Donepezil for the symptomatic treatment of patients with mild to moderate Alzheimer's disease: a meta-analysis of individual patient data from randomised controlled trials

Background: The objective was to evaluate the efficacy and tolerability of donepezil (5 and 10 mg/day) compared with placebo in alleviating manifestations of mild to moderate Alzheimer's disease (AD). Method: A systematic review of individual patient data from Phase II and III double-blind, randomised, placebo-controlled studies of up to 24 weeks and completed by 20 December 1999. The main outcome measures were the ADAS-cog, the CIBIC-plus, and reports of adverse events. Results: A total of 2376 patients from ten trials were randomised to either donepezil 5 mg/day (n = 821), 10 mg/day (n = 662) or placebo (n = 893). Cognitive performance was better in patients receiving donepezil than in patients receiving placebo. At 12 weeks the differences in ADAS-cog scores were 5 mg/day-placebo: - 2.1 [95% confidence interval (CI), - 2.6 to - 1.6; p < 0.001], 10 mg/day-placebo: - 2.5 ( - 3.1 to - 2.0; p < 0.001). The corresponding results at 24 weeks were - 2.0 ( - 2.7 to - 1.3; p < 0.001) and - 3.1 ( - 3.9 to - 2.4; p < 0.001). The difference between the 5 and 10 mg/day doses was significant at 24 weeks (p = 0.005). The odds ratios (OR) of improvement on the CIBIC-plus at 12 weeks were: 5 mg/day-placebo 1.8 (1.5 to 2.1; p < 0.001), 10 mg/day-placebo 1.9 (1.5 to 2.4; p < 0.001). The corresponding values at 24 weeks were 1.9 (1.5 to 2.4; p = 0.001) and 2.1 (1.6 to 2.8; p < 0.001). Donepezil was well tolerated; adverse events were cholinergic in nature and generally of mild severity and brief in duration. Conclusion: Donepezil (5 and 10 mg/day) provides meaningful benefits in alleviating deficits in cognitive and clinician-rated global function in AD patients relative to placebo. Increased improvements in cognition were indicated for the higher dose. Copyright © 2004 John Wiley & Sons, Ltd.

A simple two-stage design for quantitative responses with application to a study in diabetic neuropathic pain

Two-stage designs offer substantial advantages for early phase II studies. The interim analysis following the first stage allows the study to he stopped for futility, or more positively, it might lead to early progression to the trials needed for late phase H and phase III. If the study is to continue to its second stage, then there is an opportunity for a revision of the total sample size. Two-stage designs have been implemented widely in oncology studies in which there is a single treatment arm and patient responses are binary. In this paper the case of two-arm comparative studies in which responses are quantitative is considered. This setting is common in therapeutic areas other than oncology. It will be assumed that observations are normally distributed, but that there is some doubt concerning their standard deviation, motivating the need for sample size review. The work reported has been motivated by a study in diabetic neuropathic pain, and the development of the design for that trial is described in detail. Copyright (C) 2008 John Wiley & Sons, Ltd.

Modeling cumulative evidence for freedom from disease with applications to BSE surveillance trials

This investigation deals with the question of when a particular population can be considered to be disease-free. The motivation is the case of BSE where specific birth cohorts may present distinct disease-free subpopulations. The specific objective is to develop a statistical approach suitable for documenting freedom of disease, in particular, freedom from BSE in birth cohorts. The approach is based upon a geometric waiting time distribution for the occurrence of positive surveillance results and formalizes the relationship between design prevalence, cumulative sample size and statistical power. The simple geometric waiting time model is further modified to account for the diagnostic sensitivity and specificity associated with the detection of disease. This is exemplified for BSE using two different models for the diagnostic sensitivity. The model is furthermore modified in such a way that a set of different values for the design prevalence in the surveillance streams can be accommodated (prevalence heterogeneity) and a general expression for the power function is developed. For illustration, numerical results for BSE suggest that currently (data status September 2004) a birth cohort of Danish cattle born after March 1999 is free from BSE with probability (power) of 0.8746 or 0.8509, depending on the choice of a model for the diagnostic sensitivity.

