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

The Band Excitation Method in Scanning Probe Microscopy for Rapid Mapping of Energy Dissipation on the Nanoscale

Mapping energy transformation pathways and dissipation on the nanoscale and understanding the role of local structure on dissipative behavior is a challenge for imaging in areas ranging from electronics and information technologies to efficient energy production. Here we develop a novel Scanning Probe Microscopy (SPM) technique in which the cantilever is excited and the response is recorded over a band of frequencies simultaneously rather than at a single frequency as in conventional SPMs. This band excitation (BE) SPM allows very rapid acquisition of the full frequency response at each point (i.e. transfer function) in an image and in particular enables the direct measurement of energy dissipation through the determination of the Q-factor of the cantilever-sample system. The BE method is demonstrated for force-distance and voltage spectroscopies and for magnetic dissipation imaging with sensitivity close to the thermomechanical limit. The applicability of BE for various SPMs is analyzed, and the method is expected to be universally applicable to all ambient and liquid SPMs.Comment: 32 pages, 9 figures, accepted for publication in Nanotechnolog

Timescale for equilibration of N/Z gradients in dinuclear systems

Equilibration of N/Z in binary breakup of an excited and transiently deformed projectile-like fragment (PLF*), produced in peripheral collisions of 64Zn + 27Al, 64Zn, 209Bi at E/A = 45 MeV, is examined. The composition of emitted light fragments (3<=Z<=6) changes with the decay angle of the PLF*. The most neutron-rich fragments observed are associated with a small rotation angle. A clear target dependence is observed with the largest initial N/Z correlated with the heavy, neutron-rich target. Using the rotation angle as a clock, we deduce that N/Z equilibration persists for times as long as 3-4 zs (1zs = 1 x 10^-21 s = 300 fm/c). The rate of N/Z equilibration is found to depend on the initial neutron gradient within the PLF*.Comment: 6 pages, 4 figure

Substructure around M31 : Evolution and Effects

We investigate the evolution of a population of 100 dark matter satellites orbiting in the gravitational potential of a realistic model of M31. We find that after 10 Gyr, seven subhalos are completely disrupted by the tidal field of the host galaxy. The remaining satellites suffer heavy mass loss and overall, 75% of the mass initially in the subhalo system is tidally stripped. Not surprisingly, satellites with pericentric radius less than 30 kpc suffer the greatest stripping and leave a complex structure of tails and streams of debris around the host galaxy. Assuming that the most bound particles in each subhalo are kinematic tracers of stars, we find that the halo stellar population resulting from the tidal debris follows an r^{-3.5} density profile at large radii. We construct B-band photometric maps of stars coming from disrupted satellites and find conspicuous features similar both in morphology and brightness to the observed Giant Stream around Andromeda. An assumed star formation efficiency of 5-10% in the simulated satellite galaxies results in good agreement with the number of M31 satellites, the V-band surface brightness distribution, and the brightness of the Giant Stream. During the first 5 Gyr, the bombardment of the satellites heats and thickens the disk by a small amount. At about 5 Gyr, satellite interations induce the formation of a strong bar which, in turn, leads to a significant increase in the velocity dispersion of the disk.Comment: 45 pages, 18 figures. To be submitted to the Astrophysical Journal, version 2.0 : scale height value corrected, references added, and some figures have been modifie

Parametric Self-Oscillation via Resonantly Enhanced Multiwave Mixing

We demonstrate an efficient nonlinear process in which Stokes and anti-Stokes components are generated spontaneously in a Raman-like, near resonant media driven by low power counter-propagating fields. Oscillation of this kind does not require optical cavity and can be viewed as a spontaneous formation of atomic coherence grating

A Systematic Review of Recall Regimen and Maintenance Regimen of Patients with Dental Restorations. Part 2: Implant-Borne Restorations

