Preoperative evaluation of pleural adhesions with dynamic chest radiography: a retrospective study of 146 patients with lung cancer.

AIM: To assess the utility of dynamic chest radiography (DCR) during the preoperative evaluation of pleural adhesions. MATERIALS AND METHODS: Sequential chest radiographs of 146 patients with lung cancer were acquired during forced respiration using a DCR system. The presence of pleural adhesions and their grades were determined by retrospective surgery video assessment (absent: 121, present: 25). The maximum inspiration to expiration lung area ratio was used as an index for air intake volume. A ratio of ≥0.65 was regarded as insufficient respiration. Two radiologists assessed the images for pleural adhesions based on motion findings. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were compared for each adhesion grade and patient group (patients with sufficient/insufficient respiration). Pearson's chi-squared test compared the group. Statistical significance was set at p<0.05. RESULTS: DCR correctly identified 22/25 patients with pleural adhesions, with 20 false-positive results (sensitivity, 88%; specificity, 83.5%; PPV, 52.4%; NPV, 97.12%). Although the diagnostic performances for the various adhesion grades were similar, specificity in patients with sufficient respiration increased to 93.9% (31/33), identifying all cases except for those with loose adhesions. CONCLUSIONS: DCR images revealed restricted and/or distorted motions in lung structures and structural tension in patients with pleural adhesions. DCR could be a useful technique for routine preoperative evaluation of pleural adhesions. Further development of computerised methods can assist in the quantitative assessment of abnormal motion findings.

Asteroseismic detection of latitudinal differential rotation in 13 Sun-like stars.

The differentially rotating outer layers of stars are thought to play a role in driving their magnetic activity, but the underlying mechanisms that generate and sustain differential rotation are poorly understood. We report the measurement using asteroseismology of latitudinal differential rotation in the convection zones of 40 Sun-like stars. For the most significant detections, the stars' equators rotate approximately twice as fast as their midlatitudes. The latitudinal shear inferred from asteroseismology is much larger than predictions from numerical simulations.

Characteristics of adverse drug reactions in a vemurafenib early post-marketing phase vigilance study in Japan

Background. Post-approval research or monitoring is important to determine real-world safety of new products; however, evidence is scant for vemurafenib in Japanese patients. In Japan, a unique system is officially obligated to investigate post-approval safety. Here we report the first adverse drug reaction (ADR) data from vemurafenib-treated Japanese patients with metastatic melanoma. Data were collected in an early post-marketing phase vigilance (EPPV) study. Methods. ADRs were events for which a causal relationship with vemurafenib could not be ruled out or was unknown. ADR data were collected for patients treated with vemurafenib (960 mg bid) between 26 February and 25 August 2015. Results. Among 95 patients, 46 patients had 118 ADRs (24 serious ADRs in 13 patients). The most common serious ADRs were hypersensitivity (n = 1; 3 events), arthralgia (n = 2; 2 events), pyrexia (n = 2; 2 events) and drug eruption (n = 2; 2 events). Seven patients had serious skin disorders or hypersensitivity, six of whom had prior anti-programmed cell death-1 (PD-1) antibodies 5-35 days before starting vemurafenib. ADR reports of serious skin disorders appeared to be collected more rapidly than previously reported. Cutaneous squamous cell carcinoma developed in only one patient. Conclusions. EPPV in Japanese vemurafenib-treated patients identified no new safety signals. The most serious skin and hypersensitivity ADRs occurred in patients with prior anti-PD-1 exposure. Cutaneous squamous cell carcinoma appeared to be rare in Japanese patients. Further research is needed to clarify whether prior treatment with anti-PD-1 agents or racial differences affect the characteristic profile of cutaneous ADRs in Japanese patients (AU)

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Characteristics of adverse drug reactions in a vemurafenib early post-marketing phase vigilance study in Japan.