Metalloestrogens: an emerging class of inorganic xenoestrogens with potential to add to the oestrogenic burden of the human breast

Many compounds in the environment have been shown capable of binding to cellular oestrogen receptors and then mimicking the actions of physiological oestrogens. The widespread origin and diversity in chemical structure of these environmental oestrogens is extensive but to date such compounds have been organic and in particular phenolic or carbon ring structures of varying structural complexity. Recent reports of the ability of certain metal ions to also bind to oestrogen receptors and to give rise to oestrogen agonist responses in vitro and in vivo has resulted in the realisation that environmental oestrogens can also be inorganic and such xenoestrogens have been termed metalloestrogens. This report highlights studies which show metalloestrogens to include aluminium, antimony, arsenite, barium, cadmium, chromium (Cr(II)), cobalt, copper, lead, mercury, nickel, selenite, tin and vanadate. The potential for these metal ions to add to the burden of aberrant oestrogen signalling within the human breast is discussed. Copyright (c) 2006 John Wiley & Sons, Ltd.

Growth rate and physical properties of Erythrina variegata with regard to dry matter production

Erythrina variegata grown from seeds showed a great deal of variation with respect to height, diameter, density of wood and dry matter production. Statistical analysis showed that the density of wood produced by any plant was not related to its growth rate, but dry matter production was associated with plant growth rate (height and diameter) that could lead to overall increased dry matter or biomass production.

Disparity with respect to a local reference plane as a dominant cue for stereoscopic depth relief

Earlier studies showed that the disparity with respect to other visible points could not explain stereoacuity performance, nor could various spatial derivatives of disparity [Glennerster, A., McKee, S. P., & Birch, M. D. (2002). Evidence of surface-based processing of binocular disparity. Current Biology, 12:825-828; Petrov, Y., & Glennerster, A. (2004). The role of the local reference in stereoscopic detection of depth relief. Vision Research, 44:367-376.] Two possible cues remain: (i) local changes in disparity gradient or (ii) disparity with respect to an interpolated line drawn through the reference points. Here, we aimed to distinguish between these two cues. Subjects judged.. in a two AFC paradigm, whether a target dot was in front of a plane defined by three reference dots or, in other experiments, in front of a line defined by two reference dots. We tested different slants of the reference line or plane and different locations of the target relative to the reference points. For slanted reference lines or plane, stereoacuity changed little as the target position was varied. For judgments relative to a frontoparallel reference line, stereoacuity did vary with target position, but less than would be predicted by disparity gradient change. This provides evidence that disparity with respect to the reference plane is an important cue. We discuss the potential advantages of this measure in generating a representation of surface relief that is invariant to viewpoint transformations. (c) 2006 Elsevier Ltd. All rights reserved.

A Packet/Frame sync detector based on statistical mode with application to wireless-USB

Wireless Personal Area Networks (WPANs) are offering high data rates suitable for interconnecting high bandwidth personal consumer devices (Wireless HD streaming, Wireless-USB and Bluetooth EDR). ECMA-368 is the Physical (PHY) and Media Access Control (MAC) backbone of many of these wireless devices. WPAN devices tend to operate in an ad-hoc based network and therefore it is important to successfully latch onto the network and become part of one of the available piconets. This paper presents a new algorithm for detecting the Packet/Fame Sync (PFS) signal in ECMA-368 to identify piconets and aid symbol timing. The algorithm is based on correlating the received PFS symbols with the expected locally stored symbols over the 24 or 12 PFS symbols, but selecting the likely TFC based on the highest statistical mode from the 24 or 12 best correlation results. The results are very favorable showing an improvement margin in the order of 11.5dB in reference sensitivity tests between the required performance using this algorithm and the performance of comparable systems.

