Repeated intravenous cardiosphere-derived cell therapy in late-stage Duchenne muscular dystrophy (HOPE-2): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.

BACKGROUND: Cardiosphere-derived cells (CDCs) ameliorate skeletal and cardiac muscle deterioration in experimental models of Duchenne muscular dystrophy. The HOPE-2 trial examined the safety and efficacy of sequential intravenous infusions of human allogeneic CDCs in late-stage Duchenne muscular dystrophy. METHODS: In this multicentre, randomised, double-blind, placebo-controlled, phase 2 trial, patients with Duchenne muscular dystrophy, aged 10 years or older with moderate upper limb impairment, were enrolled at seven centres in the USA. Patients were randomly assigned (1:1) using stratified permuted blocks to receive CAP-1002 (1·5 × 108 CDCs) or placebo intravenously every 3 months for a total of four infusions. Clinicians, caregivers, patients, and clinical operations personnel were fully masked to treatment groups. The primary outcome was the change in mid-level elbow Performance of Upper Limb version 1.2 (PUL 1.2) score at 12 months, assessed in the intention-to-treat population. Safety was assessed in all individuals who received an investigational product. This trial is registered with ClinicalTrials.gov, NCT03406780. FINDINGS: Between March 1, 2018, and March 31, 2020, 26 male patients with Duchenne muscular dystrophy were enrolled, of whom eight were randomly assigned to the CAP-1002 group and 12 to the placebo group (six were not randomised due to screening failure). In patients who had a post-treatment PUL 1.2 assessment (eight in the CAP-1002 group and 11 in the placebo group), the mean 12-month change from baseline in mid-level elbow PUL1.2 favoured CAP-1002 over placebo (percentile difference 36·2, 95% CI 12·7-59·7; difference of 2·6 points; p=0·014). Infusion-related hypersensitivity reactions without long-term sequelae were observed in three patients, with one patient discontinuing therapy due to a severe allergic reaction. No other major adverse reactions were noted, and no deaths occurred. INTERPRETATION: CAP-1002 cell therapy appears to be safe and effective in reducing deterioration of upper limb function in patients with late-stage Duchenne muscular dystrophy. Various measures of cardiac function and structure were also improved in the CAP-1002 group compared with the placebo group. Longer-term extension studies are needed to confirm the therapeutic durability and safety of CAP-1002 beyond 12 months for the treatment of skeletal myopathy and cardiomyopathy in Duchenne muscular dystrophy. FUNDING: Capricor Therapeutics.

Lifetime dynamics of plasmons in the few-atom limit.

Polycyclic aromatic hydrocarbon (PAH) molecules are essentially graphene in the subnanometer limit, typically consisting of 50 or fewer atoms. With the addition or removal of a single electron, these molecules can support molecular plasmon (collective) resonances in the visible region of the spectrum. Here, we probe the plasmon dynamics in these quantum systems by measuring the excited-state lifetime of three negatively charged PAH molecules: anthanthrene, benzo[ghi]perylene, and perylene. In contrast to the molecules in their neutral state, these three systems exhibit far more rapid decay dynamics due to the deexcitation of multiple electron-hole pairs through molecular plasmon "dephasing" and vibrational relaxation. This study provides a look into the distinction between collective and single-electron excitation dynamics in the purely quantum limit and introduces a conceptual framework with which to visualize molecular plasmon decay.

Plasmon-induced selective carbon dioxide conversion on earth-abundant aluminum-cuprous oxide antenna-reactor nanoparticles.

The rational combination of plasmonic nanoantennas with active transition metal-based catalysts, known as 'antenna-reactor' nanostructures, holds promise to expand the scope of chemical reactions possible with plasmonic photocatalysis. Here, we report earth-abundant embedded aluminum in cuprous oxide antenna-reactor heterostructures that operate more effectively and selectively for the reverse water-gas shift reaction under milder illumination than in conventional thermal conditions. Through rigorous comparison of the spatial temperature profile, optical absorption, and integrated electric field enhancement of the catalyst, we have been able to distinguish between competing photothermal and hot-carrier driven mechanistic pathways. The antenna-reactor geometry efficiently harnesses the plasmon resonance of aluminum to supply energetic hot-carriers and increases optical absorption in cuprous oxide for selective carbon dioxide conversion to carbon monoxide with visible light. The transition from noble metals to aluminum based antenna-reactor heterostructures in plasmonic photocatalysis provides a sustainable route to high-value chemicals and reaffirms the practical potential of plasmon-mediated chemical transformations.Plasmon-enhanced photocatalysis holds promise for the control of chemical reactions. Here the authors report an Al@Cu2O heterostructure based on earth abundant materials to transform CO2 into CO at significantly milder conditions.