BACKGROUND: Post-approval research or monitoring is important to determine real-world safety of new products; however, evidence is scant for vemurafenib in Japanese patients. In Japan, a unique system is officially obligated to investigate post-approval safety. Here we report the first adverse drug reaction (ADR) data from vemurafenib-treated Japanese patients with metastatic melanoma. Data were collected in an early post-marketing phase vigilance (EPPV) study. METHODS: ADRs were events for which a causal relationship with vemurafenib could not be ruled out or was unknown. ADR data were collected for patients treated with vemurafenib (960 mg bid) between 26 February and 25 August 2015. RESULTS: Among 95 patients, 46 patients had 118 ADRs (24 serious ADRs in 13 patients). The most common serious ADRs were hypersensitivity (n = 1; 3 events), arthralgia (n = 2; 2 events), pyrexia (n = 2; 2 events) and drug eruption (n = 2; 2 events). Seven patients had serious skin disorders or hypersensitivity, six of whom had prior anti-programmed cell death-1 (PD-1) antibodies 5-35 days before starting vemurafenib. ADR reports of serious skin disorders appeared to be collected more rapidly than previously reported. Cutaneous squamous cell carcinoma developed in only one patient. CONCLUSIONS: EPPV in Japanese vemurafenib-treated patients identified no new safety signals. The most serious skin and hypersensitivity ADRs occurred in patients with prior anti-PD-1 exposure. Cutaneous squamous cell carcinoma appeared to be rare in Japanese patients. Further research is needed to clarify whether prior treatment with anti-PD-1 agents or racial differences affect the characteristic profile of cutaneous ADRs in Japanese patients.

Heat-Treatment-Induced Switching of Magnetic States in the Doped Polar Semiconductor Ge1-xMnxTe.

Cross-control of a material property - manipulation of a physical quantity (e.g., magnetisation) by a nonconjugate field (e.g., electrical field) - is a challenge in fundamental science and also important for technological device applications. It has been demonstrated that magnetic properties can be controlled by electrical and optical stimuli in various magnets. Here we find that heat-treatment allows the control over two competing magnetic phases in the Mn-doped polar semiconductor GeTe. The onset temperatures Tc of ferromagnetism vary at low Mn concentrations by a factor of five to six with a maximum Tc ≈ 180 K, depending on the selected phase. Analyses in terms of synchrotron x-ray diffraction and energy dispersive x-ray spectroscopy indicate a possible segregation of the Mn ions, which is responsible for the high-Tc phase. More importantly, we demonstrate that the two states can be switched back and forth repeatedly from either phase by changing the heat-treatment of a sample, thereby confirming magnetic phase-change-memory functionality.

Contemporary evolution of host plant range expansion in an introduced herbivorous beetle Ophraella communa.

Host range expansion of herbivorous insects is a key event in ecological speciation and insect pest management. However, the mechanistic processes are relatively unknown because it is difficult to observe the ongoing host range expansion in natural population. In this study, we focused on the ongoing host range expansion in introduced populations of the ragweed leaf beetle, Ophraella communa, to estimate the evolutionary process of host plant range expansion of a herbivorous insect. In the native range of North America, O. communa does not utilize Ambrosia trifida, as a host plant, but this plant is extensively utilized in the beetle's introduced range. Larval performance and adult preference experiments demonstrated that native O. communa beetles show better survival on host plant individuals from introduced plant populations than those from native plant populations and they also oviposit on the introduced plant, but not on the native plant. Introduced O. communa beetles showed significantly higher performance on and preference for both introduced and native A. trifida plants, when compared with native O. communa. These results indicate the contemporary evolution of host plant range expansion of introduced O. communa and suggest that the evolutionary change of both the host plant and the herbivorous insect involved in the host range expansion.

Control of parental investment changes plastically over time with residual reproductive value.

Evolutionary conflict between parents and offspring over parental resource investment is a significant selective force on the traits of both parents and offspring. Empirical studies have shown that for some species, the amount of parental investment is controlled by the parents, whereas in other species, it is controlled by the offspring. The main difference between these two strategies is the residual reproductive value of the parents or opportunities for future reproduction. Therefore, this could explain the patterns of control of parental investment at the species level. However, the residual reproductive value of the parents will change during their lifetime; therefore, parental influence on the amount of investment can be expected to change plastically. Here, we investigated control of parental investment when parents were young and had a high residual reproductive value, compared to when they were old and had a low residual reproductive value using a cross-fostering experiment in the burying beetle Nicrophorus quadripunctatus. We found that parents exert greater control over parental investment when they are young, but parental control is weakened as the parents age. Our results demonstrate that control of parental investment is not fixed, but changes plastically during the parent's lifetime.

