We describe a case of novel use of trametinib in treating arrythmia without concomitant cardiomyopathy. Our patient is a two-year-old female born with Costello syndrome due to heterozygous mutations in the HRAS gene c34 G > T p (G12C). Shortly after birth, she was diagnosed with multifocal atrial tachyarrhythmia. Her imaging studies have shown no hypertrophy or CHD. There was poor arrhythmia control despite triple antiarrhythmic therapy. Trametinib, a MEK1 and MEK2 inhibitor, was used in treating her isolated atrial arrythmia, allowing her to wean off other antiarrhythmics. Other case reports have shown trametinib to benefit certain RASopathy patients with lymphatic abnormalities, hypertrophic cardiomyopathy, and concurrent arrhythmias. This case demonstrates effective treatment of isolated arrhythmia without cardiomyopathy, broadening the potential indications for use of trametinib in certain RASopathy patients.

Tight focusing with very small f-numbers is necessary to achieve the highest at-focus irradiances. However, tight focusing imposes strong demands on precise target positioning in-focus to achieve the highest on-target irradiance. We describe several near-infrared, visible, ultraviolet and soft and hard X-ray diagnostics employed in a ∼1022 W/cm2 laser–plasma experiment. We used nearly 10 J total energy femtosecond laser pulses focused into an approximately 1.3-μm focal spot on 5–20 μm thick stainless-steel targets. We discuss the applicability of these diagnostics to determine the best in-focus target position with approximately 5 μm accuracy (i.e., around half of the short Rayleigh length) and show that several diagnostics (in particular, 3$\omega$ reflection and on-axis hard X-rays) can ensure this accuracy. We demonstrated target positioning within several micrometers from the focus, ensuring over 80% of the ideal peak laser intensity on-target. Our approach is relatively fast (it requires 10–20 laser shots) and does not rely on the coincidence of low-power and high-power focal planes.

Since the exogenous compound tris(hydroxymethyl)aminomethane (Tris) showed a potent chemoattractant activity for Brugia pahangi infective third-stage larvae (L3), it was assumed that, in natural infection to a host, filarial L3 can be expected to recognize an endogenous Tris-related compound. In addition, a few amino acids have been identified as water-soluble attractants for second-stage juveniles of Meloidogyne incognita, a plant parasitic nematode. Therefore, the present study assesses the in vitro chemotactic responses of B. pahangi L3 to Tris-related compounds and amino acids using an agar-plate assay. Among Tris-related compounds, 2-amino-1,3-propanediol (APD) and 2-amino-2-methyl-1,3-propanediol (AMPD) exhibited a potent chemoattractant activity for filarial L3 at a level similar to Tris. Furthermore, arginine (Arg) was identified as a potent attractant for filarial L3 among amino acids. In addition, filarial L3 were attracted to Arg, APD and AMPD in mild alkaline conditions rather than acidic conditions. The chemoattractant activity of the three compounds for filarial L3 was observed in concentrations between 6.3 and 200 mm. This is the first report to demonstrate that Arg, APD and AMPD are potent chemoattractants for B. pahangi L3. Endogenous Arg and APD, in particular, may be involved in the regulation of the chemotactic behaviour of filarial L3 in the infection to a host. The present results will help to elucidate the mechanism of filarial skin-penetrating invasion of a host.

Variability in antidepressant response is due to genetic and environmental factors. Among genetic factors, the ones controlling for availability of the drug at the target site are interesting candidates. Rs6295C/G SNP for 5-HT1A gene (HTR1A) has been found to effect the expression and function of HTR1A In fact rs6295C/G was in strong linkage disequilibrium with other polymorphisms of HTR1A suggesting that those functional effects could be associated with polymorphisms other than the synonymous rs6295C/G. In the present study we examine the possible association of a panel of markers in strong linkage disequilibrium of the HTR1A with SSRI/SNRI response in 137 Japanese major depression sample followed for 6 weeks. We observed the significant association of better response to antidepressant with rs10042486C/C (p<0.0001), rs6295G/G (p<0.0001) and rs1364043T/T (p=0.018) genotype carriers, that is mutant allele homozygote, independently from clinical variables. Furthermore mutant allele homozygote carriers in all these 3 SNPs was associated more solidly with treatment response by various assessment such as HAM-D score change over time (p=0.001), week 2 (p<0.0001), 4(p=0.007), and 6(p=0.048) as well as response rate (p=0.0005) and remission rate (p=0.004).

