Atomistic mechanism of structural and volume relaxation below glass transition temperature in a soda-lime silicate glass revealed by Raman spectroscopy and its DFT calculations.

To elucidate the atomistic origin of volume relaxation in soda-lime silicate glass annealed below the glass transition temperature (Tg), the experimental and calculated Raman spectra were compared. By decomposing the calculated Raman spectra into specific groups of atoms, the Raman peaks at 800, 950, 1050, 1100, and 1150 cm-1 were attributed to oxygen and silicon in Si-O-Si, non-bridging oxygen in the Q2 unit, bridging oxygen in low-angle Si-O-Si, non-bridging oxygen in the Q4 unit, and bridging oxygen in high-angle Si-O-Si, respectively. Based on these attributions, we found that by decreasing the fictive temperature by annealing below Tg - 70 K, a homogenization reaction Q2 + Q4 → 2Q3 and an increase in average Si-O-Si angle occurred simultaneously. By molecular dynamics simulation, we clarified how the experimentally demonstrated increase in average Si-O-Si angle contributes to volume shrinkage; increasing Si-O-Si angles can expand the space inside the rings, and Na can be inserted into the ring center.

Ultra-high temperature Soret effect in a silicate melt: SiO2 migration to cold side.

The Soret effect, temperature gradient driven diffusion, in silicate melts has been investigated intensively in the earth sciences from the 1980s. The SiO2 component is generally concentrated in the hotter region of silicate melts under a temperature gradient. Here, we report that at ultra-high temperatures above ∼3000 K, SiO2 becomes concentrated in the colder region of the silicate melts under a temperature gradient. The interior of an aluminosilicate glass [63.3SiO2-16.3Al2O3-20.4CaO (mol. %)] was irradiated with a 250 kHz femtosecond laser pulse for local heating. SiO2 migrated to the colder region during irradiation with an 800 pulse (3.2 ms irradiation). The temperature analysis indicated that migration to the colder region occurred above 3060 K. In the non-equilibrium molecular dynamics (NEMD) simulation, SiO2 migrated to the colder region under a temperature gradient, which had an average temperature of 4000 K; this result supports the experimental result. On the other hand, SiO2 exhibited a tendency to migrate to the hotter region at 2400 K in both the NEMD and experimental study. The molar volume calculated by molecular dynamics simulation without a temperature gradient indicates two bends at 1650 and 3250 K under 500 MPa. Therefore, the discontinuous (first order) transition with coexistence of two phases of different composition could be related to the migration of SiO2 to colder region. However, the detailed mechanism has not been elucidated.

Composition-dependent sign inversion of the Soret coefficient of SiO2 in binary borosilicate melts.

Using a laser-induced local-heating experiment combined with temperature analysis, we observed the composition-dependent sign inversion of the Soret coefficient of SiO2 in binary silicate melts, which was successfully explained by a modified Kempers model used for describing the Soret effect in oxide melts. In particular, the diffusion of SiO2 to the cold side under a temperature gradient, which is an anomaly in silicate melts, was observed in the SiO2-poor compositions. The theoretical model indicates that the thermodynamic mixing properties of oxides, partial molar enthalpy of mixing, and partial molar volume are the dominant factors for determining the migration direction of the SiO2 component under a temperature gradient.

Role of mixing thermodynamic properties on the Soret effect.

We demonstrate that the modified Kempers model, a recently developed theoretical model for the Soret effect in oxide melts, is applicable for predicting the composition dependence of the Soret coefficient in three binary molecular liquids with negative enthalpies of mixing. We compared the theoretical and experimental values for water/ethanol, water/methanol, water/ethylene glycol, water/acetone, and benzene/n-heptane mixtures. In water/ethanol, water/methanol, and water/ethylene glycol, which have negative enthalpies of mixing across the entire mole fraction range, the modified Kempers model successfully predicts the sign change of the Soret coefficient with high accuracy, whereas, in water/acetone and benzene/n-heptane, which have composition ranges with positive enthalpies of mixing, it cannot predict the sign change of the Soret coefficient. These results suggest that the model is applicable in composition ranges with negative enthalpies of mixing and provides a framework for predicting and understanding the Soret effect from the equilibrium thermodynamic properties of mixing, such as the partial molar volume, partial molar enthalpy of mixing, and chemical potential.

