The effects of donepezil in Alzheimer's disease - Results from a multinational trial

Donepezil has been shown to be well tolerated and to improve cognition and global function in patients with mild to moderately severe Alzheimer's disease (AD). The current trial was undertaken to investigate further the efficacy and safety of donepezil, in a multinational setting, in patients with mild to moderately severe AD. This 30-week, placebo-controlled, parallel-group study consisted of a 24-week, double-blind treatment phase followed by a 6-week, single-blind, placebo washout. Eight hundred and eighteen patients with mild to moderately severe AD were randomly allocated to treatment with single, daily doses of 5 or 10 mg donepezil, or placebo. The two primary efficacy measures were: a cognitive performance test, the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and a global evaluation, the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC plus). Secondary outcome measures included the Sum of the Boxes of the Clinical Dementia Rating Scale (CDR-SB), a modified Interview for Deterioration in Daily living activities in Dementia (IDDD) and a patient-rated quality of life assessment. Statistically significant improvements in cognitive and global function were observed, as evaluated by ADAS-cog and CIBIC plus, respectively, in both the 5 and 10 mg/day donepezil groups, compared with placebo. Treatment-associated changes were also observed in functional skills, as shown by improved scores on the CDR-SB and the complex-tasks component of the IDDD. A dose-response effect was evident, with the 10 mg/day donepezil group demonstrating greater benefits in all outcome measures than the 5 mg/day group. Donepezil was well tolerated by this patient population and did not produce any clinically significant laboratory test abnormalities. The results of this study confirm that donepezil is effective and well tolerated in treating the symptoms of mild to moderately severe AD

Sound velocity and absorption measurements under high pressure using picosecond ultrasonics in diamond anvil cell. Application to the stability study of AlPdMn

We report an innovative high pressure method combining the diamond anvil cell device with the technique of picosecond ultrasonics. Such an approach allows to accurately measure sound velocity and attenuation of solids and liquids under pressure of tens of GPa, overcoming all the drawbacks of traditional techniques. The power of this new experimental technique is demonstrated in studies of lattice dynamics, stability domain and relaxation process in a metallic sample, a perfect single-grain AlPdMn quasicrystal, and rare gas, neon and argon. Application to the study of defect-induced lattice stability in AlPdMn up to 30 GPa is proposed. The present work has potential for application in areas ranging from fundamental problems in physics of solid and liquid state, which in turn could be beneficial for various other scientific fields as Earth and planetary science or material research

