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This double-blind (DB), relapse prevention, phase-3 study was designed to evaluate the efficacy and safety of paliperidone palmitate long-acting 3-monthly formulation (PP3M) versus placebo in delaying time-to-relapse of schizophrenia symptoms.
Methods
Adults (18-70 years old) with schizophrenia (DSM-IV-TR) were treated with PP (17-week, open-label [OL] transition phase: 50, 75, 100, or 150 mg eq, once-monthly, [PP1M]; 12-week OL maintenance phase: 3.5-fold PP1M stabilized dose, single injection), and then randomized (1:1) to PP3M fixed doses (175, 263, 350 or 525 mg eq.) or placebo.
Results
305/506 patients enrolled were randomized (PP3M: n=160; placebo: n=145); majority were men (75%), white (59%), mean age 38.4 years. Interim analysis results favored PP3M vs. placebo (p = 0.0002, two-sided log-rank test; HR: 3.45, 95% CI: 1.73; 6.88); median time-to-relapse was 274 days in placebo and not estimable in PP3M group. Final results were consistent with interim analysis. Both PANSS total score and CGI-S score showed a significant effect over time in PP3M- vs. placebo-treated patients (p>0.001). 330/506 (65.2%) patients in OL phase and 183/305 (60.0%) in DB phase (PP3M: 61.9% vs. placebo: 57.9%) had ≥1 treatment-emergent adverse event (TEAE). The TEAEs noted more frequently in PP3M-vs. placebo (DB phase) were nasopharyngitis (5.6% vs. 1.4%), weight gain (8.8% vs. 3.4%), headache (8.8% vs.4.1%) and akathisia (4.4% vs. 0.7%).
Conclusion
Compared with placebo, PP3M significantly delayed time to first relapse in patients with schizophrenia, previously treated for 4 months with PP1M. PP3M was tolerable with a safety profile generally consistent with other marketed formulations of paliperidone.
The rising need for crop diversification to mitigate the impacts of climate change on food security urges the exploration of crop wild relatives (CWR) as potential genetic resources for crop improvement. This study aimed at assessing the diversity of CWR of the Indian Ocean islands of Mauritius and Rodrigues and proposing cost-effective conservation measures for their sustainable use. A comprehensive list of the native species was collated from The Mauritius Herbarium and published literature. Each species was assessed for the economic value of its related crop, utilization potential for crop improvement, relative distribution, occurrence status and Red List conservation status, using a standard scoring method for prioritization. The occurrence data of the priority species were collected, verified, geo-referenced and mapped. A total of 43 crop-related species were identified for both islands and 21 species were prioritized for active conservation. The CWR diversity hotspots in Mauritius included Mondrain, followed by Florin and Le Pouce Mountain. Although a wide diversity of CWR has been recorded on both islands, most do not relate to major economic crops in use, therefore only a few species may be gene donors to economic crops at the regional and global level. For example, coffee, a major global beverage crop, has three wild relatives on Mauritius, which could potentially be of interest for future predictive characterization.
The observed convective flows on the photosphere (e.g., supergranulation, granulation) play a key role in the Babcock-Leighton (BL) process to generate large scale polar fields from sunspots fields. In most surface flux transport (SFT) and BL dynamo models, the dispersal and migration of surface fields is modeled as an effective turbulent diffusion. We present the first kinematic 3D FT/BL model to explicitly incorporate realistic convective flows based on solar observations. The results obtained are generally in good agreement with the observed surface flux evolution and with non-convective models that have a turbulent diffusivity on the order of 3 × 1012 cm2 s−1 (300 km2 s−1). However, we find that the use of a turbulent diffusivity underestimates the dynamo efficiency, producing weaker mean fields and shorter cycle.
The meridional circulation of the Sun is observationally found to vary with the solar cycle, becoming slower during the solar maxima. We explain this by constructing a theoretical model in which the equation of the meridional circulation (the φ component of the vorticity equation) is coupled with the equations of the flux transport dynamo model. We find that the Lorentz force of the dynamo-generated magnetic fields can slow down the meridional circulation during the solar maxima in broad conformity with the observations.
