) wavelengths as well as their small gap between singlet and triplet excited states to reduce energy losses. Here, we report the highest QY (11.8%) thus far for the conversion of NIR to yellow photons by improving the quality of the PbS NC. This high QY was achieved by using highly purified lead and thiourea precursors. This QY is 2.6 times higher than from NCs prepared with commercially available lead and sulfide precursors. Transient absorption spectroscopy reveals two reasons for the enhanced QY: longer intrinsic exciton lifetimes of PbS NCs and the ability to support a longer triplet lifetime for the surface-bound transmitter molecule. Overall, this results in a higher efficiency of triplet exciton transfer from the PbS NC light absorber to the emitter and thus a higher photon upconversion QY.
Subject(s)
Lead/chemistry , Photosensitizing Agents/chemistry , Quantum Dots/chemistry , Sulfides/chemistry , Infrared Rays , Lead/radiation effects , Photosensitizing Agents/radiation effects , Quantum Dots/radiation effects , Sulfides/radiation effectsABSTRACT
PURPOSE: This study investigated non-invasive indices of post-exercise parasympathetic reactivation (using heart rate variability, HRV) and sympathetic withdrawal (using systolic time intervals, STI) following different exercise durations. METHODS: 13 healthy males (age 26.4 ± 4.7 years) cycled at 70% heart rate (HR) reserve for two durations-8 min (SHORT) and 32 min (LONG)-on separate occasions: HRV (including natural logarithm of root mean square of successive differences, Ln-RMSSD) and STI (including pre-ejection period, PEP) were assessed throughout 10 min seated recovery. RESULTS: Exercise HR was similar between SHORT and LONG (146 ± 7 and 147 ± 6 b min-1, respectively; p = 0.173), as was HR deceleration during 10 min recovery (p = 0.199). HR remained elevated above baseline (p < 0.001) throughout recovery for both trials (SHORT 82 ± 13 b min-1; LONG 86 ± 10 b min-1, at 10 min post-exercise). Ln-RMSSD was similar at end-exercise between trials (SHORT 1.10 ± 0.30 ms; LONG 1.05 ± 0.73 ms; p = 0.656), though it recovered more rapidly following SHORT (p = 0.010), with differences apparent from 1 min (SHORT 2.29 ± 1.08 ms; LONG 1.85 ± 0.82 ms; p = 0.005) to 10 min post-exercise (SHORT 2.89 ± 0.80 ms; LONG 2.46 ± 0.70 ms; p = 0.007). Ln-RMSSD remained suppressed below baseline throughout recovery following both trials (p < 0.001). PEP was the same at end exercise for both trials (70 ± 6 ms), with exercise duration having no effect on recovery (p = 0.659). By 10 min post-exercise, PEP increased to 130 ± 21 ms (SHORT) and 131 ± 20 ms (LONG), which was similar to baseline (p ≥ 0.143). CONCLUSIONS: Prolonged exercise duration attenuated the recovery of HRV indices of parasympathetic reactivation, but did not influence STI indices of sympathetic withdrawal. Therefore, duration must be considered when investigating post-exercise HRV. Monitoring these measures simultaneously can provide insights not revealed by underlying HR or either measure alone.
Subject(s)
Heart Rate , Physical Conditioning, Human/methods , Sympathetic Nervous System/physiology , Adult , Blood Pressure , Heart/innervation , Heart/physiology , Humans , Male , Reaction Time , Recovery of FunctionABSTRACT
OBJECTIVE: To assess the prevalence of symptoms of depression, anxiety, and rates of alcohol misuse in elite rugby league players in Australasia. DESIGN: A cross-sectional, epidemiological study with repeated measures. SETTING: Surveys were conducted during the 2015 preseason and in-season. PARTICIPANTS: Four hundred four elite rugby league players participated preseason and 278 players in-season. MAIN OUTCOME MEASURES: Symptoms of depression were measured using the Patient Health Questionnaire-9 scale, symptoms of generalized anxiety disorder (GAD) with the GAD-7 scale, and the Alcohol Use Disorders Identification Test Consumption scale was used to assess hazardous alcohol use. RESULTS: The overall prevalence of depression was 12.6% preseason and 10.1% in-season. Generalized anxiety disorder had a prevalence of 14.6% and 10.1% for these 2 periods. Overall, 68.6% of players had hazardous levels of alcohol use preseason, and 62.8% in-season. There was no significant difference for any of the main outcomes between the periods. Players with a history of mental illnesses had 5.62 greater odds (95% confidence interval [CI], 2.62-12.04) of depression than those without during preseason, and 22.08 greater odds (95% CI, 7.77-62.71) in-season. Players reporting ≥3 previous concussions had 2.02 greater odds (95% CI, 1.07-3.82) of depression than those reporting ≤2 in the preseason sample. CONCLUSIONS: Rugby league players have a lower prevalence of depression compared with studies of the general population and other athletes, but a higher prevalence of GAD, and high rates of alcohol misuse. Clubs may consider implementing regular screening for these conditions. Further prospective research to determine causality of independent factors is required.
