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Abstract Precordial Doppler ultrasound technology can be utilized to confirm correct peripheral intravenous vascular (PIV) access in children during surgery. This study aimed to determine the minimally required dose of normal saline (NS) for confirming correct PIV access. Healthy children were randomly allocated to receive a 0.1 mL/kg, 0.3 mL/kg, or 0.5 mL/kg dose of NS injected via PIV access. Two independent raters judged the change in the recorded precordial Doppler sound test (S-test) before and after NS injection. Typically, rapid injection of NS increased the pitch of the heartbeat as the injection volume increased. Changes in blood flow velocity test (V-test) results were evaluated using a cut-off value of 1 cm/s. Both in the S- and V-tests, the detection rate of correct PIV access was lower with 0.1 mL/kg NS than with 0.3 mL/kg or 0.5 mL/kg. Logistic regression analysis showed that the positive results in both the S- and V-tests were significantly decreased with a 0.1 mL/kg NS; no significant difference was observed with a 0.3 mL/kg NS (reference dose: 0.5 mL/kg). These results suggest 0.3 mL/kg is the minimally required dose of NS for confirming correct PIV access. This study is registered with the University Hospital Medical Information Network (UMIN000041330).

We developed an electron gun system capable of delivering high brightness beams to drive soft x-ray free-electron lasers (SXFEL). We modified the conventional radio-frequency (rf) gun concept by using a 50-kV gun with a gridded thermionic cathode connected with a 238-MHz acceleration cavity. We achieved a low target emittance by applying the following two methods: (1) to obtain a parallel beam after the control grid, we optimized the grid voltage to compensate for the electric potential distortion near the grid (i.e., the lens effect); and (2) to avoid emittance growth due to the space charge effect at low energy regions, the 50-kV gun was connected to a 238-MHz rf cavity with a minimum distance, which immediately accelerated the beam energy to 500 keV. We built a gun test stand to verify the high beam performance, i.e., a normalized emittance of less than 4 mm mrad with a bunch charge of 1 nC and a pulse length shorter than 0.7 ns, as predicted by cst and parmela codes. Our proof-of-performance experiments demonstrated that a projection emittance of 1.7 mm mrad was obtained as a core part, representing 60% of all extracted electrons and the measured emittance agreed well with the simulation value of 2.0 mm mrad. This paper presents an overview of the electron gun system and our proof-of-performance experimental results.

The parallel operation of multiple beam lines is an important means to expand the opportunity of user experiments at x-ray free-electron laser (XFEL) facilities. At SPring-8 Angstrom free-electron laser (SACLA), the multi-beam-line operation had been tested using two beam lines, but transverse coherent synchrotron radiation (CSR) effects at a dogleg beam transport severely limited the laser performance. To suppress the CSR effects, a new beam optics based on two double bend achromat (DBA) structures was introduced for the dogleg. After the replacement of the beam optics, high peak current bunches of more than 10 kA are now stably transported through the dogleg and the laser pulse output is increased by a factor of 2–3. In the multi-beam-line operation of SACLA, the electron beam parameters, such as the beam energy and peak current, can be adjusted independently for each beam line. Thus the laser output can be optimized and wide spectral tunability is ensured for all beam lines.

A low-emittance thermionic-gun-based injector was developed for the x-ray free-electron laser (XFEL) facility known as the SPring-8 angstrom compact free-electron laser (SACLA). The thermionic-gun-based system has the advantages of maintainability, reliability, and stability over a photocathode radio-frequency (rf) gun because of its robust thermionic cathode. The basic performance of the injector prototype was confirmed at the SPring-8 compact self-amplified spontaneous emission source (SCSS) test accelerator, where stable FEL generation in an extreme ultraviolet wavelength range was demonstrated. The essential XFEL innovation is the achievement of a constant beam peak current of 3–4 kA, which is 10 times higher than that generated by the SCSS test accelerator, while maintaining a normalized-slice emittance below 1 mm mrad. Thus, the following five modifications were applied to the SACLA injector: (i) a nonlinear energy chirp correction; (ii) the optimization of the rf acceleration frequency; (iii) rf system stabilization; (iv) nondestructive beam monitoring; and (v) a geomagnetic field correction. The SACLA injector successfully achieved the target beam performance, which shows that a thermionic-gun-based injector is applicable to an XFEL accelerator system. This paper gives an overview of the SACLA injector and describes the physical and technical details, together with the electron beam performance obtained in the beam commissioning.