Osimertinib in poor performance status patients with T790M-positive advanced non-small-cell lung cancer after progression of first- and second-generation EGFR-TKI treatments (NEJ032B).

BACKGROUND: Osimertinib is effective in patients with T790M mutation-positive advanced non-small-cell lung cancer (NSCLC) resistant to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, its effectiveness and safety in patients with poor performance status (PS) are unknown. METHODS: Enrolled patients showed disease progression after treatment with gefitinib, erlotinib, or afatinib; T790M mutation; stage IIIB, IV, or recurrent disease; and PS of 2-4. Osimertinib was orally administered at a dose of 80 mg/day. The primary endpoint of this phase II study (registration, jRCTs061180018) was response rate and the secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate, and safety. RESULTS: Thirty-three patients were enrolled, of which 69.7% and 24.2% had PS of 2 and 3, respectively. One patient was excluded due to protocol violation; in the remaining 32 patients, the response rate was 53.1%; disease control rate was 75.0%; PFS was 5.1 months; and OS was 10.0 months. The most frequent adverse event of grade 3 or higher severity was lymphopenia (12.1%). Interstitial lung disease (ILD) was observed at all grades and at grades 3-5 in 15.2% (5/33) and 6.1% (2/33) of patients, respectively. Treatment-related death due to ILD occurred in one patient. Patients negative for activating EGFR mutations after osimertinib administration had longer median PFS than those positive for these mutations. CONCLUSION: Osimertinib was sufficiently effective in EGFR-TKI-resistant, poor PS patients with T790M mutation-positive advanced NSCLC. Plasma EGFR mutation clearance after TKI treatment could predict the response to EGFR-TKIs.

Structural origin of thermal shrinkage in soda-lime silicate glass below the glass transition temperature: A theoretical investigation by microsecond timescale molecular dynamics simulations.

Microscopic dynamical features in the relaxation of glass structures are one of the most important unsolved problems in condensed matter physics. Although the structural relaxation processes in the vicinity of glass transition temperature are phenomenologically expressed by the Kohlrausch-Williams-Watts function and the relaxation time can be successfully interpreted by Adam-Gibbs theory and/or Narayanaswamy's model, the atomic rearrangement, which is the origin of the volume change, and its driving force have not been elucidated. Using the microsecond time-scale molecular dynamics simulations, this study provides insights to quantitatively determine the origin of the thermal shrinkage below Tg in a soda-lime silicate glass. We found that during annealing below Tg, Na ions penetrate into the six-membered silicate rings, which remedies the acute O-O-O angles of the energetically unstable rings. The ring structure change makes the space to possess the cation inside the rings, but the ring volume is eventually reduced, which results in thermal shrinkage of the soda-lime silica glass. In conclusion, the dynamical structural relaxation due to the cation displacement evokes the overall volume relaxation at low temperature in the glassy material.

Determination of thermodynamic and microscopic origins of the Soret effect in sodium silicate melts: Prediction of sign change of the Soret coefficient.

The Soret effect in silicate melts has attracted attention in earth and material sciences, particularly in glass science and engineering, because a compositional change caused by the Soret effect modifies the material properties of silicate melts. We investigated the Soret effect in an Na2O-SiO2 system, which is the most common representative of silicate melts. Our theoretical approach based on the modified Kempers model and non-equilibrium molecular dynamics simulation was validated for 30Na2O-70SiO2(mol. %). The sign and order of the absolute values of the calculated Soret coefficients were consistent with the experimental values. The positive Soret coefficient of SiO2 in the SiO2-poor composition range was accurately predicted. Previous experimental studies have focused on SiO2-rich compositions, and only the negative sign, indicating SiO2 migration to the hot side, has been observed. In the SiO2-poor composition range, the Q0 structure was dominant and had four Si-O-Na bonds around an SiO4 unit. The Si-O-Na bond had high enthalpic stability and contributed to the large negative enthalpy of SiO2 mixing. According to our model, components with a large negative partial molar enthalpy of mixing will concentrate in the cold region. The microscopic and thermodynamic origins of the sign change in the Soret effect were determined.

Polarization imaging camera with a waveplate array fabricated with a femtosecond laser inside silica glass.