Subject(s)
Alcohol Drinking/epidemiology , Anxiety/epidemiology , Depression/epidemiology , Football , Adolescent , Adult , Athletes , Cross-Sectional Studies , Humans , Male , Prevalence , Surveys and Questionnaires , Young AdultABSTRACT
This review aims to evaluate the current body of literature investigating the effect of whole body cryotherapy on recovery after exercise. A systematic search was conducted to investigate the effect of whole body cryotherapy (WBC, exposure to temperatures between -110 to -190°C) on markers of recovery after damaging exercise in healthy, physically active subjects. Of the 16 eligible articles extracted, ten induced muscle damage using controlled exercise in a laboratory setting, while six induced damage during sport-specific training. Results indicated that muscle pain was reduced in 80% of studies following WBC. Two applied studies found recovery of athletic capacity and performance with WBC improved, variables of this nature were also improved in 71% of studies using controlled exercise. Further benefits of WBC treatment included reduction of systemic inflammation and lower concentrations of markers for muscle cell damage. These results suggest that WBC may improve recovery from muscle damage, with multiple exposures more consistently exhibiting improvements in recovery from pain, loss of muscle function, and markers of inflammation and damage. The diversity in muscle damage protocols, exposure timing with regards to exercise, as well as temperatures, duration and frequencies of exposure, make specific recommendations preliminary at present.
Subject(s)
Cryotherapy , Exercise , Myalgia/therapy , Athletic Performance , Humans , Muscle, Skeletal/physiologyABSTRACT
PURPOSE: This study investigated whether short-term heart rate variability (HRV) can be used to differentiate between the immediate recovery periods following three different intensities of preceding exercise. METHODS: 12 males cycled for 8 min at three intensities: LOW (40-45 %), MOD (75-80 %) and HIGH (90-95 %) of heart rate (HR) reserve. HRV was assessed during exercise and throughout 10-min seated recovery. RESULTS: 1-min HR recovery was reduced following greater exercise intensities when expressed as R-R interval (RRI, ms) (p < 0.001), but not b min(-1) (p = 0.217). During exercise, the natural logarithm of root mean square of successive differences (Ln-RMSSD) was higher during LOW (1.66 ± 0.47 ms) relative to MOD (1.14 ± 0.32 ms) and HIGH (1.30 ± 0.25 ms) (p ≤ 0.037). Similar results were observed for high-frequency spectra (Ln-HF-LOW: 2.9 ± 1.0; MOD: 1.6 ± 0.6; HIGH: 1.6 ± 0.3 ms(2), p < 0.001). By 1-min recovery, higher preceding exercise intensities resulted in lower HRV amongst all three intensities for Ln-RMSSD (LOW: 3.45 ± 0.58; MOD: 2.34 ± 0.81; HIGH: 1.66 ± 0.78 ms, p < 0.001) and Ln-HF (LOW: 6.0 ± 1.0; MOD: 4.3 ± 1.4; HIGH: 2.8 ± 1.4 ms(2), p < 0.001). Similarly, by 1-min recovery 'HR-corrected' HRV (Ln-RMSSD: RRI × 10(3)) was different amongst all three intensities (LOW: 3.64 ± 0.49; MOD: 2.90 ± 0.65; HIGH: 2.40 ± 0.67, p < 0.001). These differences were maintained throughout 10-min recovery (p ≤ 0.027). CONCLUSION: Preceding exercise intensity has a graded effect on recovery HRV measures reflecting cardiac vagal activity, even after correcting for the underlying HR. The immediate recovery following exercise is a potentially useful period to investigate autonomic activity, as multiple levels of autonomic activity can be clearly differentiated between using HRV. When investigating post-exercise HRV it is critical to account for the relative exercise intensity.
Subject(s)
Exercise/physiology , Heart Rate , Adult , Analysis of Variance , Autonomic Nervous System/physiology , Humans , Male , Random AllocationABSTRACT
Interfaces between organic electron-donating (D) and electron-accepting (A) materials have the ability to generate charge carriers on illumination. Efficient organic solar cells require a high yield for this process, combined with a minimum of energy losses. Here, we investigate the role of the lowest energy emissive interfacial charge-transfer state (CT1) in the charge generation process. We measure the quantum yield and the electric field dependence of charge generation on excitation of the charge-transfer (CT) state manifold via weakly allowed, low-energy optical transitions. For a wide range of photovoltaic devices based on polymer:fullerene, small-molecule:C60 and polymer:polymer blends, our study reveals that the internal quantum efficiency (IQE) is essentially independent of whether or not D, A or CT states with an energy higher than that of CT1 are excited. The best materials systems show an IQE higher than 90% without the need for excess electronic or vibrational energy.
