Demonstration of an intense lithium beam for forward-directed pulsed neutron generation.

As an alternative to research nuclear reactors, a compact accelerator-driven neutron generator that uses a lithium beam driver could be a promising candidate since it produces almost no undesired radiation. However, providing an intense lithium-ion beam has been difficult, and it has been thought that the practical application of such a device would be impossible. The most critical problem of insufficient ion fluxes has been solved by applying a direct plasma injection scheme. In this scheme, a pulsed high-density plasma from a metallic lithium foil generated by laser ablation is efficiently injected and accelerated by a radio-frequency quadrupole linear accelerator (RFQ linac). We have obtained a peak beam current of 35 mA accelerated to 1.43 MeV, which is two orders of magnitude higher than a conventional injector and accelerator system can deliver.

Features of mandibular cortical bone morphology in osteoporotic fracture patients.

PURPOSE: The diagnostic criteria for osteoporosis are based on the bone mineral density (BMD) level in the lumbar spine and femur bone. Patients with osteoporotic fractures were diagnosed with osteoporosis. While systemic BMD and mandibular cortical bone morphology are correlated, this has not been studied in patients with a history of osteoporotic fractures. Therefore, purpose of this study was researching the mandibular cortical bone morphology in patients with osteoporotic fractures. METHODS: The subjects were 55 female and 20 male patients with osteoporotic fractures. Patients were divided into 30 primary osteoporosis patients and 45 secondary osteoporosis patients according to the medical history. Patients underwent BMD and panoramic radiography examinations during orthopedic treatment for fractures. A dual-energy X-ray absorptiometry system was used to measure BMD. Mandibular cortex index (MCI) and mandibular cortex width (MCW) were evaluated using machine-learning measurement software. RESULTS: In the analysis of MCI, the ratio of class 2 and 3 was 73% of both primary osteoporosis and secondary osteoporosis. The average MCW was 2.19 mm for primary osteoporosis and 2.30 mm for secondary osteoporosis. The sensitivity values by MCI and MCW were 73% and 76% for both primary and secondary osteoporosis, which were similar detection powers. In addition, the false-negative rates by MCI and MCW were 27% and 24%. CONCLUSION: We suggested that MCI and MCW are indicators of osteoporotic conditions in patients with primary and secondary osteoporosis. Our results show that MCI and MCW are non-inferior to the sensitivity values for lumbar BMD in patients with osteoporotic fractures.

Increased expression of acyl-CoA oxidase 2 in the kidney with plasma phytanic acid and altered gut microbiota in spontaneously hypertensive rats.

We performed a DNA microarray analysis of the renal medulla and cortex from spontaneously hypertensive rats (SHRs), stroke-prone SHRs (SHRSPs), and Wistar-Kyoto (WKY) rats to identify pivotal molecules in the kidney associated with the onset of hypertension and found increased expression of acyl-CoA oxidase 2 (Acox2) mRNA. Real-time polymerase chain reaction revealed that Acox2 mRNA expression in the renal medulla and cortex of SHRs and SHRSPs was increased in comparison to WKY rats. These findings indicate that increased renal ACOX2 (an enzyme that induces the ß-oxidation of fatty acids) is associated with the onset of hypertension. Immunostaining of ACOX2 in the distal tubules from SHRs was stronger than that in the distal tubules from WKY rats. Western blot analysis showed increased expression of ACOX2 protein in renal medulla from SHRs. Regarding the overexpression of ACOX2, plasma levels of phytanic acid in SHRs were significantly higher than those in WKY rats. There were no differences in other short-chain fatty acids. Plasma phytanic acid was affected by the gut microbiota through the conversion from phytol by yeast in the intestinal tract. We compared the gut microbiota profile in three strains of 5-week-old rats by the terminal-restriction fragment length polymorphism method. The gut microbiota profile and ratio of Firmicutes/Bacteroides differed between SHRs and WKY rats. These findings suggest that the increased expression of ACOX2 in the kidney along with increases in plasma phytanic acid and the altered gut microbiota may be involved in the oxidation in the kidney and the pathogenesis of hypertension.

Plasma instability inside solenoid with laser ion source.

Using a solenoid with a laser ion source can suppress divergence of the expanding plasma; however, it has been found that the plasma becomes unstable in a certain magnetic field region. In the previous research, instability of the plasma after the solenoid was found. In this study, we investigated how the plasma instability changes inside the solenoid. A Faraday cup was placed in the solenoid, and the unstable magnetic field range was investigated. This experiment was conducted while changing the Faraday cup position from the inlet to the outlet of the solenoid. By increasing the magnetic field strength, the Faraday cup position indicating a condition triggering instability moved toward upstream in the solenoid. In addition, the instability is gradually mitigated by transporting the laser ablation plasma through the rest of the solenoid. The detailed good working range of the solenoid for the Au1+ beam was also shown.

