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Lurasidone has demonstrated efficacy in the treatment of schizophrenia in a series of short-term placebo-controlled trials.
To evaluate the safety, tolerability and effectiveness of lurasidone in the long-term treatment of patients with a DSM-IV-TR diagnosis of schizophrenia.
Patients who completed a 6 week, double-blind, placebo-controlled trial received once-daily, flexible-doses of lurasidone, 40–120 mg in a 22 month open-label extension study. An observed case analysis was performed on change from pre-treatment baseline in safety and efficacy parameters.
250 subjects entered the study; 39.8% completed 12 months and 26.8% completed 22 months of treatment. Lurasidone treatment was associated with a mean endpoint change in weight of +0.7 kg. Median endpoint change at Month 12 and Month 24, respectively, was -1.0 and −9.0 mg/dL for total cholesterol; 0.0 and −1.0 mg/dL for LDL; +1.0 and −11.0 mg/dL for triglycerides; +4.0 and +2.0 mg/dL for glucose; 0.0 and +0.1% for HbA1c; and −1.3 and −1.1 ng/mL for prolactin. The mean PANSS total score was 69.5 at extension baseline. The mean (95% CI) endpoint change from extension baseline in PANSS total score was −0.5 (95%-CI: −0.7, −0.3). Overall, 14.7% of patients discontinued due to an adverse event. Adverse events occurring with an incidence ≥10% were schizophrenia (12.4%), akathisia (10.8%) and somnolence (10.8%).
In this 22 month extension study, treatment with lurasidone was associated with minimal effects on weight, glucose, and lipids. Subjects demonstrated sustained improvement in the PANSS total score for up to 24 months of lurasidone treatment.
While echocardiographic parameters are used to quantify ventricular function in infants with single ventricle physiology, there are few data comparing these to invasive measurements. This study correlates echocardiographic measures of diastolic function with ventricular end-diastolic pressure in infants with single ventricle physiology prior to superior cavopulmonary anastomosis.
Data from 173 patients enrolled in the Pediatric Heart Network Infant Single Ventricle enalapril trial were analysed. Those with mixed ventricular types (n = 17) and one outlier (end-diastolic pressure = 32 mmHg) were excluded from the analysis, leaving a total sample size of 155 patients. Echocardiographic measurements were correlated to end-diastolic pressure using Spearman’s test.
Median age at echocardiogram was 4.6 (range 2.5–7.4) months. Median ventricular end-diastolic pressure was 7 (range 3–19) mmHg. Median time difference between the echocardiogram and catheterisation was 0 days (range −35 to 59 days). Examining the entire cohort of 155 patients, no echocardiographic diastolic function variable correlated with ventricular end-diastolic pressure. When the analysis was limited to the 86 patients who had similar sedation for both studies, the systolic:diastolic duration ratio had a significant but weak negative correlation with end-diastolic pressure (r = −0.3, p = 0.004). The remaining echocardiographic variables did not correlate with ventricular end-diastolic pressure.
In this cohort of infants with single ventricle physiology prior to superior cavopulmonary anastomosis, most conventional echocardiographic measures of diastolic function did not correlate with ventricular end-diastolic pressure at cardiac catheterisation. These limitations should be factored into the interpretation of quantitative echo data in this patient population.
The effects of backward inclination angle on flow characteristics and jet dispersion properties of a stack-issued jet in crossflow were studied by means of instantaneous and long-exposure photography, particle image velocimetry (PIV), and tracer-gas concentration detections at a Reynolds number of 2,400, a jet-to-crossflow momentum flux ratio of 1.0, and the backward inclination angles θ = 0° - 60°. Three characteristic flow patterns featured by different near-wake flow structures were found within the surveyed span of the backward inclination angle: low (θ ≤ 25°), mediate (25° < θ < 50°), and high (θ ≥ 50°). In the range of low backward inclination angle, mushroom vortices appeared in the upwind shear layer. Jet fluids were entrained into the jet- and tube-wakes because the near wake region was characterized by a jet-wake vortex and a downwash flow. In the range of mediate backward inclination angle, forward-rolling vortices were formed in the upwind shear layer. Jet fluids were entrained into the jet wake but not appearing in the tube wake because the near wake was characterized by an isolated tube wake and up-going flows. In the range of high backward inclination angle, small-sized forward-rolling vortices were observed in the upwind shear layer. Jet fluids were not observed in both the jet- and tube-wakes because all flows went forward without reversal or vortex, which was similar to that in a jet in co-flow. Large turbulence intensities occurred around the jet-wake vortex and along sides of the tube wake bifurcation line, therefore the mixing at the low backward inclination angles presented better properties than those at mediate and high backward inclination angles owing to the featured flow structures and turbulence intensities.