Ferroelectric-like metallic state in electron doped BaTiO3.

We report that a ferroelectric-like metallic state with reduced anisotropy of polarization is created by the doping of conduction electrons into BaTiO3, on the bases of x-ray/electron diffraction and infrared spectroscopic experiments. The crystal structure is heterogeneous in nanometer-scale, as enabled by the reduced polarization anisotropy. The enhanced infrared intensity of soft phonon along with the resistivity reduction suggests the presence of unusual electron-phonon coupling, which may be responsible for the emergent ferroelectric structure compatible with metallic state.

Effects of DSP-8658, a novel selective peroxisome proliferator-activated receptors a/γ modulator, on adipogenesis and glucose metabolism in diabetic obese mice.

AIMS/INTRODUCTION: Peroxisome proliferator-activated receptors (PPARs) play a key regulating role in homeostasis. In this study, we investigated the effects of DSP-8658, a novel selective PPARa/γ modulator, on adipogenesis and glucose metabolism in diabetic obese mice and compared these effects to those of pioglitazone, a PPARγ full agonist. MATERIALS AND METHODS: DSP-8658 functional activity was assessed by PPARγ-target genes expression in adipose 3T3-L1 cells and its anti-diabetic efficacy evaluated in db/db mice. The effects of DSP-8658 on adipogenesis were investigated diet induced obese (DIO) KK-A(y) mice. RESULTS: DSP-8658 reduced the expression of PPARγ-target gene 11 beta hydroxysteroid dehydrogenase type 1 with an EC50 value 2.1-fold that of pioglitazone and 28.4-fold that of rosiglitazone. On the other hand, DSP-8658 increased the expression of fatty acid binding protein 4 and glycerol kinase genes with EC50 values 33-fold and >15-fold those of pioglitazone and 163-fold and >38-fold those of rosiglitazone, respectively. In db/db mice, DSP-8658, like pioglitazone, decreased blood glucose, HbA1c, and plasma triglyceride levels and increased plasma insulin concentration and pancreatic insulin contents. In DIO KK-A(y) mice, DSP-8658, unlike pioglitazone, decreased subcutaneous adipose tissue weight and mean adipocyte size. However, both DSP-8658 and pioglitazone improved blood glucose and HbA1c levels with similar efficacy. Although DSP-8658 did not change the expression levels of fatty acid transport protein 1 and glycerol kinase genes in subcutaneous adipose tissue of KK-A(y) mice, pioglitazone increased these gene expression levels. CONCLUSION: Unlike PPARγ full agonists, DSP-8658 ameliorates blood glucose without increasing adipogenesis in diabetic obesity mice.

Asynchronous hatching in the burying beetle, Nicrophorus quadripunctatus, maxmizes parental fitness.

Life history theory predicts that natural selection favours parents who balance investment across offspring to maximize fitness. Theoretical studies have shown that the optimal level of parental investment from the offspring's perspective exceeds that of its parents, and the disparity between the two generates evolutionary conflict for the allocation of parental investment. In various species, the offspring hatch asynchronously. The age hierarchy of the offspring usually establishes competitive asymmetries within the brood and determines the allocation of parental investment among offspring. However, it is not clear whether the allocation of parental investment determined by hatching pattern is optimal for parent or offspring. Here, we manipulated the hatching pattern of the burying beetle Nicrophorus quadripunctatus to demonstrate the influence of hatching pattern on the allocation of parental investment. We found that the total weight of a brood was largest in the group that mimicked the natural hatching pattern, with the offspring skewed towards early hatchers. This increases parental fitness. However, hatching patterns with more later hatchers had heavier individual offspring weights, which increases offspring fitness, but this hatching pattern is not observed in the wild. Thus, our study suggests that the natural hatching pattern optimizes parental fitness, rather than offspring fitness.