Prevalence of Zinc Deficiency in Japanese Patients on Peritoneal Dialysis: Comparative Study in Patients on Hemodialysis.

BACKGROUND: It is known that patients on hemodialysis (HD) are prone to developing zinc deficiency due to removal of zinc by HD, inadequate dietary intake, and reduced gastrointestinal zinc absorption. However, the prevalence of zinc deficiency in patients on peritoneal dialysis (PD) has not been well established. METHODS: Serum zinc levels were compared between 47 patients on PD and 47 patients on HD matched for age, sex, and duration of dialysis. A serum zinc level < 60 µg/dL was defined as clinical zinc deficiency and a level of 60-80 µg/dL as subclinical zinc deficiency. The prevalence of zinc deficiency and associated clinical factors were determined in both groups. RESULTS: Clinical zinc deficiency was found in 59.6% of the PD group and 70.2% of the HD group (p = 0.391). Subclinical zinc deficiency was found in 40.4% of the PD group and 29.8% of the HD group. Age, body mass index, and serum albumin level were identified as independent predictors of zinc deficiency in the PD group by multivariate analysis. CONCLUSIONS: A higher prevalence of clinical and subclinical zinc deficiency was found in patients on PD. The rates were comparable between patients on PD and those on HD after adjustment for confounding factors.

Neutron generator based on intense lithium beam driver.

We are proposing a compact neutron generator based on a Li beam driver. The proposed neutron generator comprises a laser ion source, a radio-frequency quadrupole linear accelerator (RFQ linac), a drift tube linac, and a target containing protons. In the generator, the lithium ion is used as a projectile instead of protons to utilize the kinematic focusing technique. The technique enables us to enhance the neutron flux without increasing the beam energy, which is important to develop a clean compact neutron generator. Moreover, the combination of a laser ion source and a RFQ linac with the direct plasma injection scheme will provide several tens of mA of a fully ionized lithium beam, which is much higher than that of conventional heavy ion sources comparable with proton drivers. Neutrons are generated by the nuclear reaction of the lithium ions and protons in the beam target. In this paper, we reported the current status of the development. For RFQ, we designed the RFQ rods to accelerate 40 mA of 7Li3+. We fabricated and installed the rods into a cavity, and, as a first test, accelerated 10 mA of C6+ successfully.

Evaluation of magnetic field error in ExtendedEBIS.

The upgrade of the EBIS, called ExtendedEBIS, is now in progress in Brookhaven National Laboratory. Two 5T-superconducting solenoids have been placed in series with 200 mm distance from each other for higher trap capacity and production of polarized 3He ions. Since the two superconducting solenoids are used, the field error is expected to be larger. In this research, the field error is estimated based on simulation. It was found that the magnetic field line can be 17 mm off from the center axis at the entrance of the collector, and this offset can be adjusted by three types of correction coils. Additionally, mismatch of the spin direction of polarized 3He due to the misalignment was estimated to be small.

Laser power density dependence on charge state distribution of Ta ion laser plasma.

Laser power density per pulse, which is commonly expressed with the unit of "W/cm2," is an important parameter to characterize ablation plasma. To match a design charge state of heavy ion beam induced by a laser ion source, a laser power density must be carefully chosen. Above around 108 W/cm2 of laser power density, laser ablation plasma is emitted from the surface of solid material. Then, up to 109 W/cm2, the most abundant charge state is 1+. Because the ionization energy increases with higher charge states, increasing the laser intensity leads to the charge state distribution shifting higher. Increasing the density to increase charge states also results in lower time of flight due to higher velocities. The maximum laser power density is obtained by the smallest available laser spot size on the target material which is determined by the quality of the laser beam. For many accelerator applications, higher charge state beams are preferred. In particular cases, singly charge ion beams are demanded. Therefore, production of intermediate charge state beams has not been investigated well. In this study, we selected Ta4+ as an example demanded beam and tried to clarify how the transition of charge state distribution depends on laser power density. Conclusively, the possible specification of a laser ion source for Ta4+ delivery was elucidated.

Low charge state lithium beam production from chemical compounds with laser ion source.

