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Quetiapine immediate release (quetiapine IR) improves PANSS total, positive, negative and general psychopathology scores in schizophrenia. This study (D1444C00132) evaluated the efficacy of once-daily extended release quetiapine fumarate (quetiapine XR) in patients with acute schizophrenia.
This was a 6-week, double-blind, randomised study (n=588) comparing quetiapine XR (400, 600 or 800 mg/day) and quetiapine IR (400 mg/day) with placebo. Efficacy was assessed using ANCOVA analyses of the change from baseline to study endpoint (Day 42) for: PANSS total score; positive, negative and general psychopathology subscale scores; and aggression and depression cluster scores (modified ITT population, LOCF). Changes in individual PANSS item scores were assessed post hoc.
At Day 42, there were statistically significant reductions (ie two-sided p-value <0.05) versus placebo with all doses of quetiapine XR for the change in PANSS total, positive, general psychopathology and aggression cluster scores. Changes in negative and depression cluster scores were statistically significant versus placebo for quetiapine XR 600 mg/day and 800 mg/day. There was statistically significant separation from placebo with quetiapine XR 600 mg/day and 800 mg/day for the change in 6/7 PANSS positive items, 5/7 negative items, and 12/16 general psychopathology items. For those items with no statistically significant separation from placebo, baseline scores were generally low.
Once-daily quetiapine XR is effective across a broad range of symptoms in acute schizophrenia, including positive and negative symptoms, as well as symptoms of general psychopathology, aggression and depression.
To evaluate efficacy and tolerability of quetiapine sustained release (SR) in a 6-week study (D1444C00132).
588 patients with acute schizophrenia (PANSS total ≥70; CGI-S ≥4) were randomised to fixed-dose quetiapine SR 400, 600 or 800 mg/day (once-daily), quetiapine immediate release (IR) 400 mg/day (200 mg twice-daily; 5-day dose-escalation schedule), or placebo. Quetiapine SR doses: 400, 600 mg reached by Day 2; 800 mg by Day 3. Primary endpoint: change from baseline to Day 42 in PANSS total score (LOCF; ANCOVA). Other assessments: PANSS response rate (% patients with ≥30% reduction in total score from baseline); CGI-I response rate (% patients with rating ≤3); CGI-S; AEs.
446 patients (76%) completed the study (similar across groups). LS mean change from baseline in PANSS total score at Day 42 showed significant improvement versus placebo (-18.8): -24.8 (p=0.03), -30.9 (p<0.001), and -31.3 (p<0.001), quetiapine SR 400, 600, and 800 mg, respectively; -26.6 (p=0.004), quetiapine IR. Statistical separation from placebo at Day 42 for: change from baseline in CGI-S (quetiapine SR 600 and 800 mg; IR); PANSS and CGI-I response rates (all active treatments). Most common AEs with quetiapine: somnolence and dizziness. There were no unexpected AEs with quetiapine SR. Incidence of EPS-related AEs was similar to placebo. Two quetiapine SR and two IR patients discontinued due to AEs in Week 1.
Once-daily quetiapine SR (400-800 mg) was effective versus placebo in patients with acute schizophrenia. Rapid dose escalation was well tolerated, with a therapeutically effective dose reached by Day 2.
Affective symptomatology has repeatedly been suggested to confer susceptibility to tardive dyskinesia (TD). In our sample of 174 schizophrenic patients a history of depressive symptoms was not associated with the occurrence of TD, whereas manic symptomatology was significantly associated with the absence of TD. Thus, our data suggest that affective symptomatology cannot unambiguously be considered to predispose to TD.
A range of endophenotypes characterise psychosis, however there has been limited work understanding if and how they are inter-related.
