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Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
Aims
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
Method
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
Results
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Conclusions
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
In this paper, we present a model characterizing the interaction of a radiative shock (RS) with a solid material, as described in a recent paper (Koenig et al., Phys. Plasmas, 24, 082707 (2017)), the new model is then related to recent experiments performed on the GEKKO XII laser facility. The RS generated in a xenon gas cell propagates towards a solid obstacle that is ablated by radiation coming from the shock front and the radiative precursor, mimicking processes occurring in astrophysical phenomena. The model presented here calculates the dynamics of the obstacle expansion, which depends on several parameters, notably the geometry and the temperature of the shock. All parameters required for the model have been obtained from experiments. Good agreement between experimental data and the model is found when spherical geometry is taken into account. As a consequence, this model is a useful and easy tool to infer parameters from experimental data (such as the shock temperature), and also to design future experiments.
The transport of relativistic electron beam in compressed cylindrical targets was studied from a numerical and experimental point of view. In the experiment, cylindrical targets were imploded using the Gekko XII laser facility of the Institute of Laser Engineering. Then the fast electron beam was created by shooting the LFEX laser beam. The penetration of fast electrons was studied by observing Kα emission from tracer layers in the target.
We perform systematic investigation of a new method for generating high-order harmonics, using ablation as the nonlinear medium. We place emphasis on clarifying the pump laser conditions for optimum harmonic yield. For this purpose, we use the Ti:Sapphire laser beams of the advanced laser light source (800 nm wavelength, 360 mJ total energy). We have independently varied the intensity of the prepulse (which creates the plasma ablation) and the intensity of the main pulse (which generates the harmonics), and studied their influence on the harmonic intensity. We show here that the presence of doubly ionized atoms in the ablation, created either by a strong prepulse intensity or by irradiating the main pulse, will suppress harmonic generation.
This study investigated a new effective method for controlling the capsalid monogenean Neobenedenia girellae. We examined in vitro and in vivo the effect on the percentage survival of N. girellae in buffers containing different metallic ions. Decreased survival was observed in buffer solutions lacking two ions. In particular, the percentage survival of N. girellae was significantly decreased after 10 min exposure to buffer containing neither Ca2+ nor Mg2+. Transmission electron microscopic observations showed that treatment with this buffer disrupted intercellular junctions. This significant effect on percentage survival of N. girellae using Ca2+/Mg2+-free buffer was confirmed in an in vivo assay. Ca2+/Mg2+-free buffer had no effect on the condition of the host, spotted halibut Verasper variegates (Pleuronectidae). These results suggest that treatment with Ca2+/Mg2+-free buffer is a new effective control method, which could replace existing control methods.
We describe here the present status of the Advanced Laser Light Source
(ALLS) facility, a state-of-the-art multi-beam Ti:sapphire laser system
presently under construction in Canada. ALLS is a national user facility
to be commissioned in 2005 at the INRS campus near Montreal. The 25 fs
ALLS multi-beam laser system has three components, each with different
repetition rate and output energy. These multiple laser beams will be used
to generate a “rainbow” of femtosecond pulses from the far
infrared to hard X-rays, which can be combined to perform unique
experiments, such as dynamic molecular imaging. In this paper, we describe
two examples of experiments that are planned by our group with the ALLS
facility. The first is the highly efficient generation of high-order
harmonics using ablation medium. We demonstrate the generation of up to
the 53rd harmonics (λ = 15 nm) of a Ti:sapphire laser pulse
(150 fs, 10 mJ), using pre-pulse (210 ps, 24 mJ) produced boron ablation
as the nonlinear medium. The second example is the demonstration of
in-line phase-contrast imaging with an ultrafast (300 fs) laser-based hard
X-ray source (Mo K-α line). Images of biological samples have shown
great enhancement of contrast due to this technique, distinguishing
details that are barely observable or even undetectable in absorption
images.
The effect of thin Ti/PbZr0.4Ti0.6O3 seed layers on the properties of PbZr0.4Ti0.6O3 (PZT) capacitors has been investigated. The seed layer is based on a bi-layer of thin Ti and thin PZT with a total thickness ranging from 10 to 25 nm, which was deposited on Ir/Pt or Ir/IrO2/Pt by sputtering. After crystallization of the seed layers the main 130-nm-thick PZT film was deposited and crystallized. As a result, a highly preferred (111)-orientation of the PZT was obtained on a 10-nm-thick seed layer, where the peak intensity ratios of (111)/{100} and (111)/{110} are about 100 and 20, respectively. The 10-nm-thick seed forms a pyrochlore phase with a very smooth surface, where the formation of the pyrochlore phase is attributed to Pb diffusion, resulting in a Pb deficient stoichiometry. The seed layer transformed to the perovskite phase during the main PZT crystallization. It is shown that an IrO2 layer beneath the Pt can prevent Pt layer degradation related to the volume expansion due to the oxidation of Ir during the main PZT crystallization. Capacitors with the 10-nm-thick seed layer fabricated on the Ir/Pt and Ir/IrO2/Pt substrates showed typical 2 Pr values of 44.0 μC/cm2 and 41.2 μC/cm2, respectively. The voltage found for 90%-polarization saturation is about 3.0 V, and the capacitors are fatigue-free at least up to 1010 switching cycles.