In recent years, the primary ion source for the Brookhaven National Laboratory has been the laser ion source, which provides many types of ions within a short switching time of several seconds. The task is difficult for other ion sources. In the previous work, we tested metallic lithium as a target material of the laser irradiation. Although an intense lithium beam was demonstrated, some operational difficulties were observed due to its reactiveness to oxygen. For accelerator applications, a more robust and reliable target material has been demanded. For this purpose, we tested lithium niobate, LiNbO3. Our study investigated the optimization of power density to produce low charge state lithium ions. We struck LiNbO3 with the laser and found lithium ion quantities for five different power densities. Based on the data obtained, we can conclude that the most efficient production of Li1+ occurs when the laser power density is 5 × 108 W/cm2.

Identification of Clock Genes Related to Hypertension in Kidney From Spontaneously Hypertensive Rats.

BACKGROUND: There is a diurnal variation in the blood pressure fluctuation of hypertension, and blood pressure fluctuation abnormality is considered to be an independent risk factor for organ damage including cardiovascular complications. In the current study, we tried to identify molecules responsible for blood pressure circadian rhythm formation under the control of the kidney biological clock in hypertension. METHODS: DNA microarray analysis was performed in kidneys from 5-week-old spontaneously hypertensive rats (SHRs)/Izm, stroke-prone SHR rats (SHRSP)/Izm, and Wistar Kyoto (WKY)/Izm rats. To detect variation, mouse tubular epithelial cells (TCMK-1) were stimulated with dexamethasone. We performed immunostaining and western blot analysis in the renal medulla of kidney from 5-week-old WKY rats and SHRs. RESULTS: We extracted 1,032 genes with E-box, a binding sequence for BMAL1 and CLOCK using a Gene Set Enrichment Analysis. In a microarray analysis, we identified 12 genes increased as more than 2-fold in the kidneys of SHRs and SHRSP in comparison to WKY rats. In a periodic regression analysis, phosphoribosyl pyrophosphate amidotransferase (Ppat) and fragile X mental retardation, autosomal homolog 1 (Fxr1) showed circadian rhythm. Immunocytochemistry revealed PPAT-positivity in nuclei and cytoplasm in the tubules, and FXR1-positivity in the cytoplasm of TCMK-1. In 5-week-old WKY rat and SHR kidneys, PPAT was localized in the nucleus and cytoplasm of the proximal and distal tubules, and FXR1 was localized to the cytoplasm of the proximal and distal tubules. CONCLUSIONS: PPAT and FXR1 are pivotal molecules in the control of blood pressure circadian rhythm by the kidney in hypertension.

Effect of Sucroferric Oxyhydroxide on Fibroblast Growth Factor 23 Levels in Hemodialysis Patients.

OBJECTIVE: This study investigated the effects of sucroferric oxyhydroxide on fibroblast growth factor (FGF)-23 and dose reduction of erythropoiesis-stimulating agents (ESA) and intravenous saccharated ferric oxide in hemodialysis patients. METHODS: In this prospective, open-label, parallel-group, multicenter trial involving patients receiving lanthanum carbonate hydrate, eligible patients were randomized to a sucroferric oxyhydroxide group or a control group. Hemoglobin, serum phosphate, FGF-23, iron, and ferritin levels, as well as transferrin saturation, doses of intravenous saccharated ferric oxide and ESA administered, and the erythropoietin responsiveness index (ERI) were monitored for 24 weeks. RESULTS: Sixty-eight eligible patients were allocated to receive sucroferric oxyhydroxide (n = 34) or serve as controls (n = 34). Data for 31 patients in the sucroferric oxyhydroxide group and 32 in the control group were analyzed. Serum phosphate was equally well controlled in both groups. In the sucroferric oxyhydroxide group, intact FGF-23 levels decreased significantly from baseline at the end of the study (p = 0.01) and there was a significant difference compared with the control group (p = 0.035). Required doses of ESA and ERI were significantly reduced in the sucroferric oxyhydroxide group decreased significantly. The dose of intravenous saccharated ferric oxide required in the sucroferric oxyhydroxide group was significantly lower than that at baseline (p = 0.006) and in the control group (p = 0.003). CONCLUSIONS: Treatment of hyperphosphatemia with sucroferric oxyhydroxide was effective in patients on hemodialysis, resulting in decreased serum FGF-23 levels and a reduction in the required dose of saccharated ferric oxide.

CT imaging features of antiresorptive agent-related osteonecrosis of the jaw/medication-related osteonecrosis of the jaw.