This multi-centre study includes 8754 participants: 2212 people with a psychotic disorder, 1487 unaffected relatives of probands, and 5055 healthy controls. We investigated cognition [digit span (N = 3127), block design (N = 5491), and the Rey Auditory Verbal Learning Test (N = 3543)], electrophysiology [P300 amplitude and latency (N = 1102)], and neuroanatomy [lateral ventricular volume (N = 1721)]. We used linear regression to assess the interrelationships between endophenotypes.
The P300 amplitude and latency were not associated (regression coef. −0.06, 95% CI −0.12 to 0.01, p = 0.060), and P300 amplitude was positively associated with block design (coef. 0.19, 95% CI 0.10–0.28, p < 0.001). There was no evidence of associations between lateral ventricular volume and the other measures (all p > 0.38). All the cognitive endophenotypes were associated with each other in the expected directions (all p < 0.001). Lastly, the relationships between pairs of endophenotypes were consistent in all three participant groups, differing for some of the cognitive pairings only in the strengths of the relationships.
The P300 amplitude and latency are independent endophenotypes; the former indexing spatial visualisation and working memory, and the latter is hypothesised to index basic processing speed. Individuals with psychotic illnesses, their unaffected relatives, and healthy controls all show similar patterns of associations between endophenotypes, endorsing the theory of a continuum of psychosis liability across the population.
A number of laser facilities coming online all over the world promise the capability of high-power laser experiments with shot repetition rates between 1 and 10 Hz. Target availability and technical issues related to the interaction environment could become a bottleneck for the exploitation of such facilities. In this paper, we report on target needs for three different classes of experiments: dynamic compression physics, electron transport and isochoric heating, and laser-driven particle and radiation sources. We also review some of the most challenging issues in target fabrication and high repetition rate operation. Finally, we discuss current target supply strategies and future perspectives to establish a sustainable target provision infrastructure for advanced laser facilities.
Data on gender-specific profiles of cognitive functions in patients with Parkinson's disease (PD) are rare and inconsistent, and possible disease-confounding factors have been insufficiently considered.
The LANDSCAPE study on cognition in PD enrolled 656 PD patients (267 without cognitive impairment, 66% male; 292 with mild cognitive impairment, 69% male; 97 with PD dementia, 69% male). Raw values and age-, education-, and gender-corrected Z scores of a neuropsychological test battery (CERAD-Plus) were compared between genders. Motor symptoms, disease duration, l-dopa equivalent daily dose, depression - and additionally age and education for the raw value analysis - were taken as covariates.
Raw-score analysis replicated results of previous studies in that female PD patients were superior in verbal memory (word list learning, p = 0.02; recall, p = 0.03), while men outperformed women in visuoconstruction (p = 0.002) and figural memory (p = 0.005). In contrast, gender-corrected Z scores showed that men were superior in verbal memory (word list learning, p = 0.02; recall, p = 0.02; recognition, p = 0.04), while no difference was found for visuospatial tests. This picture could be observed both in the overall analysis of PD patients as well as in a differentiated group analysis.
Normative data corrected for gender and other sociodemographic variables are relevant, since they may elucidate a markedly different cognitive profile compared to raw scores. Our study also suggests that verbal memory decline is stronger in women than in men with PD. Future studies are needed to replicate these findings, examine the progression of gender-specific cognitive decline in PD and define different underlying mechanisms of this dysfunction.
The formation and evolution of hydrogen- and vacancy-related donor and acceptor states were studied in helium-implanted and subsequently hydrogen plasma-treated n-type Float-Zone (FZ) silicon wafers by means of two-point-probe Spreading Resistance (SR) measurements. He+-implantation was executed at 3.75 MeV and 11 MeV at fluences of 1×1014 cm−2. Post-implantation 13.56-MHz RF-plasma hydrogenations were carried out at 150 W either for 15 min or 1 hour, applying substrate temperatures between 350 °C and 500 °C. Enhanced donor concentrations as well as acceptor-like states were observed in the subsurface layers of the treated FZ Si samples after 15-min post-implantation H-plasma exposures. Under appropriate process conditions, the latter ones compensated for the n-type doping, so that even buried p-type layers were created. The experimental results indicated that oxygen played a central role in the formation of the acceptor-like states.