Nanophotonics-enabled solar membrane distillation for off-grid water purification.

With more than a billion people lacking accessible drinking water, there is a critical need to convert nonpotable sources such as seawater to water suitable for human use. However, energy requirements of desalination plants account for half their operating costs, so alternative, lower energy approaches are equally critical. Membrane distillation (MD) has shown potential due to its low operating temperature and pressure requirements, but the requirement of heating the input water makes it energy intensive. Here, we demonstrate nanophotonics-enabled solar membrane distillation (NESMD), where highly localized photothermal heating induced by solar illumination alone drives the distillation process, entirely eliminating the requirement of heating the input water. Unlike MD, NESMD can be scaled to larger systems and shows increased efficiencies with decreased input flow velocities. Along with its increased efficiency at higher ambient temperatures, these properties all point to NESMD as a promising solution for household- or community-scale desalination.

Balancing Near-Field Enhancement, Absorption, and Scattering for Effective Antenna-Reactor Plasmonic Photocatalysis.

Efficient photocatalysis requires multifunctional materials that absorb photons and generate energetic charge carriers at catalytic active sites to facilitate a desired chemical reaction. Antenna-reactor complexes are an emerging multifunctional photocatalytic structure where the strong, localized near field of the plasmonic metal nanoparticle (e.g., Ag) is coupled to the catalytic properties of the nonplasmonic metal nanoparticle (e.g., Pt) to enable chemical transformations. With an eye toward sustainable solar driven photocatalysis, we investigate how the structure of antenna-reactor complexes governs their photocatalytic activity in the light-limited regime, where all photons need to be effectively utilized. By synthesizing core@shell/satellite (Ag@SiO2/Pt) antenna-reactor complexes with varying Ag nanoparticle diameters and performing photocatalytic CO oxidation, we observed plasmon-enhanced photocatalysis only for antenna-reactor complexes with antenna components of intermediate sizes (25 and 50 nm). Optimal photocatalytic performance was shown to be determined by a balance between maximized local field enhancements at the catalytically active Pt surface, minimized collective scattering of photons out of the catalyst bed by the complexes, and minimal light absorption in the Ag nanoparticle antenna. These results elucidate the critical aspects of local field enhancement, light scattering, and absorption in plasmonic photocatalyst design, especially under light-limited illumination conditions.

Understanding Resonant Light-Triggered DNA Release from Plasmonic Nanoparticles.

Nanoparticle-based platforms for gene therapy and drug delivery are gaining popularity for cancer treatment. To improve therapeutic selectivity, one important strategy is to remotely trigger the release of a therapeutic cargo from a specially designed gene- or drug-laden near-infrared (NIR) absorbing gold nanoparticle complex with NIR light. While there have been multiple demonstrations of NIR nanoparticle-based release platforms, our understanding of how light-triggered release works in such complexes is still limited. Here, we investigate the specific mechanisms of DNA release from plasmonic nanoparticle complexes using continuous wave (CW) and femtosecond pulsed lasers. We find that the characteristics of nanoparticle-based DNA release vary profoundly from the same nanoparticle complex, depending on the type of laser excitation. CW laser illumination drives the photothermal release of dehybridized single-stranded DNA, while pulsed-laser excitation results in double-stranded DNA release by cleavage of the Au-S bond, with negligible local heating. This dramatic difference in DNA release from the same DNA-nanoparticle complex has very important implications in the development of NIR-triggered gene or drug delivery nanocomplexes.

Imaging through plasmonic nanoparticles.