OBJECTIVES: Antiresorptive agent-related osteonecrosis of the jaw (ARONJ)/medication-related osteonecrosis of the jaw (MRONJ) include both bisphosphonate-related osteonecrosis of jaw (BRONJ) and denosumab-related osteonecrosis of jaw (DRONJ). The purpose of this study is to study radiological characteristics of ARONJ/MRONJ. These imaging features may serve as one useful aid for assessing ARONJ/MRONJ. METHODS: CT scans of 74 Japanese patients, who were clinically diagnosed by inclusion criteria of ARONJ/MRONJ, obtained between April 1, 2011 and September 30, 2016, were evaluated. We investigated the CT imaging features of ARONJ/MRONJ, and clarified radiological differentiation between BRONJ and DRONJ, BRONJ due to oral bisphosphonate administration and due to intravenous bisphosphonate administration, BRONJ with respective kinds of medication, BRONJ with long-term administration and short-term administration, BRONJ with each clinical staging respectively. Fisher's exact test, χ2 test, Student's t-test and analysis of variance were performed in the statistical analyses. RESULTS: Unilateral maxillary sinusitis was detected in all patients with upper ARONJ/MRONJ (100%). DRONJ showed large sequestrum more frequently than BRONJ (3/4, 75 vs 3/35, 8.6%, p < 0.05). DRONJ showed periosteal reaction more frequently than BRONJ (4/10, 40 vs 7/65, 10.1%, p < 0.05). Patients of BRONJ resulting from intravenous bisphosphonate administration showed larger and more frequent buccolingual cortical bone perforations than BRONJ resulting from oral bisphosphonate administration (7/8, 87.5 vs 11/30, 36.7%, p < 0.05). There was no significant correlation between CT findings and respective kinds of medication, long/short-term administration, clinical stages of BRONJ. CONCLUSIONS: ARONJ/MRONJ has characteristic CT image findings which could be useful for its assessment.

Development of a Method for Measuring Phytanic Acid as a Lifestyle-related Disease Biomarker in Rat Serum Using Ultra-fast Liquid Chromatography-Ultraviolet Spectrophotometry Combined with a Modified 2-Nitrophenylhydrazine Derivatization Method.

A simple and rapid ultra-fast liquid chromatography-ultraviolet spectrophotometry (UFLC-UV) method combined with modified 2-nitrophenylhydrazine (2-NPH) derivatization was developed for determining phytanic acid (Phy) in rat serum. Serum Phy and heptadecanoic acid (the internal standard) were derivatized by 2-NPH at ambient temperature for 20 min and extracted in n-hexane. After extracting derivatized Phy (D-Phy) and derivatized IS from the reaction mixture, the extracts were separated with a YMC-Pack C8 column (150 × 3.0 mm i.d., S-3 µm) using an isocratic mobile phase comprised of acetonitrile:H2O (90:10; pH 4.4) at 0.5 mL/min. The detection wavelength was 228 nm. Linearity was observed over 1 - 20 µg/mL (r = 0.9997). The intra- and inter-day reproducibilities of D-Phy measurements were ≤13.0%. To our knowledge, this is the first report of the quantitative and qualitative measurement of serum Phy using 2-NPH derivatization and UFLC-UV. This method can be performed rapidly under mild conditions.

Efficacy and safety of saxagliptin, a dipeptidyl peptidase-4 inhibitor, in hemodialysis patients with diabetic nephropathy: A randomized open-label prospective trial.

AIMS: Saxagliptin is a dipeptidyl peptidase-4 inhibitor that was approved in Japan for the treatment of type 2 diabetes in 2013. We examined its efficacy and safety in Japanese hemodialysis patients with diabetic nephropathy. METHODS: In this prospective, open-label, parallel-group study, Japanese hemodialysis patients were randomized to receive either oral saxagliptin (2.5mg/day) or usual care (control group) for 24weeks. Before randomization, patients received fixed doses of conventional antidiabetic drugs (oral drugs and/or insulin) for 8weeks; these drugs were continued during the study. Endpoints included changes in glycated albumin (GA), hemoglobin A1c (HbA1c), postprandial plasma glucose (PPG), and adverse events. RESULTS: Both groups included 41 patients. Mean GA, HbA1c, and PPG decreased significantly in the saxagliptin group (-3.4%, -0.6% [-7mmol/mol], and -38.3mg/dL, respectively; all P<0.0001) but not in the control group (0%, -0.1% [-1mmol/mol], and -3.7mg/dL, respectively) (P<0.0001, P<0.001, and P<0.0001, respectively). In saxagliptin-treated patients, the reduction in GA was significantly greater when saxagliptin was administered as monotherapy than in combination therapy (-4.2% vs. -3.0%, P=0.012) despite similar baseline values (24.5% vs. 23.3%). Reductions in GA, HbA1c, and PPG were greater in patients whose baseline values exceeded the median (23.8% for GA, 6.6% for HbA1c, and 180mg/dL for PPG). There were no adverse events associated with saxagliptin. CONCLUSIONS: Saxagliptin (2.5mg/day) was effective and well tolerated when used as monotherapy or combined with other antidiabetic drugs in Japanese hemodialysis patients with type 2 diabetes. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000018445.

