Long-Term Effectiveness and Safety of Dutasteride versus Finasteride in Patients with Male Androgenic Alopecia in South Korea: A Multicentre Chart Review Study.

BACKGROUND: Dutasteride improves hair growth compared with finasteride in male androgenic alopecia (AGA) and is well tolerated. However, real-world evidence for long-term dutasteride use in AGA is lacking. OBJECTIVE: To describe baseline characteristics, treatment patterns and long-term safety and effectiveness of dutasteride versus finasteride. METHODS: This was a multicentre, retrospective medical chart review study conducted in South Korea. The index date was the first prescription of dutasteride or finasteride. Baseline characteristics were assessed 6 months prior to index. Safety and effectiveness (improvements in basic and specific [BASP] classification) data were collected from index throughout the observation period. RESULTS: Overall, 600 male adult patients were included (dutasteride, n=295; finasteride, n=305). Dutasteride-treated patients were older (p<0.001) and more likely to have moderate/severe BASP classification at baseline (p=0.010) compared with finasteride-treated patients. Among patients treated with recommended, on-label dosing exclusively (n=535: dutasteride, n=250; finasteride, n=285), dutasteride-treated patients showed greater improvement in hair growth than finasteride-treated patients, as measured by the BASP basic M classification (adjusted incidence rate ratio [95% confidence interval]: 2.06 [1.08, 3.95]; p=0.029). Among this same subset, overall occurrence of adverse events (AEs) during the observation period were not statistically equivalent between groups (dutasteride 7.6%, finasteride 10.5%; p=0.201), although reports of AEs of special interest were equivalent (p<0.001). CONCLUSION: Dutasteride showed greater effectiveness than finasteride in improving BASP classification in treating male AGA and had a similar or possibly lower occurrence of overall AEs. Dutasteride may provide an effective and safe treatment option for male patients with AGA.

Contact Conductance Governs Metallicity in Conducting Metal Oxide Nanocrystal Films.

Although colloidal nanoparticles hold promise for fabricating electronic components, the properties of nanoparticle-derived materials can be unpredictable. Materials made from metallic nanocrystals exhibit a variety of transport behavior ranging from insulators, with internanocrystal contacts acting as electron transport bottlenecks, to conventional metals, where phonon scattering limits electron mobility. The insulator-metal transition (IMT) in nanocrystal films is thought to be determined by contact conductance. Meanwhile, criteria are lacking to predict the characteristic transport behavior of metallic nanocrystal films beyond this threshold. Using a library of transparent conducting tin-doped indium oxide nanocrystal films with varied electron concentration, size, and contact area, we assess the IMT as it depends on contact conductance and show how contact conductance is also key to predicting the temperature-dependence of conductivity in metallic films. The results establish a phase diagram for electron transport behavior that can guide the creation of metallic conducting materials from nanocrystal building blocks.

Thermodynamic non-ideality in charge regulation of weak polyelectrolytes.

Polymer ionization differs from that for their monomeric counterparts due to intramolecular correlations. Such effects are conventionally described in terms of the site-binding model that accounts for short-range interactions between neighboring sites. With an apparent equilibrium constant for each ionizable group and the nearest-neighbor energy as adjustable parameters, the site-binding method is useful to correlate experimental titration curves when the site-site interactions are insignificant at long ranges. This work aims to describe the electrostatic behavior of weak polyelectrolytes in aqueous solutions on the basis of the intrinsic equilibrium constants of the individual ionizable groups and solution conditions underlying the thermodynamic non-ideality. A molecular thermodynamic model is proposed for the protonation of weak polyelectrolytes by incorporating classical density functional theory into the site-binding model to account for the effects of the local ionic environment on both inter-chain and intra-chain correlations. By an extensive comparison of theoretical predictions with experimental titration curves, we demonstrate that the thermodynamic model is able to quantify the ionization behavior of weak polyelectrolytes over a broad range of molecular architectures and solution conditions.

Understanding the Hydrothermal Formation of NaNbO3: Its Full Reaction Scheme and Kinetics.

