A compact and stable incidence-plane-rotating second harmonics detector.

We describe a compact and stable setup for detecting the optical second harmonics, in which the incident plane rotates with respect to the sample. The setup is composed of rotating Fresnel rhomb optics and a femtosecond ytterbium-doped fiber laser source operating at the repetition frequency of 10 MHz. The setup including the laser source occupies an area of 1 m2 and is stable so that the intensity fluctuation of the laser harmonics can be less than 0.2% for 4 h. We present the isotropic harmonic signal of a gold mirror of 0.5 pW and demonstrate the integrity and sensitivity of the setup. We also show the polarization-dependent six-fold pattern of the harmonics of a few-layer WSe2, from which we infer the degree of local-field effects. Finally, we describe the extensibility of the setup to investigate the samples in various conditions such as cryogenic, strained, ultrafast non-equilibrium, and high magnetic fields.

High repetition pump-and-probe photoemission spectroscopy based on a compact fiber laser system.

The paper describes a time-resolved photoemission (TRPES) apparatus equipped with a Yb-doped fiber laser system delivering 1.2-eV pump and 5.9-eV probe pulses at the repetition rate of 95 MHz. Time and energy resolutions are 11.3 meV and ∼310 fs, respectively, the latter is estimated by performing TRPES on a highly oriented pyrolytic graphite (HOPG). The high repetition rate is suited for achieving high signal-to-noise ratio in TRPES spectra, thereby facilitating investigations of ultrafast electronic dynamics in the low pump fluence (p) region. TRPES of polycrystalline bismuth (Bi) at p as low as 30 nJ/mm2 is demonstrated. The laser source is compact and is docked to an existing TRPES apparatus based on a 250-kHz Ti:sapphire laser system. The 95-MHz system is less prone to space-charge broadening effects compared to the 250-kHz system, which we explicitly show in a systematic probe-power dependency of the Fermi cutoff of polycrystalline gold. We also describe that the TRPES response of an oriented Bi(111)/HOPG sample is useful for fine-tuning the spatial overlap of the pump and probe beams even when p is as low as 30 nJ/mm2.

Emergent photovoltage on SmB6 surface upon bulk-gap evolution revealed by pump-and-probe photoemission spectroscopy.

Recent studies suggest that an exemplary Kondo insulator SmB6 belongs to a new class of topological insulators (TIs), in which non-trivial spin-polarized metallic states emerge on surface upon the formation of Kondo hybridization gap in the bulk. Remarkably, the bulk resistivity reaches more than 20 Ω cm at 4 K, making SmB6 a candidate for a so-called bulk-insulating TI. We here investigate optical-pulse responses of SmB6 by pump-and-probe photoemission spectroscopy. Surface photovoltage effect is observed below ~90 K. This indicates that an optically-active band bending region develops beneath the novel metallic surface upon the bulk-gap evolution. The photovoltaic effect persists for >200 µs, which is long enough to be detected by electronics devices, and could be utilized for optical gating of the novel metallic surface.

Direct evidence for three-dimensional off-axis trapping with single Laguerre-Gaussian beam.

Optical tweezers are often applied to control the dynamics of objects by scanning light. However, there is a limitation that objects fail to track the scan when the drag exceeds the trapping force. In contrast, Laguerre-Gaussian (LG) beams can directly control the torque on objects and provide a typical model for nonequilibrium systems such as Brownian motion under external fields. Although stable "mid-water" trapping is essential for removing extrinsic hydrodynamic effects in such studies, three-dimensional trapping by LG beams has not yet been clearly established. Here we report the three-dimensional off-axis trapping of dielectric spheres using high-quality LG beams generated by a special holographic method. The trapping position was estimated as ~ half the wavelength behind the beam waist. These results establish the scientific groundwork of LG trapping and the technical basis of calibrating optical torque to provide powerful tools for studying energy-conversion mechanisms and the nonequilibrium nature of biological molecules under torque.

Time-resolved photoemission apparatus achieving sub-20-meV energy resolution and high stability.