RF synchronized short pulse laser ion source.

A laser ion source that produces shortly bunched ion beam is proposed. In this ion source, ions are extracted immediately after the generation of laser plasma by an ultra-short pulse laser before its diffusion. The ions can be injected into radio frequency (RF) accelerating bucket of a subsequent accelerator. As a proof-of-principle experiment of the ion source, a RF resonator is prepared and H2 gas was ionized by a short pulse laser in the RF electric field in the resonator. As a result, bunched ions with 1.2 mA peak current and 5 ns pulse length were observed at the exit of RF resonator by a probe.

Iron plasma generation using a Nd:YAG laser pulse of several hundred picoseconds.

We investigated the high intensity plasma generated by using a Nd:YAG laser to apply a laser-produced plasma to the direct plasma injection scheme. The capability of the source to generate high charge state ions strongly depends on the power density of the laser irradiation. Therefore, we focused on using a higher power laser with several hundred picoseconds of pulse width. The iron target was irradiated with the pulsed laser, and the ion current of the laser-produced iron plasma was measured using a Faraday cup and the charge state distribution was investigated using an electrostatic ion analyzer. We found that higher charge state iron ions (up to Fe(21+)) were obtained using a laser pulse of several hundred picoseconds in comparison to those obtained using a laser pulse of several nanoseconds (up to Fe(19+)). We also found that when the laser irradiation area was relatively large, the laser power was absorbed mainly by the contamination on the target surface.

Contribution of material's surface layer on charge state distribution in laser ablation plasma.

To generate laser ablation plasma, a pulse laser is focused onto a solid target making a crater on the surface. However, not all the evaporated material is efficiently converted to hot plasma. Some portion of the evaporated material could be turned to low temperature plasma or just vapor. To investigate the mechanism, we prepared an aluminum target coated by thin carbon layers. Then, we measured the ablation plasma properties with different carbon thicknesses on the aluminum plate. The results showed that C(6+) ions were generated only from the surface layer. The deep layers (over 250 nm from the surface) did not provide high charge state ions. On the other hand, low charge state ions were mainly produced by the deeper layers of the target. Atoms deeper than 1000 nm did not contribute to the ablation plasma formation.

Creation of mixed beam from alloy target and couple of pure targets with laser.

To create mixed species ion beam with laser pulses, we investigated charge state distributions of plasma formed from both Al-Fe alloy targets and pure Al and Fe targets placed close together. With two targets, we observed that the two kinds of atoms were mixed when the interval of two laser pulses was large enough (40 µs). On the other hand, when the interval was 0.0 µs, we observed fewer Fe ions and they did not mix well with the Al ions. The two species were mixed well in the plasma from the alloy target. Furthermore, we observed that specific charge states of Fe ions increased. From the results, it was determined that we can use two pure targets to mix two species whose difference of the drift velocity is large. On the other hand, we must use an alloy target when the drift velocities of the species are close.

Investigation of effect of solenoid magnet on emittances of ion beam from laser ablation plasma.

A magnetic field can increase an ion current of a laser ablation plasma and is expected to control the change of the plasma ion current. However, the magnetic field can also make some fluctuations of the plasma and the effect on the beam emittance and the emission surface is not clear. To investigate the effect of a magnetic field, we extracted the ion beams under three conditions where without magnetic field, with magnetic field, and without magnetic field with higher laser energy to measure the beam distribution in phase space. Then we compared the relations between the plasma ion current density into the extraction gap and the Twiss parameters with each condition. We observed the effect of the magnetic field on the emission surface.

Development of the C(6+) laser ablation ion source for the KEK digital accelerator.

A laser ion source that provides a fully ionized carbon ion beam is under joint development at the High Energy Accelerator Research Organization and Brookhaven National Laboratory. Long-pulse (6 ns) and short-pulse (500 ps) laser systems were tested by using them to irradiate a graphite target. Notable differences between the systems were observed in these experiments. Preliminary experimental results, such as the charge-state spectrum, beam intensity, and stability, are discussed.