Hydrogen-induced structural transformation of AuCu nanoalloys probed by synchrotron X-ray diffraction techniques.

In situ X-ray diffraction measurements reveal that the transformation of a AuCu nanoalloy from a face-centered-cubic to an L10 structure is accelerated under a hydrogen atmosphere. The structural transformation rate for the AuCu nanoalloy under hydrogen above 433 K was found to be 100 times faster than that in a vacuum, which is the first quantitative observation of hydrogen-induced ordering of nanoalloys.

Spin and orbital contributions to magnetically ordered moments in 5d layered perovskite Sr2IrO4.

The ratio of orbital (L) and spin (S) contributions to the magnetically ordered moments of a 5d transition metal oxide, Sr2IrO4 was evaluated by nonresonant magnetic x-ray diffraction. We applied an improved experimental setting that minimized the experimental error, in which we varied only the linear polarization of incident x ray at a fixed scattering angle. Strong polarization dependence of the intensity of magnetic diffraction was observed, from which we conclude that the ordered moments contain substantial contribution from the orbital degree of freedom with the ratio of /∼5.0, evidencing the pronounced effect of spin-orbit coupling. The obtained ratio is close to, but slightly larger than the expected value for the ideal J(eff) = 1/2 moment of a spin-orbital Mott insulator, ||/|| = 4, which cannot be accounted for by the redistribution of orbital components within the t(2g) bands associated with the elongation of the IrO6 octahedra.

Saliva collection by using filter paper for measuring cortisol levels in dogs.

Four experiments were conducted to evaluate the accuracy and reliability of noninvasive evaluation of cortisol in saliva of dogs. In experiment 1, we measured the cortisol concentration in the filter paper on which 250-µL cortisol solutions had been quantitatively pipetted and in filter papers dipped in cortisol solution. In experiment 2, we collected the blood and saliva of dogs 3 times at 30-min intervals and compared the cortisol concentrations to examine whether the dynamics of cortisol in the blood and saliva are similar. The results of experiments 1 and 2 showed that the cortisol concentration can be quantitatively measured with this method and that the dynamics of cortisol concentration in the plasma and saliva collected by using filter paper are not different (P = 0.14 for experiment 1 and P = 0.51 for experiment 2). In experiment 3, to investigate the factors related to inducing stress in dogs by using the filter-paper method of collecting saliva, we compared the cortisol concentrations at 0 and 30 min after collecting the saliva of pet dogs. The dog owners completed a survey on their dogs, providing basic information and reporting the collection of their dog's saliva. We found that the cortisol concentrations increased significantly in dogs whose owners spent >2 min collecting saliva (P = 0.005), suggesting that prompt collection of saliva is necessary for accurate assessment of cortisol without induction of a stress response. In addition, the cortisol concentrations increased significantly in dogs whose teeth were not regularly brushed (P = 0.04), suggesting that regular teeth brushing mitigates the effect of the collection process on cortisol concentrations in the saliva, with minimal stress to the dogs. In experiment 4, we measured cortisol concentrations in pet dogs accustomed to having their teeth brushed by their owners, before and after interaction with their owners, to assess whether brushing induces stress in dogs. We detected that the cortisol concentrations significantly decreased after human-dog interaction (P = 0.008), suggesting that this method does not induce stress in dogs. Our study indicates that the method of saliva collection by using filter paper is effective in measuring the cortisol concentrations to evaluate stress, although certain steps are required to enhance accuracy.

RISING beamline (BL28XU) for rechargeable battery analysis.

The newly installed BL28XU beamline at SPring-8 is dedicated to in situ structural and electronic analysis of rechargeable batteries. It supports the time range (1 ms to 100 s) and spatial range (1 µm to 1 mm) needed for battery analysis. Electrochemical apparatus for battery charging and discharging are available in experimental hutches and in a preparation room. Battery analysis can be carried out efficiently and effectively using X-ray diffraction, X-ray absorption fine-structure analysis and hard X-ray photoelectron spectroscopy. Here, the design and performance of the beamline are described, and preliminary results are presented.