In this study, we demonstrate a polarization imaging camera with a waveplate array of a silica glass fabricated by femtosecond (fs) laser direct writing. To use a waveplate array of silica glass for polarization imaging, non-uniformity of the transmittance and retardance in the waveplates must be considered. Therefore, we used a general method of polarization analysis with system matrices determined experimentally for all the units in the waveplate array. We found that a figure of merit based on the determinant of the system matrix could be applied to improve the accuracy of analysis and the robustness to the retardance dispersion for both the simulated and the fabricated waveplate array.

Comparison of clinical management of young and elderly asthmatics by respiratory specialists and general practitioners.

BACKGROUND: Asthmatic death in the elderly is a serious problem worldwide. Differences in clinical skill between respiratory specialists (RS) and general practitioners (GP) are important in asthma control. The aim of this study was to compare asthma management between RS and GP. METHODS: A cross-sectional survey was carried out in Shimane, Japan, in February 2009 using a questionnaire about patient background, treatment, asthma control test (ACT) and adherence to treatment. We secured the cooperation of 48 clinics (39 private clinics and 9 general hospitals). Asthmatics were divided into the elderly and young groups, and also into the RS and GP groups. RESULTS: Clinical data of 779 patients were available for analysis. Elderly patients constituted 464 (RS group: 192, GP group: 272), while those of the young group were 315 (RS group: 207, GP group: 108). RS prescribed inhaled corticosteroids (ICSs) to their elderly and young patients more than GP. The total ACT score was higher in young RS group than in young GP group, but no such difference was noted in the elderly. Despite more asthma-related symptoms, the ACT showed that elderly GP asthmatics used fewer rescue inhalers than elderly RS. Self-assessment was higher in elderly GP than elderly RS asthmatics. Adherence to therapy was better in elderly patients than young patients. CONCLUSIONS: Elderly asthmatics treated by GPs underestimated the severity of their asthma and asthmatics seen by GPs were undertreated. The results stress the need to engage patients in educational activities, to adhere to guidelines, and to improve the coordination between GP and RS.

Evaluation of a pharmacokineticpharmacodynamic approach using software to optimize the carbapenem antibiotic regimen.

OBJECTIVE: Meropenem (MEPM) and doripenem (DRPM), whose antipseudomonal activity is more potent than that of other carbapenem antimicrobials, were used in the study. Monte Carlo simulation of drug concentrations was performed to develop an administration plan for MEPM and DRPM that takes into account the pharmacokinetics (PK)-pharmacodynamics (PD) of MEPM and DRPM and the renal function of each patient. Drug administration plans were proactively applied to patients with pneumonia to determine the usefulness of the method by assessing treatment efficacy and safety. METHODS: Patients with healthcareassociated pneumonia and an indication for MEPM or DRPM chemotherapy underwent drug administration in accordance with the MEPM and DRPM treatment plan developed by the PK-PD software applications. The primary efficacy endpoints were the clinical and bacteriological efficacy of the drugs agains pneumonia. The safety of the antimicrobials was assessed based on abnormal laboratory findings and the seizure disorders in accordance with the criteria for safety evaluation of antimicrobial agents. RESULTS: This study examined 12 and 11 patients in the MEPM and DRPM group, respectively; however, 3 DRPM patients were excluded due to the administration of anti-methicillin-resistant Staphylococcus aureus drugs after the initiation of DRPM treatment. MEPM and DRPM drug administration was determined to be safe and effective in all patients. CONCLUSIONS: The present results suggest that the Monte Carlo simulation-based PK-PD software is an effective tool for planning individualized antimicrobial chemotherapy with carbapenem in accordance with the PK-PD theory of antimicrobials. It is also possible to propose safe and effective drug administration plans for patients with healthcare-associated pneumonia.

Condensation of Si-rich region inside soda-lime glass by parallel femtosecond laser irradiation.

Local melting and modulation of elemental distributions can be induced inside a glass by focusing femtosecond (fs) laser pulses at high repetition rate (>100 kHz). Using only a single beam of fs laser pulses, the shape of the molten region is ellipsoidal, so the induced elemental distributions are often circular and elongate in the laser propagation direction. In this study, we show that the elongation of the fs laser-induced elemental distributions inside a soda-lime glass could be suppressed by parallel fsing of 250 kHz and 1 kHz fs laser pulses. The thickness of a Si-rich region became about twice thinner than that of a single 250 kHz laser irradiation. Interestingly, the position of the Si-rich region depended on the relative positions between 1 kHz and 250 kHz photoexcited regions. The observation of glass melt during laser exposure showed that the vortex flow of glass melt occurred and it induced the formation of a Si-rich region. Based on the simulation of the transient temperature and viscosity distributions during laser exposure, we temporally interpreted the origin of the vortex flow of glass melt and the mechanism of the formation of the Si-rich region.