The paper describes a time- and angle-resolved photoemission apparatus consisting of a hemispherical analyzer and a pulsed laser source. We demonstrate 1.48-eV pump and 5.92-eV probe measurements at the ⩾10.5-meV and ⩾240-fs resolutions by use of fairly monochromatic 170-fs pulses delivered from a regeneratively amplified Ti:sapphire laser system operating typically at 250 kHz. The apparatus is capable to resolve the optically filled superconducting peak in the unoccupied states of a cuprate superconductor, Bi2Sr2CaCu2O(8 + δ). A dataset recorded on Bi(111) surface is also presented. Technical descriptions include the followings: A simple procedure to fine-tune the spatio-temporal overlap of the pump-and-probe beams and their diameters; achieving a long-term stability of the system that enables a normalization-free dataset acquisition; changing the repetition rate by utilizing acoustic optical modulator and frequency-division circuit.

[Causal inference in medicine--decision making].

In the field of occupational medicine, either when we consider some preventive plans or when we make decisions to compensate for occupational diseases, it has been necessary to discuss causality between work and disease. Furthermore, epidemiologic causality has recently been used in risk assessment in occupational and environmental settings. We have shown that the law of causality in medicine is recognized as probability and continuous variables. Such a law of causality has been recognized in the same way as probability in physics, too, and has been regarded as a model of science. Physicists and mathematicians had claimed the importance of probability in causal inference as well as the principle of uncertainty before it was discovered. We, then, explained Etiologic Fraction (EF), Attributable Proportion for the Exposed Population (APE), Probability of Causation (PC), and so on. The PC has been used to ascertain the conditional probability in an individual case of a disease having been caused by a particular prior exposure, by using the experience of exposed populations to determine the appropriate relative risk, and this has been used for compensation for exposed cases. Next the applicability of information from a population to individuals was presented. Third, we provided a brief historical aspect of epidemiology. The evolutions in Epidemiology have been very rapid, so we pointed out that, in Japan, we could observe many incommensurable phenomena in epidemiologists and physicians depending on the era which was studied by them. Fourth, we discussed judgement and political application based on epidemiologic evidence, using Yanagimoto's classification is also taken or not should be estimated and compared. We presented several examples of reasoning in judgements. Lastly, we discussed several tasks and assignments for the future of epidemiology.

Smoking and mental health: cross-sectional and cohort studies in an occupational setting in Japan.

BACKGROUND: The relationship between smoking and mental health remains unclear. METHODS: We carried out a cross-sectional study and a cohort study on the possible association of smoking and mental health in 782 workers. Using a questionnaire including the 30-item General Health Questionnaire (GHQ-30) and items related to the smoking state, the association between smoking and mental health was evaluated separately in males and females. The subjects were classified into smokers and nonsmokers, and changes in the GHQ score during a 2-year follow-up period were evaluated. To control potential confounding factors, multiple regression analyses were performed. RESULTS: The cross-sectional study showed no difference in the GHQ score between smokers and nonsmokers among males but a significantly higher GHQ score for smokers than nonsmokers among females. This difference among females was confirmed to be significant by multiple regression analysis. The 2-year cohort study showed a decrease in the GHQ score in each group and no reduction in the difference in the GHQ score between smokers and nonsmokers among females. CONCLUSIONS: No difference was observed in mental health between smokers and nonsmokers in males. However, in females, smokers showed poorer mental health than nonsmokers, and this difference remained unchanged even after 2 years.

A case-control study of the relationships among silica exposure, gastric cancer, and esophageal cancer.