Sodium niobate (NaNbO3) attracts attention for its great potential in a variety of applications, for instance, due to its unique optical properties. Still, optimization of its synthetic procedures is hard due to the lack of understanding of the formation mechanism under hydrothermal conditions. Through in situ X-ray diffraction, hydrothermal synthesis of NaNbO3 was observed in real time, enabling the investigation of the reaction kinetics and mechanisms with respect to temperature and NaOH concentration and the resulting effect on the product crystallite size and structure. Several intermediate phases were observed, and the relationship between them, depending on temperature, time, and NaOH concentration, was established. The reaction mechanism involved a gradual change of the local structure of the solid Nb2O5 precursor upon suspending it in NaOH solutions. Heating gave a full transformation of the precursor to HNa7Nb6O19·15H2O, which destabilized before new polyoxoniobates appeared, whose structure depended on the NaOH concentration. Following these polyoxoniobates, Na2Nb2O6·H2O formed, which dehydrated at temperatures ≥285 °C, before converting to the final phase, NaNbO3. The total reaction rate increased with decreasing NaOH concentration and increasing temperature. Two distinctly different growth regimes for NaNbO3 were observed, depending on the observed phase evolution, for temperatures below and above ≈285 °C. Below this temperature, the growth of NaNbO3 was independent of the reaction temperature and the NaOH concentration, while for temperatures ≥285 °C, the temperature-dependent crystallite size showed the characteristics of a typical dissolution-precipitation mechanism.

Ising density functional theory for weak polyelectrolytes with strong coupling of ionization and intrachain correlations.

We report a theoretical framework for weak polyelectrolytes by combining the polymer density functional theory with the Ising model for charge regulation. The so-called Ising density functional theory provides an accurate description of the effects of polymer conformation on the ionization of individual segments and is able to account for both the intra- and interchain correlations due to the excluded-volume effects, chain connectivity, and electrostatic interactions. Theoretical predictions of the titration behavior and microscopic structure of ionizable polymers are found to be in excellent agreement with the experiment.

Modeling Surface Charge Regulation of Colloidal Particles in Aqueous Solutions.

Colloidal particles are mostly charged in an aqueous solution because of the protonation or deprotonation of ionizable groups on the surface. The surface charge density reflects a complex interplay of ion distributions within the electric double layer and the surface reaction equilibrium. In this work, we present a coarse-grained model to describe the charge regulation of various colloidal systems by an explicit consideration of the inhomogeneous ion distributions and surface reactions. With the primitive model for aqueous solutions and equilibrium constants for surface reactions as the inputs, the theoretical model is able to make quantitative predictions of the surface-charge densities and zeta potentials for diverse colloidal particles over a wide range of pH and ionic conditions. By accounting for the ionic size effects and electrostatic correlations, our model is applicable to systems with multivalent ions that exhibit charge inversion and provides a faithful description of the interfacial properties without evoking the empirical Stern capacitance or specific ion adsorptions.

Universal Gelation of Metal Oxide Nanocrystals via Depletion Attractions.

Nanocrystal gelation provides a powerful framework to translate nanoscale properties into bulk materials and to engineer emergent properties through the assembled microstructure. However, many established gelation strategies rely on chemical reactions and specific interactions, e.g., stabilizing ligands or ions on the nanocrystals' surfaces, and are therefore not easily transferable. Here, we report a general gelation strategy via nonspecific and purely entropic depletion attractions applied to three types of metal oxide nanocrystals. The gelation thresholds of two compositionally distinct spherical nanocrystals agree quantitatively, demonstrating the adaptability of the approach for different chemistries. Consistent with theoretical phase behavior predictions, nanocrystal cubes form gels at a lower polymer concentration than nanocrystal spheres, allowing shape to serve as a handle to control gelation. These results suggest that the fundamental underpinnings of depletion-driven assembly, traditionally associated with larger colloidal particles, are also applicable at the nanoscale.

Mapping the phase behavior of coacervate-driven self-assembly in diblock copolyelectrolytes.