Nephrotoxicity induced by piperacillin­tazobactam in late elderly Japanese patients with nursing and healthcare associated pneumonia.

This study aimed to clarify the efficacy, safety, and pharmacokinetics of piperacillin­tazobactam (PIPC­ TAZ) in late elderly Japanese patients. This is the first antimicrobial pilot study in late elderly patients with nursing and healthcare associated pneumonia. After PIPC­TAZ administration, PIPC concentrations in plasma were measured chromatographically and the pharmacokinetic parameters were estimated. Efficacy, safety, and bacteriological evaluations were also carried out. The mean age was 85.0 years old and most of the patients were late elderly. Chest X-rays, body temperature, white blood cell count, and C reactive protein all improved significantly, and a high efficacy ratio of 90.9% was observed. Serious nephrotoxicity was observed in 4 cases (18.2%) after administration of PIPC­TAZ. Creatinine clearance (meanS.D.) measured before PIPC­TAZ therapy was significantly lower in the nephrotoxicity group (32.54.4 mL/min) than in the non-nephrotoxicity group (46.116.7 mL/min), although the ages were not different between the 2 groups. In the pharmacokinetic parameters for PIPC, total clearance was slightly lower in the nephrotoxicity group than in the non-nephrotoxicity group. However, no significant difference was observed in plasma PIPC levels between the 2 groups. In patients with renal impairment, especially with a creatinine clearance of <40 mL/ min, renal impairment was found to be an influencing factor for severe nephrotoxicity following PIPC­TAZ administration. In conclusion, the results suggest that physicians should pay close attention in order to avoid possible toxicity, and that deliberate administration planning and careful follow-up are required in late elderly patients with comprised organ dysfunction.

Modulation of laser induced-cracks inside a LiF single crystal by fs laser irradiation at multiple points.

Crack formations inside a LiF single crystal after femtosecond laser irradiation at multiple points were investigated. In the case of sequential laser irradiation at three points, the propagations of some cracks were prevented by the dislocation bands generated by the previous laser irradiation. On the other hand, in the case of simultaneous laser irradiation at three points with a spatial light modulator, cracks in all the <100> directions from the photoexcited regions were generated clearly, but the length of one crack depended on the distribution of laser irradiation positions. The simulation of elastic dynamics after fs laser irradiation at three points elucidated that the interference of laser induced stress waves depended on the distributions of the irradiation positions. We found that the constructive interference of stress waves at a crack tip should have prevented the crack from propagating further and the tensile stress by destructive interference of stress waves along a crack should have facilitated the propagation of the crack.

White emission of Yb²âº:fluoride glasses efficiently excited with near-UV light.

Various Yb²âº-containing fluoride glasses melting under a reductive atmosphere were prepared. The brightest white light emission was observed for an AlF3-based fluoride glass not containing Hf or Zr. The largest full width at half maximum of the white emission spectra was 202 nm. In addition, incorporation of chloride into the AlF3-based glass enabled efficient excitation with near-ultraviolet light corresponding to a GaN bandgap of 3.4 eV and the maximum internal quantum efficiency of Yb²âº: AlF3-based fluoride glass was 42%.

Shape control of elemental distributions inside a glass by simultaneous femtosecond laser irradiation at multiple spots.

The spatial distributions of elements in a glass can be modulated by irradiation with high repetition rate femtosecond laser pulses. However, the shape of the distribution is restricted to being axially symmetric about the laser beam axis due to the isotropic diffusion of photo-thermal energy. In this study, we describe a method to control the shape of the elemental distribution more flexibly by simultaneous irradiation at multiple spots using a spatial light modulator. The accumulation of thermal energy was induced by focusing 250 kHz fs laser pulses at a single spot inside an alumino-borosilicate glass, and the transient temperature distribution was modulated by focusing 1 kHz laser pulses at four spots in the same glass. The resulting modification was square-shaped. A simulation of the mean diffusion length of molten glass demonstrated that the transient diffusion of elements under heat accumulation and repeated temperature elevation at multiple spots caused the square shape of the distribution.