Optical components such as lenses, glass windows, and prisms are subject to Fresnel reflection due to the mismatch between the refractive indices of the air and glass. An optical interface layer, i.e., antireflection (AR) layer, is needed to eliminate this unwanted reflection at the air/glass interface. Nanostructured broadband and wide-angle AR structures have been developed using a scalable self-assembly process. Ultra-high performance of the nanostructured AR coatings has been demonstrated on various substrates such as quartz, sapphire, polymer, and other materials typically employed in optical lenses. AR coatings on polycarbonate lead to optical transmittance enhancement from approximately 90% to almost 100% for the entire visible, and part of the near-infrared (NIR), band. The AR coatings have also been demonstrated on curved surfaces. AR coatings on n-BK7 lenses enable ultra-high light transmittance for the entire visible, and most of the NIR, spectrum. Nanostructured oxide layers with step-graded index profiles, deposited onto the optical elements of an optical system, can significantly increase sensitivity, and hence improve the overall performance of the system.
This research consists mainly of introducing the hydroarchaeological method, especially as related to issues of drought. The article outlines how this multidisciplinary method can provide insights into the success and failures of an archaeological site, in this case the Maya site of Palenque. We also detail convincing evidence that shows that the Maya of Palenque did not leave their city because of deficiencies of water, as some paleoclimatologists and archaeologists have asserted. The first logical step toward understanding any settlement’s water system is to use basic hydrologic methods and theory and to understand the local watershed. There is great potential for watershed-climate modeling in developing plausible scenarios of water use and supply and of the effect of extreme conditions (flood and drought), all of which cannot be fully represented by atmosphere-based climate and weather projections. The research demonstrates how the local watershed, land-use, and ecological conditions interact with regional climate changes. The archaeological implications for this noninvasive “virtual” method are many, including detecting periods of stress within a community, estimating population by developing caps based on the availability of water, and understanding settlement patterns, as well as assisting present local populations in understanding their water cycle.
Pedigree analysis was used to study the genetic background of 66 Indian early maturing potato selections, the pedigree of which was traced back to 35 ancestors. Six of the 35 contributed 0·42 of the genetic base, which shows the narrow genetic base of Indian early maturing genotypes. Genotypes 2814 (a)1 (f=0·145) and 3069 (d)4 (f=0·145) were the ancestors which appeared most frequently. Based on the coefficient of relationship, the 66 selections were grouped into seven groups with one common ancestor in almost all the selections within a group. The genotypes Kufri Ashoka, Kufri Pukhraj, AGB-69-1, Kufri Jyoti, Kufri Alankar, Kufri Lauvkar and Kufri Kuber were identified as very important parents/ancestors, carrying specific gene complexes valuable in new selections. Crosses between selections from different diversity groups can result in the selection of useful clones while increasing or maintaining genetic diversity, which is desirable to ensure sustainable breeding progress in the future.
The present paper deals with surface enhanced Raman scattering (SERS) study of an organic dye Alizarin Red on colloidal silver nanoparticles. The colloidal solution of nanoparticles is synthesized by pulsed laser ablation of silver rod in pure deionized water using focused out put of 1064nm wavelength of Nd:YAG laser having 35mJ/ pulse energy. Sodium chloride is used as aggregating agents. It is observed that SERS enhancement factor varies strongly depending on concentration of used aggregating agent (especially on the concentration of Cl- ions). These changes in SERS efficiency of colloid are reflected through changes on the absorption spectra. The possible mechanism of SERS is also discussed.