The generation of coherent soft X rays is studied using a terawatt
picosecond Nd:glass laser system. Two different methods are
investigated as candidates for efficient generation of such
radiation, namely, longitudinally pumped transient collisional
excitation nickel-like molybdenum X-ray laser, and high-harmonic
generation from solid–vacuum interfaces. In the course
of experiments on longitudinally pumped X-ray lasers, unexpected
jetlike structures are observed in the visible emission of the
molybdenum plasma, extending over a length of several millimeters.
An interesting characteristic of this phenomena is that clear jets
are observed only for longitudinal pump intensities between 5 ×
1014 and 7 × 1014 W/cm2. The
effects of a finite scale length density gradient on surface harmonics
is also investigated. The efficiency of harmonic generation from
near-solid density plasma is found to increase by a factor of 2 to 3
when using prepulses. The scale length of the preplasma is simulated
using a one-dimensional hydrodynamic code, and the increase in efficiency
is verified to be in accordance with particle-in-cell simulation results.
For high density FeRAM devices small cell sizes are essential. The combination of the capacitor on plug (COP) structure with the Chain FeRAM™ cell design is used to develop a 32Mb FeRAM. Based on a 0.2 μm standard CMOS process a silicide capped polysilicon plug is used to contact the bottom electrode of the ferroelectric capacitor to the transistor. The barrier contact to the plug is formed by IrO2/Ir and a sputter deposited PZT (40/60) is used as ferroelectric material. The function of SrRuO3 (SRO) layers at the electrode/PZT interfaces is described in more detail. Double sided SRO results in slightly lower coercive voltage and imprint behavior compared to capacitors without SRO. Double sided SRO is essential to achieve excellent fatigue behavior measured up to 1×1011 switching cycles.
Flyer acceleration experiments are carried out using a KrF
laser system with a pulse duration of 10–15 ns and an
intensity of ∼1.0 × 1013 W/cm2.
Three-layered targets (aluminum–polyimide–tantalum)
are used. First, an average velocity of laser-driven tantalum
flyers with a thickness of 4 and 8 μm is estimated. Then,
in a collision of a flyer with a copper layer attached to a
diamond plate, we measure a transit time of a shock wave in
the diamond. The impact velocity is estimated based on the transit
time and a numerical simulation. This numerical simulation also
shows that the initial peak pressure caused by the impact of
a 4-μm-thick flyer is kept at 11 Mbar for 12–13 μm
in thickness. Finally, whether this thickness is enough for
EOS measurements is discussed.
Epidemiological and experimental evidence suggests that maternal undernutrition during pregnancy may alter development of fetal organ systems. We have demonstrated previously that fetal hypothalamic-pituitary-adrenal (HPA) axis responses to exogenous corticotropin-releasing hormone (CRH) + arginine vasopressin (AVP), or adrenocorticotrophin hormone (ACTH), are reduced in fetuses of mildly undernourished ewes. To examine these effects further we tested HPA axis responses to acute isocapnic hypoxaemia in fetal sheep at 114-129 days gestation (dGA), following 15 % reduction in maternal nutritional intake between 0 and 70 dGA. Fetuses from control (C) and nutrient-restricted (R) ewes were chronically catheterised and plasma ACTH and cortisol responses were determined at 114-115, 120-123 and 126-129 dGA during hypoxaemia (1 h) induced by lowering the maternal inspired O2 fraction (FI,O2). Basal plasma cortisol concentrations and HPA axis responses at 114-115 and 120-123 dGA did not differ between C and R fetuses. At 126-129 dGA, both plasma ACTH (P < 0.01) and cortisol (P < 0.05) responses were smaller in R fetuses compared to C fetuses. Fetal blood gas status, fetal body weight, body proportions and organ weights did not differ between the groups. We conclude that mild maternal undernutrition alters development of the fetal HPA axis producing a reduction in pituitary and adrenal responsiveness to endogenous stimuli.
Seyfert galaxies often have extended emission line regions around their nucleus. We started an observation program of optical tridimensional spectroscopy for circumnuclear regions of nearby Seyfert galaxies to investigate the ionization source of the gas of just vicinity(typically several hundred pc) of nucleus.