Oppositely-charged polymers can undergo an associative phase separation process known as complex coacervation, which is driven by the electrostatic attraction between the two polymer species. This driving force for phase separation can be harnessed to drive self-assembly, via pairs of block copolyelectrolytes with opposite charge and thus favorable coulombic interactions. There are few predictions of coacervate self-assembly phase behavior due to the wide variety of molecular and environmental parameters, along with fundamental theoretical challenges. In this paper, we use recent advances in coacervate theory to predict the solution-phase assembly of diblock polyelectrolyte pairs for a number of molecular design parameters (charged block fraction, polymer length). Phase diagrams show that self-assembly occurs at high polymer, low salt concentrations for a range of charge block fractions. We show that we qualitatively obtain limiting results seen in the experimental literature, including the emergence of a high polymer-fraction reentrant transition that gives rise to a self-compatibilized homopolymer coacervate behavior at the limit of high charge block fraction. In intermediate charge block fractions, we draw an analogy between the role of salt concentration in coacervation-driven assembly and the role of temperature in χ-driven assembly. We also explore salt partitioning between microphase separated domains in block copolyelectrolytes, with parallels to homopolyelectrolyte coacervation.

Gelation of plasmonic metal oxide nanocrystals by polymer-induced depletion attractions.

Gelation of colloidal nanocrystals emerged as a strategy to preserve inherent nanoscale properties in multiscale architectures. However, available gelation methods to directly form self-supported nanocrystal networks struggle to reliably control nanoscale optical phenomena such as photoluminescence and localized surface plasmon resonance (LSPR) across nanocrystal systems due to processing variabilities. Here, we report on an alternative gelation method based on physical internanocrystal interactions: short-range depletion attractions balanced by long-range electrostatic repulsions. The latter are established by removing the native organic ligands that passivate tin-doped indium oxide (ITO) nanocrystals while the former are introduced by mixing with small PEG chains. As we incorporate increasing concentrations of PEG, we observe a reentrant phase behavior featuring two favorable gelation windows; the first arises from bridging effects while the second is attributed to depletion attractions according to phase behavior predicted by our unified theoretical model. Our assembled nanocrystals remain discrete within the gel network, based on X-ray scattering and high-resolution transmission electron microscopy. The infrared optical response of the gels is reflective of both the nanocrystal building blocks and the network architecture, being characteristic of ITO nanocrystals' LSPR with coupling interactions between neighboring nanocrystals.

Controlling Morphology in Polycrystalline Films by Nucleation and Growth from Metastable Nanocrystals.

Solution processing of polycrystalline compound semiconductor thin film using nanocrystals as a precursor is considered one of the most promising and economically viable routes for future large-area manufacturing. However, in polycrystalline compound semiconductor films such as Cu2ZnSnS4 (CZTS), grain size, and the respective grain boundaries play a key role in dictating the optoelectronic properties. Various strategies have been employed previously in tailoring the grain size and boundaries (such as ligand exchange) but most require postdeposition thermal annealing at high temperature in the presence of grain growth directing agents (selenium or sulfur vapor with/without Na, K, etc.) to enlarge the grains through sintering. Here, we show a different strategy of controlling grain size by tuning the kinetics of nucleation and the subsequent grain growth in CZTS nanocrystal thin films during a crystalline phase transition. We demonstrate that the activation energy for the phase transition can be varied by utilizing different shapes (spherical and nanorod) of nanocrystals with similar size, composition, and surface chemistry leading to different densities of nucleation sites and, thereby, different grain sizes in the films. Additionally, exchanging the native organic ligands for inorganic surface ligands changes the activation energy for the phase change and substantially changes the grain growth dynamics, while also compositionally modifying the resulting film. This combined approach of using nucleation and growth dynamics and surface chemistry enables us to tune the grain size of polycrystalline CZTS films and customize their electronic properties by compositional engineering.