Purpose To evaluate the current scientific evidence on patient recall and maintenance of implant-supported restorations, to standardize patient care regimens and improve maintenance of oral health. An additional purpose was to examine areas of deficiency in the current scientific literature and provide recommendations for future studies. Materials and Methods An electronic search for articles in the English language literature from the past 10 years was performed independently by multiple investigators using a systematic search process. After application of predetermined inclusion and exclusion criteria, the final list of articles was reviewed to meet the objectives of this review. Results The initial electronic search resulted in 2816 titles. The systematic application of inclusion and exclusion criteria resulted in 14 articles that satisfied the study objectives. An additional 6 articles were added through a supplemental search process for a total of 20 studies. Of these, 11 were randomized controlled clinical trials, and 9 were observational studies. The majority of the studies (15 out of 20) were conducted in the past 5 years and most studies were conducted in Europe (15), followed by Asia (2), South America (1), the United States (1), and the Middle East (1). Results from the qualitative data on a combined 1088 patients indicated that outcome improvements in recall and maintenance regimen were related to (1) patient/treatment characteristic (type of prosthesis, type of prosthetic components, and type of restorative materials); (2) specific oral topical agents or oral hygiene aids (electric toothbrush, interdental brush, chlorhexidine, triclosan, water flossers) and (3) professional intervention (oral hygiene maintenance, and maintenance of the prosthesis). Conclusions There is minimal evidence related to recall regimens in patients with implant-borne removable and fixed restorations; however, a considerable body of evidence indicates that patients with implant-borne removable and fixed restorations require lifelong professional recall regimens to provide biological and mechanical maintenance, customized for each patient. Current evidence also demonstrates that the use of specific oral topical agents and oral hygiene aids can improve professional and at-home maintenance of implant-borne restorations. There is evidence to demonstrate differences in mechanical and biological maintenance needs due to differences in prosthetic materials and designs. Deficiencies in existing evidence compel the forethought of creating clinical practice guidelines for recall and maintenance of patients with implant-borne dental restorations

Impact of Inhibition of Glutamine and Alanine Transport on Cerebellar Glial and Neuronal Metabolism

The cerebellum, or “little brain”, is often overlooked in studies of brain metabolism in favour of the cortex. Despite this, anomalies in cerebellar amino acid homeostasis in a range of disorders have been reported. Amino acid homeostasis is central to metabolism, providing recycling of carbon backbones and ammonia between cell types. Here, we examined the role of cerebellar amino acid transporters in the cycling of glutamine and alanine in guinea pig cerebellar slices by inhibiting amino acid transporters and examining the resultant metabolism of [1-13C]d-glucose and [1,2-13C]acetate by NMR spectroscopy and LCMS. While the lack of specific inhibitors of each transporter makes interpretation difficult, by viewing results from experiments with multiple inhibitors we can draw inferences about the major cell types and transporters involved. In cerebellum, glutamine and alanine transfer is dominated by system A, blockade of which has maximum effect on metabolism, with contributions from System N. Inhibition of neural system A isoform SNAT1 by MeAIB resulted in greatly decreased metabolite pools and reduced net fluxes but showed little effect on fluxes from [1,2-13C]acetate unlike inhibition of SNAT3 and other glutamine transporters by histidine where net fluxes from [1,2-13C]acetate are reduced by ~50%. We interpret the data as further evidence of not one but several glutamate/glutamine exchange pools. The impact of amino acid transport inhibition demonstrates that the cerebellum has tightly coupled cells and that glutamate/glutamine, as well as alanine cycling, play a major role in that part of the brain

Quantitative acoustic models for superfluid circuits

We experimentally realize a highly tunable superfluid oscillator circuit in a quantum gas of ultracold atoms and develop and verify a simple lumped-element description of this circuit. At low oscillator currents, we demonstrate that the circuit is accurately described as a Helmholtz resonator, a fundamental element of acoustic circuits. At larger currents, the breakdown of the Helmholtz regime is heralded by a turbulent shedding of vortices and density waves. Although a simple phase-slip model offers qualitative insights into the circuit's resistive behavior, our results indicate deviations from the phase-slip model. A full understanding of the dissipation in superfluid circuits will thus require the development of empirical models of the turbulent dynamics in this system, as have been developed for classical acoustic systems.Comment: 12 pages, 9 figure