An x-ray free-electron laser (XFEL), SACLA, designed to open up new science, was constructed for generating coherent x rays with a peak power of more than 10 GW and a very short pulse of below 30 fs. This feature demands a very highly short-term temporal stability of less than 50 fs to the acceleration rf field of SACLA. For this reason, we developed a timing and low-level rf (LLRF) system for SACLA based on that of the SPring8 compact SASE source (SCSS) test accelerator for verifying the feasibility of an XFEL. The performance of the system using the in-phase and quadrature rf manipulation method was improved from SCSS’s system. Since the facility length of SACLA is 700 m, which is 10 times longer than that of the SCSS test accelerator, a phase-stabilized optical-fiber system designed to transmit time standard rf signals with low loss was also developed and deployed. This optical-fiber system equips fiber optical-length feedback control in order to mitigate environmental effects, such as temperature and humidity changes. On the other hand, the demanded maximum rf temporal stability is less than 50 fs, which is almost 10 times smaller than that of the SCSS test accelerator. Hence, reducing electric noise and increasing the temperature stability around timing and LLRF instruments were necessary and realized with a very low-noise power supply and a hemathermal 19-inch enclosure. The short-term temporal performance of the timing LLRF system finally attained a temporal stability of less than 13.6 fs in rms measured by a beam arrival-time measurement. This stability greatly helps to achieve the stable x-ray lasing of SACLA for routine operation during user experiments.

The parallel operation of plural undulator beam lines is an important means of improving the efficiency and usability of x-ray free-electron laser facilities. After the installation of a second undulator beam line (BL2) at SPring-8 Angstrom compact free-electron laser (SACLA), pulse-by-pulse switching between two beam lines was tested using kicker and dc twin-septum magnets. To maintain a compact size, all undulator beam lines at SACLA are designed to be placed within the same undulator hall located downstream of the accelerator. In order to ensure broad tunability of the laser wavelength, the electron bunches are accelerated to different beam energies optimized for the wavelengths of each beam line. In the demonstration, the 30 Hz electron beam was alternately deflected to two beam lines and simultaneous lasing was achieved with 15 Hz at each beam line. Since the electron beam was deflected twice by 3° in a dogleg to BL2, the coherent synchrotron radiation (CSR) effects became non-negligible. Currently in a wavelength range of 4–10 keV, a laser pulse energy of 100–150 μJ can be obtained with a reduced peak current of around 1 kA by alleviating the CSR effects. This paper reports the results and operational issues related to the multi-beam-line operation of SACLA.

To meet the demand from the growing number of user experiments, multi-beam-line operation with a wide spectral range is seriously considered in x-ray free-electron laser facilities. In a conventional design, the beam line of low photon energies branches off from the middle of the accelerator to take out low energy electron beams. Here in this paper, a novel method is proposed to deliver bunch-to-bunch energy changed electron beams at the end of the accelerator. Since all accelerator components are operated in steady state, this method enables quasisimultaneous operation of multi-beam-line in the same undulator hall without degrading the stability and performance of the electron beam.

We achieved stable operation of a free-electron laser (FEL) based on the self-amplified spontaneous-emission (SASE) scheme at the SPring-8 Compact SASE Source (SCSS) test accelerator in the extremely ultraviolet region. Saturation of the SASE FEL power has been achieved at wavelengths ranging from 50 to 60 nm. The pulse energy has reached ∼30 μJ at 60 nm. The observed fluctuation of the pulse energy is about 10% (standard deviation) for several hours, which agrees with the expectation from the SASE theory showing the stable operation of the accelerator. The SASE FEL has been routinely operated to provide photon beams for user experiments over a period of a few weeks. Analysis on the experimental data gave the normalized-slice emittance at the lasing part is around 0.7π mm mrad. This result indicates that the normalized-slice emittance of the initial electron beam, 0.6π mm mrad in a 90% core part, is kept almost unchanged after the bunch compression process with a compression factor of approximately 300. The success of the SCSS test accelerator strongly encourages the realization of a compact XFEL source.

Pancreatic ductal adenocarcinoma (PDAC) develops via an accumulation of various gene mutations. The mechanism underlying the mutations in PDAC development, however, is not fully understood. Recent insight into the close association between the mutation pattern of various cancers and specific mutagens led us to investigate the possible involvement of activation-induced cytidine deaminase (AID), a DNA editing enzyme, in pancreatic tumorigenesis. Our immunohistochemical findings revealed AID protein expression in human acinar ductal metaplasia, pancreatic intraepithelial neoplasia, and PDAC. Both the amount and intensity of the AID protein expression increased with the progression from precancerous to cancerous lesions in human PDAC tissues. To further assess the significance of ectopic epithelial AID expression in pancreatic tumorigenesis, we analyzed the phenotype of AID transgenic (AID Tg) mice. Consistent with our hypothesis that AID is involved in the mechanism of the mutations underlying pancreatic tumorigenesis, we found precancerous lesions developing in the pancreas of AID Tg mice. Using deep sequencing, we also detected Kras and c-Myc mutations in our analysis of the whole pancreas of AID Tg mice. In addition, Sanger sequencing confirmed the presence of Kras, c-Myc, and Smad4 mutations, with the typical mutational footprint of AID in precancerous lesions in AID Tg mice separated by laser capture microdissection. Taken together, our findings suggest that AID contributes to the development of pancreatic precancerous lesions by inducing tumor-related gene mutations. Our new mouse model without intentional manipulation of specific tumor-related genes provides a powerful system for analyzing the mutations involved in PDAC. [ABSTRACT FROM AUTHOR]