Fasudil, a rho kinase inhibitor, limits motor neuron loss in experimental models of amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with no effective treatment. Fasudil hydrochloride (fasudil), a potent rho kinase (ROCK) inhibitor, is useful for the treatment of ischaemic diseases. In previous reports, fasudil improved pathology in mouse models of Alzheimer's disease and spinal muscular atrophy, but there is no evidence in that it can affect ALS. We therefore investigated its effects on experimental models of ALS. EXPERIMENTAL APPROACH: In mice motor neuron (NSC34) cells, the neuroprotective effect of hydroxyfasudil (M3), an active metabolite of fasudil, and its mechanism were evaluated. Moreover, the effects of fasudil, 30 and 100 mg·kg(-1), administered via drinking water to mutant superoxide dismutase 1 (SOD1(G93A)) mice were tested by measuring motor performance, survival time and histological changes, and its mechanism investigated. KEY RESULTS: M3 prevented motor neuron cell death induced by SOD1(G93A). Furthermore, M3 suppressed both the increase in ROCK activity and phosphorylated phosphatase and tensin homologue deleted on chromosome 10 (PTEN), and the reduction in phosphorylated Akt induced by SOD1(G93A). These effects of M3 were attenuated by treatment with a PI3K inhibitor (LY294002). Moreover, fasudil slowed disease progression, increased survival time and reduced motor neuron loss, in SOD1(G93A) mice. Fasudil also attenuated the increase in ROCK activity and PTEN, and the reduction in Akt in SOD1(G93A) mice. CONCLUSIONS AND IMPLICATIONS: These findings indicate that fasudil may be effective at suppressing motor neuron degeneration and symptom progression in ALS. Hence, fasudil may have potential as a therapeutic agent for ALS treatment.

Electronic phase transition and an anomalous ordered phase in Ba2Ti13O22 with 3d1 ions on a triangle-based lattice.

We found that Ba(2)Ti(13)O(22) with Ti(3+) (3d(1)) ions on a triangle-based lattice exhibits a phase transition at T(c)~200 K, below which the increase of electrical resistivity and decrease of magnetic susceptibility were observed. Transmission electron microscopy and optical reflectivity measurements indicate that the low-temperature phase of the present compound shares characteristics in common with a charge-density-wave state with remnant carriers, although a commensurate wave vector of the modulation and a linear temperature dependence of the magnetic susceptibility below T(c) suggest an exotic ordered state.

A-type antiferro-orbital ordering with I4(1)/a symmetry and geometrical frustration in the spinel vanadate MgV2O4.

We conduct a detailed structural analysis of the S=1 pyrochlore antiferromagnet MgV2O4, which exhibits an antiferromagnetic ordering marginally at TN=40 K, triggered by a structural transition from cubic to tetragonal symmetry at TS=62 K, using high resolution synchrotron x-ray diffraction and convergent beam electron diffraction. We reveal that the tetragonal phase below TS has the symmetry of I4(1)/a and that the distortion pattern of VO6 octahedra is consistent with A-type antiferro-orbital ordering with alternating stacking of layers with yz/xy orbital chains and zx/xy orbital chains along the tetragonal c axis. This implies that an anisotropic coupling of V moments produced by the orbital ordering below TS primarily brings about the antiferromagnetic ordering.

Inflammatory mechanisms of ventilator-induced lung injury: a time to stop and think?

Ventilator-induced lung injury (VILI) is the phenomenon by which mechanical ventilation exacerbates lung injury in critically ill patients. It is particularly relevant for those suffering from acute respiratory distress syndrome, in which the iatrogenic injury caused by VILI contributes to their high mortality. The innate immune system is widely accepted to play an important role during VILI. However, it is our belief that the identification of inflammatory mediators that are crucial during VILI, and thus may make useful therapeutic targets, has become obscured by the wide variety of pre-clinical animal models of VILI reported in the literature. We aim here to summarise some of our work addressing this issue over the last 10 years, and thus, we hope, make interpretation of a convoluted field a little clearer.