An on-farm trial was conducted in the northern Guinea savanna of Nigeria, over a period of five years, with the objectives of quantifying the effects on maize of applying cattle manure in combination with synthetic fertilizer with regard to soil characteristics, yield, plant nutrition and profitability. Maize grain yield was significantly increased by the annual application of cattle manure, compared to maize receiving an equal amount of N through synthetic fertilizer, but only from the third year of the experiment. The application of manure resulted in higher soil Kjel N, Bray-I P and exchangeable K values, and an increased N utilization efficiency by maize, suggesting that yield-limiting factors other than N deficiencies were of lesser importance than in the treatment receiving sole inorganic fertilizer. Nutrients other than N applied via the manure, particularly P, K and/or B, may have contributed to the higher grain yields in treatments receiving manure. A partial budgeting analysis revealed that, over a 5-year period, investments in the application of manure, in combination with synthetic fertilizer, resulted in higher margins than the application of fertilizer alone. However, analyses of marginal rates of return of changes from low urea N to high urea N or additional manure applications suggested that it was more profitable to invest in additional urea than in organic manure in the first two years of the experiment. The results suggested that manure applications, even when applied at relatively high rates, did not serve as a quick fix to on-farm soil fertility problems, but over a longer period, manure applied in combination with synthetic fertilizers did provide a significant and profitable contribution to enhanced cereal production.
This paper presents some of the highly modern and innovative solutions
used by VOEST-ALPINE Industrieanlagenbau (VAI) to comply with the high quality
and productivity requirements set for the stainless steel slab continuous casting
machine supplied to the Tornio plant of Outokumpu Oy and started up in September 2002.
In November 2000, UGINE&ALZ Genk awarded VAI a contract to upgrade their
steelmaking plant. The scope of work included the world's largest stainless steel slab
caster designed for an annual output of 1.2 million tons. The existing casting machine
had to be replaced within a comprehensive shut-down period of 21 days only to minimize
the financial burden due to the production outage. Innovative project management solutions
combined with excellent realization resulted in a successful start-up on October 1, 2002,
after a shutdown period of only 20 days. Operational results with regard to productivity
and quality are discussed.
This paper describes the equipments and systems, designed and supplied
by VOEST-ALPINE Industrieanlagenbau (VAI), for the extension of the stainless
steel production plant of Ugine & ALZ at Genk. The main results obtained during
the first year of full operation of this modernized plant are presented.
Two particularly important reliability issues facing the integration of low-
κ dielectric films are the fracture energy of the barrier-dielectric
interface and the barrier layer integrity during processing. We have noticed
that the compressive stresses in the barrier layers on low- κ dielectrics
lead to spontaneous delamination and formation of telephone-cord like
morphologies. These morphologies allow the measurement of fracture energy
and are advantageous over artificially contrived features to yield realistic
debonding parameters. The fracture energy of common barrier films, TaN and
Ta, was determined using this method for varying porosity nanoporous silica
and MSQ. Detailed characterization of the telephone cord morphology using a
combination of Optical Microscopy, SEM and Profilometry was done. The
fracture energy for Ta on different low-κ dielectrics was evaluated using a
1-D model for straight buckles. The kinetic coefficient of buckling was also
The damage induced in the low-k material upon exposure to dry etch and ash
plasmas is a point of major concern in terms of preservation of the
dielectric properties. There is urgent need to assess, classify and quantify
the extent of such damage to allow the optimization of patterning processes
and conditions. Meander-fork structures with spacings between 250nm and 70nm
are used in this study as vehicle to compare trends in electrical
performance for different dielectrics: SiO2 and two SiOC:H low-k
materials with pristine k values of 3.0 and 2.6. Here we demonstrate that
the ‘electrical equivalent damage’ model is a valid and precise methodology
for assessing dielectric damage upon processing from interline capacitance
evaluation. This analysis allows to distinguish between bulk and sidewall
modification and to quantify the extent of damage. Moreover, it provides an
interpretation for the degradation of leakage current and breakdown field of
the interline dielectric, revealing different trends whether due to only
sidewall or total damage.