In conclusion, this is the first study that reports the significant association of antidepressant response with rs10042486C/T and rs1364043G/T variants of HTR1A and also with rs10042486-rs6295-rs1364043 combination. This finding adds an important piece of information for the pathway of detecting the genetics of antidepressant response even if results must be verified on larger samples.

The number of tests performed is an important surveillance indicator. We illustrate this point using HIV surveillance data, focusing on Tokyo and Okinawa, two prefectures with high HIV notification rates in Japan. Restricting to data reported from local public health centres and affiliate centres where testing data are accessible, we assessed HIV surveillance data during 2007–2014, based on the annual HIV notification rate (per 100 000 population), HIV testing rate (per 100 000 population) and proportion testing HIV-positive (positivity). Nationally, testing activity and positivity showed an inverse relationship; in 2008, the testing rate peaked, but positivity was lowest. While notification rates were higher for Tokyo (median = 0.98, range = 0.89–1.33) than Okinawa (median = 0.61, range = 0.42–1.09), Okinawa had slightly higher testing rates (median = 187, range = 158–274) relative to Tokyo (median = 172, range = 163–210). Positivity was substantially lower in Okinawa (median = 0.34%, range = 0.24–0.45%) compared with Tokyo (median = 0.57%, range = 0.46–0.67%). Relative to the national testing rate (median = 85, range = 80–115) and positivity (median = 0.34%, range = 0.28–0.36%), Tokyo had higher positivity, despite more testing. In 2014 in Okinawa, all three indicators increased, providing a strong reason to be concerned as positivity increased despite more testing. Together with other information, accounting for testing and positivity improve interpretation of surveillance data to guide public health assessments.

We report on the formation of shallow junctions with high activation in both n+/p and p+/n Ge junctions using ion implantation and Flash Lamp Annealing (FLA). The shallowest junction depths (Xj) formed for the n+/p and p+/n junctions were 7.6 nm and 6.1 nm with sheet resistances (Rs) of 860 ohms/sq. and 704 ohms/sq., respectively. By reducing knocked-on oxygen during ion implantation in the n+/p junctions, Rs was decreased by between 5% and 15%. The lowest Rs observed was 235 ohms/sq. with a junction depth of 21.5 nm. Hall measurements clearly revealed that knocked-on oxygen degraded phosphorus activation (carrier concentration). In the p+/n Ge junctions, we show that ion implantation damage induced high boron activation. Using this technique, Rs can be reduced from 475 ohms/sq. to 349 ohms/sq. These results indicate that the potential for forming ultra-shallow n+/p and p+/n junctions in the nanometer range in Ge devices using FLA is very high, leading to realistic monolithically-integrated Ge CMOS devices that can take us beyond Si technology.

The overview of the recent results for discovery and investigations of a very exotic phenomenon – optical mirage in the X-ray spectral range – is presented. It was found that the mirage could be created in the form of coherent virtual point source, emerging in the vicinity of the second plasma in two-stage oscillator-amplifier X-ray laser. The X-ray source-mirage, rigidly phased with the initial radiation of generator, occurs only when amplification takes place in the amplifier plasma and leads to the appearance of the interference pattern in the form of concentric rings in the spatial profile of the output X-ray laser beam. The equation describing the emergence of X-ray mirage was found, numerical solution of which shows that its formation is similar to that of the optical mirages observed at propagation of light rays through an inhomogeneously heated air. Obtained results have already demonstrated novel comprehension into the physical nature of amplification of X-ray radiation, opening additional opportunities for X-ray interferometry, holography, and other applications, which require multiple rigidly phased sources of coherent radiation.

This paper describes an overview of our recent discovery – clear demonstration that LiF crystals can be efficiently used as a high-performance neutron imaging detector based on optically stimulated luminescence of color centers generated by neutron irradiation. It is shown that the neutron images we have obtained are almost free from granular noise, have a spatial resolution of ${\sim}5.4~{\rm\mu}\text{m}$ and a linear response with a dynamic range of at least $10^{3}$. The high contrast and good sensitivity of LiF crystals allow us to distinguish two holes with less than 2% transmittance difference. We propose to use such detectors in areas where high spatial resolution with high image gradation resolution is needed, including diagnostics of different plasma sources such as laser and z-pinch produced plasmas.