A randomized, open-label study to evaluate an intermittent dosing regimen of fluticasone propionate 0.05% cream in combination with regular emollient skin care in reducing the risk of relapse in pediatric patients with stabilized atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing disease that requires maintenance treatment. This study examined the efficacy and safety of extended intermittent fluticasone propionate (FP) 0.05% cream, with emollient, vs emollient alone in children with AD. METHODS: Eligible patients (aged 1-17 years) received FP 0.05% cream twice daily for 4 weeks (acute phase) then randomized (1:1) to FP 0.05% cream once daily, twice per week plus emollient (Group A) or emollient alone (Group B) for up to 20 weeks (maintenance phase). Primary endpoint was time to first AD relapse. Safety was assessed throughout. RESULTS: This study enrolled 123 patients into the acute phase, of whom 107 entered the maintenance phase (Group A: 54; Group B; 53). Three patients (5.6%) in Group A and 30 (56.6%) in Group B experienced relapse (maintenance phase). Due to a low number of relapses, median time to first relapse could not be calculated for Group A; in Group B, it was 142 d (95% CI: 50, 150; p < .0001 vs Group A). FP and emollient were well tolerated. CONCLUSIONS: In pediatric patients with stabilized AD, FP 0.05% cream plus emollient (for AD maintenance treatment) significantly reduced the risk of relapse vs emollient alone.

Template-Free Mesoporous Electrochromic Films on Flexible Substrates from Tungsten Oxide Nanorods.

Low-temperature processed mesoporous nanocrystal thin films are platforms for fabricating functional composite thin films on flexible substrates. Using a random arrangement of anisotropic nanocrystals can be a facile solution to generate pores without templates. However, the tendency for anisotropic particles to spontaneously assemble into a compact structure must be overcome. Here, we present a method to achieve random networking of nanorods during solution phase deposition by switching their ligand-stabilized colloidal nature into a charge-stabilized nature by a ligand-stripping chemistry. Ligand-stripped tungsten suboxide (WO2.72) nanorods result in uniform mesoporous thin films owing to repulsive electrostatic forces preventing nanorods from densely packing. Porosity and pore size distribution of thin films are controlled by changing the aspect ratio of the nanorods. This template-free mesoporous structure, achieved without annealing, provides a framework for introducing guest components, therefore enabling our fabrication of inorganic nanocomposite electrochromic films on flexible substrates. Following infilling of niobium polyoxometalate clusters into pores and successive chemical condensation, a WOx-NbOx composite film is produced that selectively controls visible and near-infrared light transmittance without any annealing required. The composite shows rapid switching kinetics and can be stably cycled between optical states over 2000 times. This simple strategy of using anisotropic nanocrystals gives insight into mesoporous thin film fabrication with broader applications for flexible devices.

Dopant Mediated Assembly of Cu2ZnSnS4 Nanorods into Atomically Coupled 2D Sheets in Solution.

Assembly of anisotropic nanocrystals into ordered superstructures is an area of intense research interest due to its relevance to bring nanocrystal properties to macroscopic length scales and to impart additional collective properties owing to the superstructure. Numerous routes have been explored to assemble such nanocrystal superstructures ranging from self-directed to external field-directed methods. Most of the approaches require sensitive control of experimental parameters that are largely environmental and require extra processing steps, increasing complexity and limiting reproducibility. Here, we demonstrate a simple approach to assemble colloidal nanorods in situ, wherein dopant incorporation during the particle synthesis results in the formation of preassembled 2D sheets of close-packed ordered arrays of vertically oriented nanorods in solution.

Resonant Coupling between Molecular Vibrations and Localized Surface Plasmon Resonance of Faceted Metal Oxide Nanocrystals.

Doped metal oxides are plasmonic materials that boast both synthetic and postsynthetic spectral tunability. They have already enabled promising smart window and optoelectronic technologies and have been proposed for use in surface enhanced infrared absorption spectroscopy (SEIRA) and sensing applications. Herein, we report the first step toward realization of the former utilizing cubic F and Sn codoped In2O3 nanocrystals (NCs) to couple to the C-H vibration of surface-bound oleate ligands. Electron energy loss spectroscopy is used to map the strong near-field enhancement around these NCs that enables localized surface plasmon resonance (LSPR) coupling between adjacent nanocrystals and LSPR-molecular vibration coupling. Fourier transform infrared spectroscopy measurements and finite element simulations are applied to observe and explain the nature of the coupling phenomena, specifically addressing coupling in mesoscale assembled films. The Fano line shape signatures of LSPR-coupled molecular vibrations are rationalized with two-port temporal coupled mode theory. With this combined theoretical and experimental approach, we describe the influence of coupling strength and relative detuning between the molecular vibration and LSPR on the enhancement factor and further explain the basis of the observed Fano line shape by deconvoluting the combined response of the LSPR and molecular vibration in transmission, absorption and reflection. This study therefore illustrates various factors involved in determining the LSPR-LSPR and LSPR-molecular vibration coupling for metal oxide materials and provides a fundamental basis for the design of sensing or SEIRA substrates.