ABSTRACT
The performance of organic photovoltaic (OPV) material systems are hypothesized to depend strongly on the intermolecular arrangements at the donor:fullerene interfaces. A review of some of the most efficient polymers utilized in polymer:fullerene PV devices, combined with an analysis of reported polymer donor materials wherein the same conjugated backbone was used with varying alkyl substituents, supports this hypothesis. Specifically, the literature shows that higher-performing donor-acceptor type polymers generally have acceptor moieties that are sterically accessible for interactions with the fullerene derivative, whereas the corresponding donor moieties tend to have branched alkyl substituents that sterically hinder interactions with the fullerene. To further explore the idea that the most beneficial polymer:fullerene arrangement involves the fullerene docking with the acceptor moiety, a family of benzo[1,2-b:4,5-b']dithiophene-thieno[3,4-c]pyrrole-4,6-dione polymers (PBDTTPD derivatives) was synthesized and tested in a variety of PV device types with vastly different aggregation states of the polymer. In agreement with our hypothesis, the PBDTTPD derivative with a more sterically accessible acceptor moiety and a more sterically hindered donor moiety shows the highest performance in bulk-heterojunction, bilayer, and low-polymer concentration PV devices where fullerene derivatives serve as the electron-accepting materials. Furthermore, external quantum efficiency measurements of the charge-transfer state and solid-state two-dimensional (2D) (13)C{(1)H} heteronuclear correlation (HETCOR) NMR analyses support that a specific polymer:fullerene arrangement is present for the highest performing PBDTTPD derivative, in which the fullerene is in closer proximity to the acceptor moiety of the polymer. This work demonstrates that the polymer:fullerene arrangement and resulting intermolecular interactions may be key factors in determining the performance of OPV material systems.
ABSTRACT
Theoretical and experimental studies suggest that energetic offsets between the charge transport energy levels in different morphological phases of polymer:fullerene bulk heterojunctions may improve charge separation and reduce recombination in polymer solar cells (PSCs). In this work, we use cyclic voltammetry, UV-vis absorption, and ultraviolet photoelectron spectroscopy to characterize hole energy levels in the polymer phases of polymer:fullerene bulk heterojunctions. We observe an energetic offset of up to 150 meV between amorphous and crystalline polymer due to bandgap widening associated primarily with changes in polymer conjugation length. We also observe an energetic offset of up to 350 meV associated with polymer:fullerene intermolecular interactions. The first effect has been widely observed, but the second effect is not always considered despite being larger in magnitude for some systems. These energy level shifts may play a major role in PSC performance and must be thoroughly characterized for a complete understanding of PSC function.
ABSTRACT
OBJECTIVE: To evaluate the effectiveness of low-intensity pulsed ultrasound (LIPUS) for the improvement of lower limb bone stress injuries in a civilian population. DESIGN: A prospective, randomized, double-blinded, placebo-controlled trial to compare LIPUS with placebo. SETTING: Civilian private practice population in Sydney, Australia. PARTICIPANTS: Subjects were recruited if a grade II-IV bone stress injury was diagnosed on magnetic resonance imaging (MRI) of either the postero-medial tibia, fibula or second, third, or fourth metatarsal. Subjects of all levels of sporting activity were included. Thirty subjects were initially recruited, and 23 subjects were included in the final analysis. INTERVENTIONS: Subjects were randomized into either the treatment or placebo arm and matched to the site of injury (tibia, fibula, or metatarsal). Subjects in both arms used either treatment or placebo devices for 20 minutes daily for 4 weeks. MAIN OUTCOME MEASURES: Six clinical parameters (night pain, pain at rest, pain on walking, pain with running, tenderness, and pain with single leg hop) were compared before and after intervention. The changes in MRI grade and bone marrow edema size were also compared. RESULTS: There were no significant differences between the treatment and placebo conditions for changes in MRI grading (2.2 vs 2.4, P = 0.776) or bone marrow edema size (3 vs 4.1, P = 0.271). There were no significant differences between the treatment and placebo conditions for the 6 clinical parameters. CONCLUSIONS: Low-intensity pulsed ultrasound was found not to be an effective treatment for the healing of lower limb bone stress injuries in this study. However, this was measured over a relatively short duration of 4 weeks in a small, mostly female population. CLINICAL RELEVANCE: This double-blinded, randomized, placebo-controlled trial has shown that LIPUS is not an effective treatment for lower limb bone stress injuries.