Titanium has proven to be the heat exchanger material of choice for sea-water-cooled power plants owing to its outstanding resistance to pitting and crevice corrosion in a wide range of aggressive media. However, the inertness of the titanium surface makes it highly susceptible to biofilm formation and subsequent biofouling. This can hinder the heat transfer properties and flow of water. Fouling control strategies in condensers include a combination of mechanical, chemical and thermal treatments. However, reports from various industrial situations suggest that mechanical treatment may not have long-term effects. This study aimed to find out whether mechanical cleaning eventually enhances biofilm formation and increases the adherence of biofilm. In our studies epifluorescence micrographs of biofilms on control and mechanically treated titanium surfaces clearly showed accelerated biofilm formation as well as increased adherence on the mechanically cleaned surface. Total counts of viable bacteria acquired by culturing technique, and biofilm thickness measurements made using microscopic techniques, confirmed this observation. Surface profilometry showed increased roughness of the titanium surface, facilitating adherence of biofilm. The number of microbial species was higher on mechanically cleaned and re-exposed surfaces than on fresh titanium. Thus we concluded that mechanical cleaning can increase biofilm formation and adherence of biofilm, thereby increasing the potential of biofouling in the long term.
To evaluate the risk of transmission of SARS coronavirus outside of the health-care setting, close household and community contacts of laboratory-confirmed SARS cases were identified and followed up for clinical and laboratory evidence of SARS infection. Individual- and household-level risk factors for transmission were investigated. Nine persons with serological evidence of SARS infection were identified amongst 212 close contacts of 45 laboratory- confirmed SARS cases (secondary attack rate 4·2%, 95% CI 1·5–7). In this cohort, the average number of secondary infections caused by a single infectious case was 0·2. Two community contacts with laboratory evidence of SARS coronavirus infection had mild or sub-clinical infection, representing 3% (2/65) of Vietnamese SARS cases. There was no evidence of transmission of infection before symptom onset. Physically caring for a symptomatic laboratory-confirmed SARS case was the only independent risk factor for SARS transmission (OR 5·78, 95% CI 1·23–24·24).
Bioactive glasses (6P55) used for coating Ti/Ti-alloy were tested for their in vitro behavior in a comparative study with commercial Bioglass™ (45S5) and commercial Ti alloy (Ti6Al4V). In vitro testing included pH and dissolution rate determination in simulated body fluid (SBF) along with in vitro cyto compatibility testing. It was seen in this work that 6P55 and 45S5 had similar dissolution behavior, demonstrating t½ dependence and maximum pH of approximately 8.1 after 10 days of immersion. This pH was reduce by 0.2 0.4 pH units when the in vitro V:A ratio was increased from 1 to 3. The dissolution rate of these glasses approached 0 after additional immersion tests after 15 days and the pH stablilized at less than 7.5. Cell culture studies showed that both glasses behaved in similar fashion after 16 hours in culture. Both glasses had an increase in cell numbers of close to 200-250%, whereas Ti6Al4V had a less pronounced cell number increase (∼ 180%)
Wafer bonding is an emerging technology for fabrication of complex three-dimensional (3D) structures; particularly it enables monolithic wafer-level 3D integration of high performance, multi-function microelectronic systems. For such a 3D integrated circuits, low-temperature wafer bonding is required to be compatible with the back-end-of-the-line processing conditions. Recently our investigation on surface melting characteristics of copper nanorod arrays showed that the threshold of the morphological changes of the nano-rod arrays occurs at a temperature significantly below the copper bulk melting point. With this unique property of the copper nanorod arrays, wafer bonding using copper nanorod arrays as a bonding intermediate layer was investigated at low temperatures (400 °C and lower). 200 mm Wafers, each with a copper nanorod array layer, were bonded at 200 – 400 °C and with a bonding down-force of 10 kN in a vacuum chamber. Bonding results were evaluated by razor blade test, mechanical grinding and polishing, and cross-section imaging using a focus ion beam/scanning electron microscope (FIB/SEM). The FIB/SEM images show that the copper nanorod arrays fused together accompanying by a grain growth at a bonding temperature of as low as 200 °C. A dense copper bonding layer was achieved at 400 °C where copper grains grew throughout the copper structure and the original bonding interface was eliminated. The sintering of such nanostructures depends not only on their feature size, but also significantly influenced by the bonding pressure. These two factors both contribute to the mass transport in the nanostructure, leading to the formation of a dense bonding layer.