Ordering in Polymer Micelle-Directed Assemblies of Colloidal Nanocrystals.

Assembly of presynthesized nanocrystals by block copolymer micelles can be rationalized by the incorporation of nanocrystals into micellar coronas of constant width. As determined by quantitative analysis using small-angle X-ray scattering, high loading of small nanocrystals yields composites exhibiting order on two length scales, whereas intermediate loading of nanocrystals larger than the coronal width produces single nanocrystal networks. The resulting structures obey expectations of thermodynamically driven assembly on the nanocrystal length scale, whereas kinetically frozen packing principles dictate order on the polymer micelle length scale.

Linking Semiconductor Nanocrystals into Gel Networks through All-Inorganic Bridges.

For colloidal semiconductor nanocrystals (NCs), replacement of insulating organic capping ligands with chemically diverse inorganic clusters enables the development of functional solids in which adjacent NCs are strongly coupled. Yet controlled assembly methods are lacking to direct the arrangement of charged, inorganic cluster-capped NCs into open networks. Herein, we introduce coordination bonds between the clusters capping the NCs thus linking the NCs into highly open gel networks. As linking cations (Pt(2+)) are added to dilute (under 1 vol %) chalcogenidometallate-capped CdSe NC dispersions, the NCs first form clusters, then gels with viscoelastic properties. The phase behavior of the gels for variable [Pt(2+)] suggests they may represent nanoscale analogues of bridged particle gels, which have been observed to form in certain polymer colloidal suspensions.

Nanocomposite Architecture for Rapid, Spectrally-Selective Electrochromic Modulation of Solar Transmittance.

Two active electrochromic materials, vacancy-doped tungsten oxide (WO(3-x)) nanocrystals and amorphous niobium oxide (NbOx) glass are arranged into a mesostructured architecture. In a strategy applicable across electrochemical applications, the critical dimensions and interfacial connections in the nanocomposite are designed to optimize pathways for electrochemical charging and discharging. The result is an unprecedented optical range for modulation of visible and near-infrared solar radiation with rapid switching kinetics that indicate the WO(3-x) nanocrystal framework effectively pumps charge out of the normally sluggish NbOx glass. The material is durable for at least 2000 electrochemical cycles.

Cross-clade immunogenicity and antigen-sparing with an AS03(A)-adjuvanted prepandemic influenza vaccine in a Thai population.

OBJECTIVE: The present study (NCT00449670) in Asian subjects (18-60 years) evaluated the manufacturing consistency of four formulations of 3.75 mg AS03(A)-adjuvanted H5N1 influenza vaccine, in terms of post-immunization Hemagglutination Inhibition (HI) titers against the A/Vietnam/1194/2004 and A/Indonesia/05/2005 strains. The immunogenicity and safety of the vaccine in the Thai population are reported herein. MATERIAL AND METHOD: Subjects were randomized (2:2:2:2.:1:1) between four vaccine groups and two control groups to receive two doses of either the AS03(A)-adjuvanted or non-adjuvanted H5N1 vaccine formulations, 21 days apart. Sera were assayed for HI antibody titers against the two strains. RESULTS: After the second dose of AS03(A)-adjuvanted vaccine, 94.2% subjects in the H5N1-AS03(A) groups seroconverted and 94.9% subjects were seroprotected against the A/Vietnam/1194/2004 strain. Cross-clade immune response against the A/Indonesia/05/2005 strain was observed. All vaccine formulations had an acceptable safety profile. CONCLUSION: This antigen-sparing AS03(A)-adjuvanted influenza vaccine could be a suitable candidate for combating and mitigating future influenza pandemics.