Vertical and in-plane electrical transport in InAs/InP semiconductors wires and dots have been investigated by conductive atomic force microscopy (C-AFM) and electrical measurements in processed devices. Localized I-V spectroscopy and spatially resolved current images (at constant bias), carried out using C-AFM in a controlled atmosphere at room temperature, show different conductances and threshold voltages for current onset on the two types of nanostructures. The processed devices were used in order to access the in-plane conductance of an assembly with a reduced number of nanostructures. On these devices, signature of two-level random telegraph noise (RTN) in the current behavior with time at constant bias is observed. These levels for electrical current can be associated to electrons removed from the wetting layer and trapped in dots and/or wires. A crossover from conduction through the continuum, associated to the wetting layer, to hopping within the nanostructures is observed with increasing temperature. This transport regime transition is confirmed by a “temperature-voltage” phase diagram.
This paper describes various technological packages developed and implemented
by VAI to help steel companies raise product quality, increase reliability and lower
operating and maintenance costs for slab and bloom continuous casters.
On-farm trials were conducted in the northern Guinea savanna of Nigeria. The objective was to compare integrated Striga hermonthica control measures (soyabean or cowpea trap crop in the first year followed by maize resistant to Striga in the second year) with farmers' traditional practices (cereal-based cropping systems) under farmer-managed conditions.
Integrated control proved to be highly effective in terms of reducing Striga incidence both in terms of reduced seed density in the soil and decreased infection in maize. Resistant maize following the soyabean trap crop yielded 1.58 t ha−1 of grain and out-yielded local maize following traditional practices by more than 80%. Similarly, the overall productivity over the period of the experiment was highest with the integrated control treatment using soyabean. Conversely, resistant maize after the cowpea trap crop yielded only 0.92 t ha−1 (possibly due to the poor performance of the cowpea crop in the first year), and maize yields were similar to those obtained with farmer practices. Initial Striga seed density in the soil was negatively correlated (r = −0.33) with soil nitrogen, but nitrogen-fertilizer application rates did not seem to affect the level of Striga infection in maize.
Vibrational properties of self-assembled InAs quantum dots (QD’s) embedded in AlAs and aluminium oxide were studied by Raman spectroscopy. The InAs/AlAs QD structures were grown by molecular beam epitaxy on GaAs (001) substrates. The following main features of the phonon spectra of InAs/AlAs QD nanostructures were observed: 1) asymmetric lines of QD LO phonons affected by strain, confinement and size inhomogeneity of QD’s; 2) confined phonons of InAs wetting layer (WL); 3) two bands of interface phonons in the AlAs frequency region, attributed to modes associated with the planar interface WL/AlAs matrix and the three-dimensional QD/matrix interface; 4) doublets of folded acoustic phonons caused by periodicity in the multilayer QD structures. The influence of growth temperature, varied from 420 to 550°C, on the morphology of QD’s was investigated. QD’s grown at 420°C are found to have the smallest size. Increasing the temperature up to 480°C leads to the formation of larger InAs islands and improved size homogeneity. Further temperature elevation (above 500°C) causes partial re-evaporation of InAs leading to a decrease of QD size and density, and, finally, their complete disappearance. InAs QD’s embedded in aluminium oxide were fabricated by selective oxidation of the AlAs matrix in self-assembled InAs/AlAs QD’s. Micro-Raman spectroscopy data show that depending on oxidation conditions (humidity, temperature) InAs QD’s in an oxide matrix can be even more strained than before oxidation, or become fully relaxed. At the boundaries of oxidized/non-oxidized areas the presence of amorphous and crystalline As clusters is evident.