BACKGROUND: We examined the effect of silica exposure on gastric and esophageal cancer mortality using a cancer control series in a population setting. METHODS: Cases and controls were restricted to male subjects and were drawn from death certificates in the Tobi area of Japan. A control group was selected from a series of deaths due to colon cancer, and cancers of other organs. The Japanese death certificate system is comprehensive because all deaths must be reported to the local office and death certificates are written by medical doctors. Age and smoking habits adjusted the Mantel-Haenszel odds ratios were estimated. RESULTS: For gastric cancer, the age-, smoking-adjusted odds ratios were 1.22 (95% CI 0.74-2.01) for colon cancer and the other cancer control for silica exposure work, and 1. 36 (95% CI 0.76-2.43) for silicosis. For esophageal cancer, the age- and smoking-adjusted odds ratios were 1.53 (95% CI 0.59-3.96) for the cancer control for silica exposure, and 2.33 (95% CI 0.87-6.23) for silicosis, respectively. CONCLUSIONS: The results suggest that gastric and esophageal cancer were related to silica exposure and silicosis in the study area, although they did not reach a statistically significant level because of the small sample size. The estimated odds ratios were higher for esophageal cancer and silicotic patients.

Does smoking cessation improve mental health?

There is a possibility that cessation of smoking improves mental health, but there are no studies that have demonstrated this. A cohort study was performed for 1 year in 18 males who spontaneously stopped smoking (cessation group) and 173 who continued to smoke (smoking group). The mental health state was evaluated using the Japanese version of the 30-item General Health Questionnaire (GHQ-30) before the cessation of smoking and 6 months and 1 year after smoking cessation. Changes in the GHQ score were compared between the cessation and smoking groups. In order to control the effects of confounding factors, multiple regression analyses were performed using the GHQ score after 6 months and 1 year as dependent variables. The GHQ score in the cessation group significantly decreased 6 months and 1 year after smoking cessation (P < 0.04 and 0.01, respectively, by paired t-test). In the smoking group, the GHQ score slightly decreased. Repeated measure analysis of variance revealed that the decrease in the GHQ score in the cessation group was significantly larger than in the smoking group. Multiple regression analysis revealed significant effects of smoking cessation on mental health after controlling for other confounding factors. It can be concluded that smoking cessation may improve mental health.

Evaluation of gravity-dependent membrane potential shift in Paramecium.

It is still debated whether or not gravity can stimulate unicellular organisms. This question may be settled by revealing changes in the membrane potential in a manner depending on the gravitational forces imposed on the cell. We estimated the gravity-dependent membrane potential shift to be about 1 mV G-1 for Paramecium showing gravikinesis at 1-5 G, on the basis of measurements of gravity-induced changes in active propulsion and those of propulsive velocity in solutions, in which the membrane potential has been measured electrophysiologically. The shift in membrane potential to this extent may occur from mechanoreceptive changes in K+ or Ca2+ conductance by about 1% and might be at the limit of electrophysiological measurement using membrane potential-sensitive dyes. Our measurements of propulsive velocity vs membrane potential also suggested that the reported propulsive force of Paramecium measured in a solution of graded densities with the aid of a video centrifuge microscope at 350 G was 11 times as large as that for -29 mV, i.e., the resting membrane potential at [K+]o = 1 mM and [Ca2+]o = 1 mM, and, by extrapolation, that Paramecium was hyperpolarized to -60 mV by gravity stimulation of 100-G equivalent, the value corrected by considering the reduction of density difference between the interior and exterior of the cell in the graded density solution. The estimated shift of the membrane potential from -29 mV to -60 mV by 100-G equivalent stimulation, i.e., 0.3 mV G -1, could reach the magnitude entirely feasible to be measured more directly.

Muscle relaxant action of MS-322, a new centrally acting muscle relaxant, in rats.

1. The pharmacological properties of (R)-(+)-3-phenyl-5-¿2-(1-pyrrolidinylmethyl)-butyryl¿isoxazole hydrochloride (MS-322) were investigated and compared with those of other muscle relaxants. 2. MS-322 (3-12 mg/kg, IV) reduced spinal reflex potentials in acutely spinalized rats dose dependently. Its inhibitory effects on polysynaptic and dorsal root reflexes were more marked than those on the monosynaptic reflex. 3. MS-322 (1.5-12.0 mg/kg, IV) depressed the afferent discharges of de-efferented muscle spindles in anesthetized rats dose dependently. 4. The inhibitory effect of MS-322 on this afferent activity was considered to be due to its membrane stabilizing action. 5. In addition to the central effects of MS-322, its effect on muscle spindles may contribute to its muscle relaxant activity.