Recent meta-analyses of resting-state networks in major depressive disorder (MDD) implicate network disruptions underlying cognitive and affective features of illness. Heterogeneity of findings to date may stem from the relative lack of data parsing clinical features of MDD such as phase of illness and the burden of multiple episodes.
Resting-state functional magnetic resonance imaging data were collected from 17 active MDD and 34 remitted MDD patients, and 26 healthy controls (HCs) across two sites. Participants were medication-free and further subdivided into those with single v. multiple episodes to examine disease burden. Seed-based connectivity using the posterior cingulate cortex (PCC) seed to probe the default mode network as well as the amygdala and subgenual anterior cingulate cortex (sgACC) seeds to probe the salience network (SN) were conducted.
Young adults with remitted MDD demonstrated hyperconnectivity of the left PCC to the left inferior frontal gyrus and of the left sgACC to the right ventromedial prefrontal cortex (PFC) and left hippocampus compared with HCs. Episode-independent effects were observed between the left PCC and the right dorsolateral PFC, as well as between the left amygdala and right insula and caudate, whereas the burden of multiple episodes was associated with hypoconnectivity of the left PCC to multiple cognitive control regions as well as hypoconnectivity of the amygdala to large portions of the SN.
This is the first study of a homogeneous sample of unmedicated young adults with a history of adolescent-onset MDD illustrating brain-based episodic features of illness.
The Helicon-Cathode(HelCat) device is a medium-size linear experiment suitable for a wide range of basic plasma science experiments in areas such as electrostatic turbulence and transport, magnetic relaxation, and high power microwave (HPM)-plasma interactions. The HelCat device is based on dual plasma sources located at opposite ends of the 4 m long vacuum chamber – an RF helicon source at one end and a thermionic cathode at the other. Thirteen coils provide an axial magnetic field B ⩾ 0.220 T that can be configured individually to give various magnetic configurations (e.g. solenoid, mirror, cusp). Additional plasma sources, such as a compact coaxial plasma gun, are also utilized in some experiments, and can be located either along the chamber for perpendicular (to the background magnetic field) plasma injection, or at one of the ends for parallel injection. Using the multiple plasma sources, a wide range of plasma parameters can be obtained. Here, the HelCat device is described in detail and some examples of results from previous and ongoing experiments are given. Additionally, examples of planned experiments and device modifications are also discussed.
The growth of the size of cache and the number of processor cores in modern CPUs is the major factor in advancing the computing performance of modern machines. The effect of CPU cache size in multicore computers on performance, however, has attracted little attention in lubrication and engineering analyses. In this study, the effect of cache size on the computational performance of two parallel iterative methods in solving two Reynolds equations is examined. Four computers, with CPU cache size from 4 to 40 MB and the number of processor cores from 4 to 16, were used. The sizes of the numerical grid were selected to simulate large gridwork (256 × 256) to small gridwork (2048 × 2048) tasks. It is found that the size of CPU cache is a major factor influencing the parallel efficiency in using the RBSOR method. On the other hand, the SPSOR method obtains much higher parallel efficiency than the RBSOR for medium-grained tasks, regardless of the size of CPU cache. The use of the SPSOR can, therefore, provide a much better parallel computing performance than the RBSOR in the cases of having a large number of grids or in a system with limited CPU cache.