The optical properties of metallic nanoparticles with plasmon resonances have been studied extensively, typically by measuring the transmission of light, as a function of wavelength, through a nanoparticle suspension. One question that has not yet been addressed, however, is how an image is transmitted through such a suspension of absorber-scatterers, in other words, how the various spatial frequencies are attenuated as they pass through the nanoparticle host medium. Here, we examine how the optical properties of a suspension of plasmonic nanoparticles affect the transmitted image. We use two distinct ways to assess transmitted image quality: the structural similarity index (SSIM), a perceptual distortion metric based on the human visual system, and the modulation transfer function (MTF), which assesses the resolvable spatial frequencies. We show that perceived image quality, as well as spatial resolution, are both dependent on the scattering and absorption cross-sections of the constituent nanoparticles. Surprisingly, we observe a nonlinear dependence of image quality on optical density by varying optical path length and nanoparticle concentration. This work is a first step toward understanding the requirements for visualizing and resolving objects through media consisting of subwavelength absorber-scatterer structures, an approach that should also prove useful in the assessment of metamaterial or metasurface-based optical imaging systems.

Toward Surface Plasmon-Enhanced Optical Parametric Amplification (SPOPA) with Engineered Nanoparticles: A Nanoscale Tunable Infrared Source.

Active optical processes such as amplification and stimulated emission promise to play just as important a role in nanoscale optics as they have in mainstream modern optics. The ability of metallic nanostructures to enhance optical nonlinearities at the nanoscale has been shown for a number of nonlinear and active processes; however, one important process yet to be seen is optical parametric amplification. Here, we report the demonstration of surface plasmon-enhanced difference frequency generation by integration of a nonlinear optical medium, BaTiO3, in nanocrystalline form within a plasmonic nanocavity. These nanoengineered composite structures support resonances at pump, signal, and idler frequencies, providing large enhancements of the confined fields and efficient coupling of the wavelength-converted idler radiation to the far-field. This nanocomplex works as a nanoscale tunable infrared light source and paves the way for the design and fabrication of a surface plasmon-enhanced optical parametric amplifier.

The medical schools outcomes database project: Australian medical student characteristics.

BACKGROUND: Global medical workforce requirements highlight the need for effective workforce planning, with the overall aims being to alleviate doctor shortages and prevent maldistribution. The Medical Schools Outcomes Database and Longitudinal Tracking (MSOD) Project provides a foundation for evaluating outcomes of medical education programs against specified workforce objectives (including rural and areas of workforce needs), assisting in medical workforce planning, and provision of a national research resource. This paper describes the methodology and baseline results for the MSOD project. METHODS: The MSOD Project is a prospective longitudinal multiple-cohort study. The project invites all commencing and completing Australian medical students to complete short questionnaires. Participants are then asked to participate in four follow-up surveys at 1, 3, 5 and 8 years after graduation. RESULTS: Since 2005, 30,635 responses for medical students (22,126 commencing students and 8,509 completing students) in Australia have been collected. To date, overall eligible cohort response rates are 91% for commencing students, and 83% for completing students. Eighty three percent of completing medical student respondents had also completed a commencing questionnaire.Approximately 80% of medical students at Australian medical schools are Australian citizens. Australian medical schools have only small proportions of Indigenous students. One third of medical students speak a language other than English at home.The top three vocational choices for commencing medical students were surgery, paediatrics and child health and general practice. The top three vocational choices for completing students were surgery, adult medicine/ physician, and general practice. Overall, 75.7% of medical students changed their first career preference from commencement to exit from medical school.Most commencing and completing medical students wish to have their future medical practice in capital cities or in major urban centers. Only 8.1% of commencing students and 4.6% of completing students stated an intention to have their future medical practice in smaller towns and small communities. CONCLUSIONS: The MSOD longitudinal project is now an established national resource that is beginning to generate significant research outputs, along with providing key information for workforce planning and policy makers. The project has now expanded to enrol New Zealand medical students.

Nanoparticles heat through light localization.

Aqueous solutions containing light-absorbing nanoparticles have recently been shown to produce steam at high efficiencies upon solar illumination, even when the temperature of the bulk fluid volume remains far below its boiling point. Here we show that this phenomenon is due to a collective effect mediated by multiple light scattering from the dispersed nanoparticles. Randomly positioned nanoparticles that both scatter and absorb light are able to concentrate light energy into mesoscale volumes near the illuminated surface of the liquid. The resulting light absorption creates intense localized heating and efficient vaporization of the surrounding liquid. Light trapping-induced localized heating provides the mechanism for low-temperature light-induced steam generation and is consistent with classical heat transfer.