A narrow-band imaging observation of the Seyfert galaxy NGC1068 was made in the Fabry-Perot mode of the Kyoto 3D Spectrograph attached to the 188cm telescope of the Okayama Astrophysical Observatory. We observed at wavelengths of Hα, [S ii]λ6716, [S ii]λ6731 and adjacent continua of the respective lines with a “tunable filter”, i.e. a gap-scanning etalon with a spectral resolution of 20 Å.
The Kyoto 3-D Spectrograph was commissioned successfully at the 188-cm telescope of the Okayama Astrophysical Observatory in the spring of 1996. This instrument has four distinct modes (Ohtani et al. 1994): (1) narrow-band imager, which is an ordinary focal-reducer camera; (2) Spectro-NebulaGraph (long-slit spectrograph; Kosugi et al. 1995); (3) imaging Fabry-Perot interferometer, using either of two Fabry-Perot etalons from Queensgate Instruments (a tunable filter with R = 300 and another with R = 7000 for velocity-field observations. Broad-band (400–700 nm) coatings are deposited on both etalons. During observations, the etalon temperature is stabilized within 0.5°C); and (4) integral-field spectrograph of the TIGER-type (Bacon et al. 1995). In this mode, the spectra of 7 × 11 objects can be recorded simultaneously, along with 7 × 2 spectra of the sky 4′ away. The spatial resolution is 1″.3 and the field of view is 9″ × 14″.
Some nonlinear electrical characteristics in electroluminescent porous silicon (PS) diodes with a relatively thin PS layer (0.5–5 μm thick) are described. The experimental PS diodes were composed of a semitransparent Au film, a PS layer, p- or n-type Si substrate, and an ohmic back contact. The PS layers were prepared by anodizing Si wafers in an ethanoic HF solution. In some cases, the PS layers were treated by rapid thermal oxidization (RTO) process. When the bias voltage is applied, the PS diodes show the electrical behavior like the metal-insulator-semiconductor (MIS) diodes. The negative-resistance characteristics and memory effect are also observed. These results indicate that the quantum-structured nature of the PS layer appears not only in the optical properties but also in the electrical properties.
A microcylinder target is proposed for a recombination X-ray laser generation and is investigated by a numerical simulation. The size of the target is of the order of 1 cm in the axial direction and 100 μm in the inner radius. The target has an axial slit of 20 μm wide through which a line-focused laser illuminates the inner wall. The hot plasma produced inside is confined, and a part of this is blown out through the slit. This plasma cools due to the free expansion, so that a gain of a recombination X-ray laser appears outside the microcylinder. When a large enough amount of hot plasma is produced inside, it plays the role of a reserver. Numerical results show that the quasi-cw (continuous wave) gain of Hα line is obtained outside the aluminum microcylinder when the plasma, which has not recombined yet, is supplied continuously.
Some optoelectronic effects in porous Si (PS) have been investigated in relation to the visible luminescence mechanism. As regards photoluminescence (PL), particular emphasis is placed on the relationship between photoconduction (PC) and PL excitation (PLE) spectra, the interaction of external electric field and PL emission, and polarization properties of PL Main subjects of electroluminescence (EL) studies reported here are the dynamic behavior of EL operation and the formation of a large-area contact by a conducting polymer (polypyrrole: PP). The observed experimental results (almost complete coincidence of PC spectra with PLE ones, linear polarization memory of PL definite correlation between the polarization degree and the PL efficiency, and comparable response time of electrical PL quenching and EL to the PL decay time) are consistent with our hypothesis that the major process of PL takes place within Si nanocrystallites. The electrical characterization of light-emitting PS diodes with PP contacts ensures the usefulness of the contact formation by electropolymerization as a technique for uniform and efficient carrier injection into PS.
This paper presents a new method to generate a smooth collision-free path of a mobile robot. The path is generated as follows: First, the obstacle spaces are artificially contracted to obtain an initial collision-free path which leads the mobile robot from the start point to the goal; then the path is iteratively modified to avoid the obstacle spaces which are gradually restored (this is carried out in consideration of the index introduced to evaluate the correctness of the path), in the final step, all the obstacle spaces are fully restored and the obtained path becomes a desirable collision-free one. The proposed method is effectively applied to an example of planning planar movements of a mobile robot.
Manipulator joint trajectories are planned to make an arbitrary cost function as good as possible in consideration of physical constraints based on kinematics and dynamics of a manipulator system. An algorithm presented in this paper is an iteratively improving method using the local controllability of B spline. It can be also applied to the case that some points are specified and joint trajectories must pass through those points. This algorithm is applied to an example of trajectory planning of a manipulator with two links and two degrees of freedom.