The influences of acoustic excitation on the velocity field and mixing characteristic of a jet in cross-flow were investigated in a wind tunnel. The acoustic excitation waves at resonance Strouhal number were generated by a loudspeaker. The time-averaged velocity field and streamlines of the excited elevated transverse jet in the symmetry plane were measured by a high-speed particle image velocimetry. The visual penetration height and spread width were obtained by using an image processing technique. The dispersion characteristics were obtained from the tracer-gas concentration measurement. The results showed that the streamline pattern of the non-excited transverse jet was significantly modified by the acoustic excitation—the bent streamlines evolved from the jet exit escalated and the vortex rings in the jet and tube wakes and the recirculation bubble in the jet wake disappeared. The time-averaged velocity distributions revealed that the excited transverse jet produces large momentum in the up-shooting direction so that the velocity trajectories were located at levels higher than those of the non-excited one. The mixing characteristics, which include the visual penetration height, spread width, and dispersion, were drastically improved by the acoustic excitation due to the changes in the flow structures. The excited transverse jet characterized at larger jet-to-crossflow momentum flux ratios presented larger improvement in the mixing characteristics than at lower jet-to-crossflow momentum flux ratios.
To investigate predictive factors of complete obliteration following treatment with linac-based stereotactic radiosurgery for intracerebral arteriovenous malformations.
Archived plans for 48 patients treated at the British Columbia Cancer Agency and who underwent post-treatment digital subtraction angiography to assess obliteration were studied. Actuarial estimates of obliteration were calculated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards models were used for analysis of incidence of obliteration. Log-rank test was used to search for parameters associated with obliteration.
Complete nidus obliteration was achieved in 38/48 patients (79.2%). Actuarial rate of obliteration was 75.9% at 4 years (95% confidence interval 63.1%-88.6%). On univariate analysis, prescribed dose to the margin (p=0.002) and dose to isocentre (p=0.022) showed statistical significance. No parameters were significant in a multivariate model. According to the log-rank test, prescribed dose to the margin of >20 Gy (p=0.004) and dose to the isocentre of >25 Gy (p=0.004) were associated with obliteration.
Reported series in the literature suggest a number of different factors are predictive of complete obliteration of arteriovenous malformations following radiosurgery. However, differing definitions of volume and complete obliteration makes direct comparison between series difficult. This study demonstrates that complete obliteration of the nidus following linear accelerator-based stereotactic radiosurgery for arteriovenous malformations appears to be most closely related to the prescribed marginal dose. In particular, a marginal dose of >20Gy is strongly associated with obtaining complete obliteration of the nidus.
The beam position monitors (BPMs) with submicron-level resolution act as the major eyes of storage ring in detecting the position of electron beams and are used for feedback system to guide the beam orbit to the desired track. Compared to major improvements on backend electronics, the physical devices generate and transmit signals had little improvement due to the lack of control on manufacturing processes including all mechanical tolerance requirements. The design started with ANSYS to simulate mechanical deformation. Due to the small size (submillimetre) and complicated assembly of feedthrough structure, it is difficult to achieve 1 % tolerance (submicron) in all aspects including machining and brazing. The smallest tolerance for machining is 5 µ and the overall tolerance will be 30 µm. The influence of the tolerance on mechanical will be shown on time-domain reflectometry measurement. The resulted heat-related issue will also be discussed and addressed since the problem happened at SLAC (private communication with Albert Sheng at Stanford Linear Accelerator Center) and DIAMOND (presented at the RF Button Heating Mini-Workshop at EPAC 2008). Manufacturing steps will be described. The consequence of mismatch on manufacturing will be discussed. All related measurement and simulation data are presented in this paper.
Taiwan Photon Source is a new 3-GeV ring with characteristics of great brightness and small emittance, at present under construction at National Synchrotron Radiation Research Center (NSRRC) site in Taiwan and due to be commissioned in 2013. The positioning of the magnets is highly sensitive to alignment errors, and the entire building will be constructed half underground at depth 12 m relative to Taiwan Light Source (TLS) for stability reasons; for these reasons the survey and alignment work is confined and difficult. To position magnets precisely and quickly, a highly accurate auto-tuning girder system combined with a survey network was designed to accomplish the alignment tasks. The survey network includes a preliminary Global Positioning System (GPS) network and a laser-tracking network. The position data from the survey network define a basis for the system of motorized girders to auto-tune and improve the accuracy. The detailed survey and alignment design, simulation and preliminary data are described in this paper.