Tropical and subtropical actinorhizal plants

A maioria dos países tropicais enfrenta dois grandes problemas: o aumento constante da exploração das reservas florestais para extração de madeira ou lenha e a diminuição da fertilidade do solo para produção agrícola. O conceito geral é o de que plantas fixadoras de N2 podem evitar a propalada crise de madeira e alimentos. Juntas com um grande número de leguminosas fixadoras de N2, plantas actinorrízicas podem ter um papel importante na produção de madeira e recuperação de solos. As plantas actinorrízicas compreendem oito famílias de dicotiledôneas, todas elas representadas nos trópicos. Neste trabalho, as mais promissoras plantas actinorrízicas tropicais são brevemente apresentadas e a ênfase é dada principalmente à família Casuarinaceae. Esta família compreende quatro gêneros (Casuarina, Allocasuarina, Gymnostoma e gênero C), com 82 espécies, incluindo muitas árvores que podem produzir madeira de boa qualidade. As estirpes de Frankia que têm sido isoladas das Casuarinaceae crescem lentamente e são capazes de reduzir acetileno in vitro sob ar, o que indica uma capacidade de proteção contra o O2 muito mais eficiente do que no Rhizobium. Apenas as espécies do gênero Casuarina podem ser noduladas pela estirpe ORS 021001, isolada de Casuarina junghuhniana, o que sugere a existência de grupos de inoculação dentro da família Casuarinaceae. A fixação de N2 de Casuarina equisetifolia, crescida em microparcelas de 1 m2, na estação experimental de ORSTM, em Dakar, foi estimada através da comparação do N total em plantas não-inoculadas e plantas inoculadas com a estirpe ORS 021001. Extrapolando para um hectare, a fixação de N2 foi de 131 kg/N em um período de 6,5 meses. Usando o método de equivalência com adubo nitrogenado, a inoculação parece ser equivalente à aplicação de 288 kg de N/ha-1.Most tropical countries face two major problems: increasing overexploitation of wood reserves for timber or fuel wood and diminishing soil fertility for agricultural production. The present consensus is that N2 -fixing plants can help prevent the forthcoming wood and food crisis. Together with the vast group of N2 -fixing Leguminoseae, actinorhizal plants (AP) can play a major role in wood production and land regeneration. AP comprise eight families of dicotyledonous plants all of which are represented in the tropics. In this paper the most promising tropical AP are briefly presented and the emphasis is put mainly on Casuarinaceae. This family forms a group of four genera (Casuarina, Allocasuarina, Gymnostoma and genus C) with 82 species, including many trees that can yield wood of good quality. The Frankia strains that have been isolated from Casuarinaceae grow slowly and are able to reduce acetylene in vitro under air, which indicates that the protection against O2 is much more efficient in Frankia than in rhizobia. Only the species belonging to the Casuarina genus could be nodulated by strain ORS 021001, isolated from Casuarina junghuhniana, suggesting the existence of crossinoculation groups within the family Casuarinaceae. N2 fixation of Casuarina equisetifolia, grown in 1 m2 microplots at the ORSTOM experimental station of Dakar, was estimated by comparing total N in non-inoculated plants and plants inoculated with Frankia strain ORS 021001. Extrapolating to 1 hectare, N2 fixation was 131 kg for a 6.5-month period. Using the N fertilizer equivalence method, inoculation appeared to be equivalent to the application of 288 kg of N fertilizer per hectare

On the Hausdorff volume in sub-Riemannian geometry

For a regular sub-Riemannian manifold we study the Radon-Nikodym derivative of the spherical Hausdorff measure with respect to a smooth volume. We prove that this is the volume of the unit ball in the nilpotent approximation and it is always a continuous function. We then prove that up to dimension 4 it is smooth, while starting from dimension 5, in corank 1 case, it is C^3 (and C^4 on every smooth curve) but in general not C^5. These results answer to a question addressed by Montgomery about the relation between two intrinsic volumes that can be defined in a sub-Riemannian manifold, namely the Popp and the Hausdorff volume. If the nilpotent approximation depends on the point (that may happen starting from dimension 5), then they are not proportional, in general.Comment: Accepted on Calculus and Variations and PD

Newborns' preference for face-relevant stimuli: effects of contrast polarity

There is currently no agreement as to how specific or general are the mechanisms underlying newborns' face preferences. We address this issue by manipulating the contrast polarity of schematic and naturalistic face-related images and assessing the preferences of newborns. We find that for both schematic and naturalistic face images, the contrast polarity is important. Newborns did not show a preference for an upright face-related image unless it was composed of darker areas around the eyes and mouth. This result is consistent with either sensitivity to the shadowed areas of a face with overhead (natural) illumination and/or to the detection of eye contact

Study of the oxygen reduction reaction on pure and Zr-doped YMnO3+δ SOFC electrode