Pharmacological properties of the new centrally acting muscle relaxant (R)-(+)-3-phenyl-5-[2-(1-pyrrolidinylmethyl)butyryl]isoxazole hydrochloride.

The pharmacological properties of (R)-(+)-3-phenyl-5-[2-(1-pyrrolidinylmethyl)butyryl]isoxazole hydrochloride (CAS 144576-50-1, MS-322), a new centrally acting muscle relaxant, were investigated and compared with those of eperisone-HCl (CAS 56839-43-1) in experimental animals. MS-322 (1.5-6 mg/kg i.v.) reduced both anemic and intercollicular decerebration-induced rigidity in rats. Similar doses were required for these effects. The activity of MS-322 (200 mg/kg p.o.) against intercollicular decerebration-induced rigidity was greater and longer lasting than that of the same dose of eperisone-HCl. MS-322 (0.75-6 mg/ kg i.v.) inhibited the flexor reflex in anesthetized cats in a dose-dependent manner and more strongly than eperisone-HCl. MS-322 had no effect on the neuromuscular junction in anesthetized rats. The muscle relaxant activity of MS-322 in mice, demonstrated by the traction and rota-rod tests was stronger than that of eperisone-HCl, whereas MS-322 affected spontaneous motor activity in mice less than eperisone-HCl. The results of this study suggest that MS-322 is a potent centrally acting muscle relaxant with relatively weak depressant activity at other central nervous system pathways.

Characterization of alpha 1-adrenoceptor subtypes in rat spinal cord.

The alpha 1-adrenoceptor subtypes in ventral and dorsal horns of rat lumbar spinal cord were studied. High concentrations of the alpha 1D-adrenoceptor antagonist, BMY 7378 (8-[2-[4-(2-methoxyphenyl) 1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride), displaced bound [3H]prazosin in a single-site manner and the binding affinity was close to those for alpha 1A- and alpha 1B-adrenoceptor binding sites. 5-Methyl-urapidil displaced bound [3H]prazosin in a two site manner and the high and low affinities were close to those of alpha 1A- and alpha 1B-adrenoceptor binding sites, respectively. The alpha 1-adrenoceptor subtype populations of ventral and dorsal horns did not differ. The alpha 1A- and alpha 1B-adrenoceptor populations comprised 70% and 30%, respectively, of the total and very few alpha 1D-adrenoceptors were detected.

Immunocytochemical localization of bone morphogenetic proteins (BMPs) in salivary gland pleomorphic adenoma.

The localization of bone morphogenetic protein (BMP)-1, -2, -3 and transforming growth factor (TGF)-beta in normal salivary gland and pleomorphic adenoma of the salivary gland has been examined immunocytochemically. Tumor cells with BMP immunostaining in pleomorphic adenoma were associated with some solid cellular and tubuloglandular patterns, and with stellate cells in the myxoid area. In addition, in the chondroid area of three pleomorphic adenomas, chondrocyte-like cells were positive for BMPs. It is speculated that BMPs secreted by the tumor cells play a role in the formation of the chondroid component in pleomorphic adenoma by inducing some tumor cells, probably neoplastic myoepithelial cells, to differentiate to chondrocytes by metaplastic change. No tumor cells specifically immunostained with TGF-beta were found. TGF-beta was positive in fibrous and hyalinized stroma. In the submandibular gland, only anti-BMP-1 antibody specifically reacted to apical portions of degenerated serous acinar cells.

[Accumulation of a disopyramide metabolite in renal failure].