A precise laser positioning system had been preliminarily developed for the girder system of the Taiwan Photon Source. This laser positioning system, a part of a girder auto-alignment scheme, will be installed on the girders located at both sides of each straight section of the storage ring. The system is composed of a laser and four sets of a position sensing device (PSD). The laser, held on one girder, propagates 13 m along the girder and plays the role of a reference line of girders of the straight section. Based on the laser linear characteristics, the other girder can be adjusted and aligned by a cam mover according to PSD data. To achieve superior precision, the whole laser positioning system should be constructed stably. After making some improvements to eliminate the unstable terms, the precision of the laser positioning system can achieve 2 µm at 13 m propagating distance every 4 h.
Taiwan Photon Source is now under construction at NSRRC Taiwan. In order to maintain the Taiwan Light Source (TLS) for normal operation, a hydrostatic levelling system and precision inclination sensor (Leica Nivel 220) were installed both in the storage ring and beamlines to monitor ground deformation arising. This paper presents the monitoring system setup and the circumstances of ground deformation including vertical settlement and floor inclination during the ground breaking period to provide a criterion for TLS operation.
Taiwan Photon Source (TPS), a new 3 GeV synchrotron ring, is under construction at National Synchrotron Radiation Research Center (NSRRC). To discover problems of design, manufacture and installation, a mockup of 1/24 section (one cell) of TPS was installed at NSRRC. A modified, precise, six-axis, prototype girder system of this mockup composed of three girders was fabricated. We discuss both the installation of the girder system and its diagnostics, and present the results including measurement of the dimensions of the components of the girder system and the vibration tests.
For various medico-legal and financial reasons, some patients may clinically demonstrate an exaggerated hearing loss that varies in degree, nature and laterality. The purpose of this study was to evaluate whether multi-channel auditory steady-state response measurement can be used as an objective test of auditory thresholds in adults with sensorineural hearing loss.
Study design and setting:
This was a prospective, comparative, experimental research design study conducted in an academic medical centre. From January to June 2007, 142 subjects (284 ears) with varying degrees of sensorineural hearing loss were included. Four commonly used frequencies (500, 1000, 2000 and 4000 Hz) were evaluated. Both pure tone thresholds and multi-channel auditory steady-state response thresholds were obtained for each ear in all subjects. The correlation of auditory steady-state response thresholds and pure tone thresholds was assessed. The time taken for multi-channel auditory steady-state response testing was also recorded.
Results for multi-channel auditory steady-state response thresholds and pure tone thresholds were compared for each test frequency. A difference of less than 15 dB was found in 71 per cent of patients, while a difference of less than 20 dB was found in 83 per cent. Correlation between auditory steady-state response thresholds and pure tone thresholds, expressed as the correlation coefficient (r), was 0.89, 0.95, 0.96 and 0.97 at 500, 1000, 2000 and 4000 Hz, respectively. The strength of the relationship between auditory steady-state response thresholds and pure tone thresholds increased with increasing frequency and increasing degree of hearing loss. The recorded auditory steady-state response thresholds were used to calculate regression lines predicting pure tone threshold results. The mean estimated pure tone thresholds calculated from these regression lines were all within 10 dB of the actual recorded pure tone thresholds. The average multi-channel auditory steady-state response test duration was 42 minutes per patient.
Measurement of multi-channel auditory steady-state response could be a powerful, convenient electro-physiological examination with which to objectively certify clinical hearing impairment in adults.
Dental remineralization may be achieved by mediating the interactions between tooth surfaces with free ions and biomimetic peptides. We recently developed octuplet repeats of aspartate-serine-serine (DSS-8) peptide, which occurs in high abundance in naturally occurring proteins that are critical for tooth remineralization. In this paper, we evaluated the possible role of DSS-8 in enamel remineralization. Human enamel specimens were demineralized, exposed briefly to DSS-8 solution, and then exposed to concentrated ionic solutions that favor remineralization. Enamel nano-mechanical behaviors, hardness and elastic modulus, at various stages of treatment were determined by nanoindentation. The phase, microstructure and morphology of the resultant surfaces were characterized using the grazing incidence X-ray diffraction (GIXD), variable pressure scanning electron microscopy (VPSEM), and atomic force microscopy (AFM), respectively. Nanoindentation results show that the DSS-8 remineralization effectively improves the mechanical and elastic properties for demineralized enamel.