This paper solves the known problem of elimination of unnecessary internal element construction as well as variable elimination in XML processing with (a subset of) XQuery without ignoring the issues of document order. The semantics of XQuery is context sensitive and requires preservation of document order. In this paper, we propose, as far as we are aware, the first XQuery fusion that can deal with both the document order and the context of XQuery expressions. More specifically, we carefully design a context representation of XQuery expressions based on the Dewey order encoding, develop a context-preserving XQuery fusion for ordered trees by static emulation of the XML store, and prove that our fusion is correct. Our XQuery fusion has been implemented, and all the examples in this paper have passed through the system.

We previously revealed that Japanese encephalitis virus (JEV) seroprevalence was 4·5% in pigs on Ishigaki Island from 2005 to 2007. However, a partial E gene sequence (151 bp) of the JEV genome (JEV/sw/Ishigaki/1/2005) was detected in one pig. Phylogenetic analysis showed that JEV/sw/Ishigaki/1/2005 belonged to genotype III and to the same lineages isolated in Taiwan from 2006 to 2008. Serum samples were collected from 128 pigs on Ishigaki from 2009 to 2010, 24 wild boars on Ishigaki from 2008 to 2010, and 117 wild boars on Iriomote Island from 2008 to 2010. Four (3·1%) pigs on Ishigaki were positive for JEV antibody, but all wild boars on the island were negative. Fifty-two (44·4%) wild boars on Iriomote were positive for JEV antibody, in contrast to a seroprevalence of 3·7% in 2000 and 2004. JEV on Iriomote and/or in Taiwan might be related to transmission on Ishigaki.

It is shown that various spectroscopic methods based on measurements of X-ray spectra radiated from cluster targets can be used for estimation of the destruction degree of clusters by laser prepulses. These methods allow insight to be gained regarding the important issue of preservation of the dense cluster core at the moment of the arrival of the main laser pulse. In addition, they can be used for quantitative estimation of the size of the undestroyed parts of the clusters and also for measuring the temperature and density of the preplasmas produced by the laser prepulses.

Results of our experimental investigation on the ozone zero phenomenon suggested us the importance of the electrode surface condition. This means that the main cause of the phenomenon, that is, temporal decrease of ozone concentration at the outlet of DBD type ozone generator and the recovery characteristics from the phenomenon are considered as the surface reaction process, which are influenced strongly by the surface condition. The surface condition is never constant during the ozone generation and varies gradually or remarkably with time depending on the experimental conditions. Therefore we have been continued to make clear the cause of the phenomenon, for example, the reproducibility of the phenomenon, using new electrodes and together with the surface analysis technique etc. In this paper, we describe on the above results and discussion.

We have prepared a CrO2 thin film by chemical vapor deposition from a Cr8O21 precursor and studied the bulk and surface physical properties. The CrO2 thin film is grown on TiO2(100) substrate by heating precursor and TiO2 (100) substrate together in a sealed quartz tube. The prepared film is found from x-ray diffraction analysis to be an (100)-oriented single phase. The magnetization and resistivity measurements indicate that the film is a ferromagnetic metal with a Curie temperature of about 400 K. Cr 3s core-level and valence band photoelectron spectroscopy spectra reveal the presence of a metallic CrO2 in the surface region of the film. Our work indicates that preparation from a Cr8O21 precursor in a closed system is promising for obtaining a CrO2 thin film with the metallic surface.

A histopathological study was performed to clarify the characteristics of granuloma formation and liver fibrosis in Schistosoma mekongi infection in comparison with S. japonicum infection. Mice were exposed to S. mekongi (Laotian strain) and S. japonicum (Japanese strain) cercariae, and were dissected at 6, 8, 12, 16, and 20 weeks post-exposure. In the liver, granulomas in S. mekongi infection were cellular, initially organized with foam cells, and continuously appeared in the intralobular area, while granulomas in S. japonicum infection were fibrous and did not continuously appear in the intralobular area. Portal fibrosis was not seen in S. mekongi infection, but was commonly seen in S. japonicum infection in the later weeks. Granulomas in the small intestine were seen mainly in the submucosa with foam cells in S. mekongi infection and without foam cells in S. japonicum infection. The lung granulomas contained mainly histiocytes in both S. mekongi and S. japonicum infection. The absence of portal fibrosis in S. mekongi infection allows schistosome eggs to infiltrate into the intralobular area continuously, which can be what lies behind the ultrasonographic differences; the echogenic network pattern as was seen in S. japonicum infection, has not been noted in S. mekongi infection.