Efficacy and safety of piperacillin/tazobactam versus biapenem in late elderly patients with nursing- and healthcare-associated pneumonia.

Pneumonia is associated with an extremely high mortality rate in patients of late elderly age. Piperacillin/tazobactam and carbapenems are drugs of first choice for hospitalized patients with potentially resistant bacteria. We compared the efficacy and safety of piperacillin/tazobactam and biapenem. Among elderly patients with nursing- and healthcare-associated pneumonia, we extracted 53 patients treated with piperacillin/tazobactam and 53 patients treated with biapenem who were matched for sex, age, and severity of pneumonia. The average age was more than 80 years; most of the patients were middle- to oldest old in age. Although clinical efficacy was equally good, patients in the piperacillin/tazobactam group achieved significantly faster improvements on chest X-ray and body temperature on day 7. However, in the piperacillin/tazobactam group, nephrotoxicity frequently led to a need for a reduction in the dose or complete discontinuation of treatment. The average age of patients who developed significant nephrotoxicity was high, at 83.2 years. The biapenem group exhibited significantly better continuation of treatment than the piperacillin/tazobactam group. Toxicity profiles were different between the two groups. Hepatic toxicity was significantly higher in the biapenem group, whereas nephrotoxicity was significantly more common in the piperacillin/tazobactam group. Rate of decrease in bacteria was equally good between the two groups. Providing careful follow-up and conducting more detailed examinations, including studies to determine optimal dose and timing of administration, are necessary for the treatment of late elderly patients with numerous underlying diseases and potential organ dysfunctions.

Plasmonically enhanced Faraday effect in metal and ferrite nanoparticles composite precipitated inside glass.

Using femtosecond laser irradiation and subsequent annealing, nanocomposite structures composed of spinel-type ferrimagnetic nanoparticles (NPs) and plasmonic metallic NPs have been formed space-selectively within glass doped with both α-Fe(2)O(3) and Al. The Faraday rotation spectra exhibit a distinct negative peak at around 400 nm, suggesting that the ferrimagnetic Faraday response is enhanced by the localized surface plasmon resonance (LSPR) due to metallic Al NPs. At the interfaces in the nanocomposites, the ferrimagnetism of magnetite NPs is directly coupled with the plasmon in the Al NPs. The control of the resonance wavelength of the magneto-optical peaks, namely, the size of plasmonic NPs has been demonstrated by changing the irradiation or annealing conditions.

Three-dimensional temperature distribution and modification mechanism in glass during ultrafast laser irradiation at high repetition rates.

We experimentally determined the three-dimensional temperature distribution and modification mechanism in a soda-lime-silicate glass under irradiation of ultrafast laser pulses at high repetition rates by analyzing the relationship between the morphology of the modification and ambient temperature. In contrast to previous studies, we consider the temperature dependence of thermophysical properties and the nonlinear effect on the absorbed energy distribution along the beam propagation axis in carrying out analyses. The optical absorptivity evaluated with the temperature distribution is approximately 80% and at most 3.5% smaller than that evaluated by the transmission loss measurement. The temperature distribution and the strain distribution indicate that visco-elastic deformation and material flow play important roles in the laser-induced modification inside a glass.

Localized control of light-matter interactions by using nanoscale asymmetric TiO2.

This paper reports an asymmetry structure-mediated route for highly localized control of light-matter interactions by using tapered TiO(2). We demonstrate for the first time that the growth habit of Ag nanostructures on tapered TiO(2) can be tuned by controllable photolysis. Site-selective anchoring of Ag nanoparticles or nanowires on tapered TiO(2) can be achieved by simply changing the external light. We further show that the obtained tapered TiO(2)-Ag hetero-nanostructures present excellent light-trapping ability over a wide range of wavelengths which is considered to originate from the unique synergistic effects of graded waveguiding and plasmonic light trapping. This improved photon-management capability renders the prepared substrate a very promising candidate for optical sensing application. For this purpose, an enhanced sensitivity for trace detection is confirmed. These findings open up promising avenues for tailoring of light-matter interactions which are of special interest for studying controllable photolysis activation processes and diverse applications such as nanostructure growth, trace detection, photocatalysis and solar cells.