The effect of Zr-doping on the novel SOFC cathode YMnO3 and its O2-Reduction Reaction (ORR) was studied using electrochemical impedance spectroscopy (EIS) as a function of temperature (500 < T < 800 °C) and the oxygen partial pressure (10−4 < pO2 < 1 atm). EIS technique allows identifying three processes controlling the ORR for each electrode, differentiated by their characteristic frequency, activation energies and pO2 dependence. High frequency contribution, only observed at 600°C for both electrodes, was attributed to oxygen ion transfer trough the electrode/electrolyte interface. In both electrodes, the Intermediate frequency contribution was described by a Gerischer impedance, related to a co-limiting process between oxygen ion diffusion and a surface process. However, whereas the EIS characteristics for YMnO3 can be explained by a surface process controlled by the electron transfer from oxide to O-adsorbed, it seems related for Y0.9Zr0.1MnO3 to the probability of finding a second free-surface site near to a diatomic intermediated for the O2 dissociation. These differences are in agreement with the improvement of the electrical properties when YMnO3 is doped with Zr. The low frequency contribution became important as pO2 decreased and temperature increased, and its characteristics would indicate a secondary surface process, co-limited with O2 gas diffusion for Y0.9Zr0.1MnO3 porous electrode.Fil: Moreno Botello, Zulma L.. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Universidad Industrial Santander; ColombiaFil: Montenegro Hernández, Alejandra. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Bariloche | Comision Nacional de Energia Atomica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Bariloche.; ArgentinaFil: Mogni, Liliana Verónica. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Bariloche | Comision Nacional de Energia Atomica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Bariloche.; ArgentinaFil: Gauthier, Gilles H.. Universidad Industrial Santander; Colombi

Nonlinear software sensor for monitoring genetic regulation processes with noise and modeling errors

Nonlinear control techniques by means of a software sensor that are commonly used in chemical engineering could be also applied to genetic regulation processes. We provide here a realistic formulation of this procedure by introducing an additive white Gaussian noise, which is usually found in experimental data. Besides, we include model errors, meaning that we assume we do not know the nonlinear regulation function of the process. In order to illustrate this procedure, we employ the Goodwin dynamics of the concentrations [B.C. Goodwin, Temporal Oscillations in Cells, (Academic Press, New York, 1963)] in the simple form recently applied to single gene systems and some operon cases [H. De Jong, J. Comp. Biol. 9, 67 (2002)], which involves the dynamics of the mRNA, given protein, and metabolite concentrations. Further, we present results for a three gene case in co-regulated sets of transcription units as they occur in prokaryotes. However, instead of considering their full dynamics, we use only the data of the metabolites and a designed software sensor. We also show, more generally, that it is possible to rebuild the complete set of nonmeasured concentrations despite the uncertainties in the regulation function or, even more, in the case of not knowing the mRNA dynamics. In addition, the rebuilding of concentrations is not affected by the perturbation due to the additive white Gaussian noise and also we managed to filter the noisy output of the biological systemComment: 21 pages, 7 figures; also selected in vjbio of August 2005; this version corrects a misorder in the last three references of the published versio

Assessment of the potential in vivo ecotoxicity of Double-Walled Carbon Nanotubes (DWNTs) in water, using the amphibian Ambystoma mexicanum

Because of their specific properties (mechanical, electrical, etc), carbon nanotubes (CNTs) are being assessed for inclusion in many manufactured products. Due to their massive production and number of potential applications, the impact of CNTs on the environment must be taken into consideration. The present investigation evaluates the ecotoxic potential of CNTs in the amphibian larvae (Ambystoma mexicanum). Acute toxicity and genotoxicity were analysed after 12 days of exposure in laboratory conditions. The genotoxic effects were analysed by scoring the micronucleated erythrocytes in the circulating blood of the larvae according to the French standard micronucleus assay. The results obtained in the present study demonstrated that CNTs are neither acutely toxic nor genotoxic to larvae whatever the CNTs concentration in the water, although black masses of CNTs were observed inside the gut. In the increasing economical context of CNTs, complementary studies must be undertaken, especially including mechanistic and environmental investigations

Polarization instabilities in a two-photon laser

We describe the operating characteristics of a new type of quantum oscillator that is based on a two-photon stimulated emission process. This two-photon laser consists of spin-polarized and laser-driven $^{39}$K atoms placed in a high-finesse transverse-mode-degenerate optical resonator, and produces a beam with a power of $\sim$0.2 $\mu$W at a wavelength of 770 nm. We observe complex dynamical instabilities of the state of polarization of the two-photon laser, which are made possible by the atomic Zeeman degeneracy. We conjecture that the laser could emit polarization-entangled twin beams if this degeneracy is lifted.Comment: Accepted by Physical Review Letters. REVTeX 4 pages, 4 EPS figure