Twenty-nine cases of hypoglycemia induced by disopyramide (DP) have been reported in the literature to date. Twenty of the reported cases showed hypo-renal function and a high concentration was rare. DP is metabolized to mono-N-dealkyldisopyramide (MND) in the liver and accumulation of MND is to be expected in renal failure. Both DP and MND bind mainly to alpha-1-acid glycoprotein (AAG) in the plasma. In 10 hemodialysis (HD) patients with normal liver function receiving DP therapy in the steady state. DP, MND and AAG were measured pre- and post-HD. Ten patients with normal renal and liver function were selected as the controls. The DP concentration was 2.08 +/- 0.39 micrograms/ml (mean +/- SD) in the control group, and the pre- and post-HD levels were 2.40 +/- 1.08 micrograms/ml and 1.73 +/- 0.87 micrograms/ml, respectively, in the HD group. The MND concentration was 0.42 +/- 0.23 micrograms/ml in the controls, 1.53 +/- 0.52 micrograms/ml in pre-HD and 1.08 +/- 0.32 micrograms/ml in post-HD. Although DP and MND are both classified as substances of small molecular weight, the average decrease in plasma concentration from pre- to post-HD was under 30% with both agents. The MND/DP ratio in the HD group was higher than in the controls, but there was no significant difference between pre- and post-HD. The AAG level was 75 +/- 5mg/dl in the controls and 109 +/- 11mg/dl before HD in the HD group (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Venovenous compares favorably with venoarterial access for extracorporeal membrane oxygenation in neonatal respiratory failure.

Traditional extracorporeal membrane oxygenation via the venoarterial route requires cannulation and ligation of the internal jugular vein and common carotid artery. Concerns about ligation of the common carotid artery prompted development of a 14F double-lumen internal jugular vein cannula for venovenous oxygenation for neonates with respiratory failure. We retrospectively compared 22 patients supported by venovenous bypass and 20 patients supported with traditional venoarterial bypass. The two groups of patients were selected to be comparable in terms of diagnosis and severity of respiratory insufficiency. The diagnoses in both groups were limited to meconium aspiration syndrome or persistent pulmonary hypertension of the newborn. The average oxygenation indexes in the two groups were similar (46.6 venovenous, 47.2 venoarterial, p = not significant). Venovenous access allowed flow rates of more than 100 ml/kg per minute, which were adequate for gas exchange support. One patient required conversion from venovenous to venoarterial bypass because of hemodynamic instability. The average time of bypass support was 115 hours (range 24 to 338 hours) for venovenous bypass and 134 hours (range 47 to 361 hours) for venoarterial bypass (p < 0.05). The time to extubation after decannulation from extracorporeal membrane oxygenation was 133 hours (range 38 to 720 hours) for venovenous support and 100 hours (range 27 to 192 hours) for venoarterial support (p = not significant). One patient supported with venoarterial bypass had an intracranial hemorrhage. There were no documented neurologic injuries in the patients managed with venovenous bypass. There were no deaths in either group. Venovenous extracorporeal membrane oxygenation through a double-lumen cannula can adequately provide respiratory support for neonates with pulmonary failure and effectively avoids ligation of the common carotid artery.

Accumulation of a disopyramide metabolite in renal failure.

Ten hemodialysis (HD) patients with normal liver function received disopyramide (DP) therapy in the steady state. DP, mono-N-dealkyldisopyramide (MND) and alpha-1-acid glycoprotein (AAG) were measured before and after HD. Ten patients with normal renal and liver function were selected as controls. The DP concentration was 2.08 +/- 0.39 micrograms/ml (mean +/- SD) in the control group, and the pre and post HD levels were 2.40 +/- 1.08 micrograms/ml and 1.73 +/- 0.87 micrograms/ml, respectively, in the HD group. The MND concentration was 0.42 +/- 0.23 microgram/ml in controls, 1.53 +/- 0.52 micrograms/ml in pre HD and 1.08 +/- 0.32 microgram/ml in post-HD. Although DP and MND are both classified as small molecular weight substances, the average decrease in plasma concentration from pre to post HD was under 30% with both agents. The MND/DP ratio in the HD group was higher than in controls, but there was no significant difference between pre and post HD. The AAG level was 75 +/- 5 mg/dl in controls and 109 +/- 11 mg/dL before HD in the HD group (p < 0.001). In conclusion, an MND accumulation was observed in HD patients receiving DP therapy. Because the anticholinergic effect of MND is 24 times that of DP, MND is thought to contribute in some way to the hypoglycemia induced by DP in renal failure.