Different splitting techniques with application to air pollution models

Splitting techniques are commonly used when large-scale models, which appear in different fields of science and engineering, are treated numerically. Four types of splitting procedures are defined and discussed. The problem of the choice of a splitting procedure is investigated. Several numerical tests, by which the influence of the splitting errors on the accuracy of the results is studied, are given. It is shown that the splitting errors decrease linearly when (1) the splitting procedure is of first order and (2) the splitting errors are dominant. Three examples for splitting procedures used in all large-scale air pollution models are presented. Numerical results obtained by a particular air pollution model, Unified Danish Eulerian Model (UNI-DEM), are given and analysed.

A parallel convolutional coder including embedded puncturing with application to consumer devices

As consumers demand more functionality) from their electronic devices and manufacturers supply the demand then electrical power and clock requirements tend to increase, however reassessing system architecture can fortunately lead to suitable counter reductions. To maintain low clock rates and therefore reduce electrical power, this paper presents a parallel convolutional coder for the transmit side in many wireless consumer devices. The coder accepts a parallel data input and directly computes punctured convolutional codes without the need for a separate puncturing operation while the coded bits are available at the output of the coder in a parallel fashion. Also as the computation is in parallel then the coder can be clocked at 7 times slower than the conventional shift-register based convolutional coder (using DVB 7/8 rate). The presented coder is directly relevant to the design of modern low-power consumer devices

Mining gene networks with application to GAW15 problem 1

The genetic analysis workshop 15 (GAW15) problem 1 contained baseline expression levels of 8793 genes in immortalised B cells from 194 individuals in 14 Centre d’Etude du Polymorphisme Humane (CEPH) Utah pedigrees. Previous analysis of the data showed linkage and association and evidence of substantial individual variations. In particular, correlation was examined on expression levels of 31 genes and 25 target genes corresponding to two master regulatory regions. In this analysis, we apply Bayesian network analysis to gain further insight into these findings. We identify strong dependences and therefore provide additional insight into the underlying relationships between the genes involved. More generally, the approach is expected to be applicable for integrated analysis of genes on biological pathways.

Building integration photovoltaic module with reference to Ghana: using triple junction amorphous silicon

This paper assesses the potential for using building integrated photovoltaic (BIPV) roof shingles made from triple-junction amorphous silicon (3a-Si) for electrification and as a roofing material in tropical countries, such as Accra, Ghana. A model roof was constructed using triple-junction amorphous (3a-Si) PV on one section and conventional roofing tiles on the other. The performance of the PV module and tiles were measured, over a range of ambient temperatures and solar irradiance. PVSyst (a computer design software) was used to determine the most appropriate angle of tilt. It was observed that 3a-Si performs well in conditions such as Accra, because it is insensitive to high temperatures. Building integration gives security benefits, and reduces construction costs and embodied energy, compared to freestanding PV systems. Again, it serves as a means of protection from salt spray from the oceans and works well even when shaded. However, compared to conventional roofing materials, 3a-Si would increase the indoor temperature by 1-2 °C depending on the surface area of the roof covered with the PV modules. The results presented in this research enhance the understanding of varying factors involved in the selection of an appropriate method of PV installation to offset the short falls of the conventional roofing material in Ghana.

Measurement of apolipoprotein B-48 in the Svedberg flotation rate (Sf) > 400, Sf 60 – 400 and Sf 20 – 60 lipoprotein fractions reveals novel findings with respect to the effects of dietary fatty acids on triacylglycerol-rich lipoproteins in postmenopausal women

The present study was designed to examine whether the type of fat ingested in an initial test meal influences the response and density distribution of dietary-derived lipoproteins in the Svedberg flotation rate (Sf)>400, Sf 60 - 400 and Sf 20 - 60 lipoprotein fractions. A single-blind randomized within-subject crossover design was used to study the effects of palm oil, safflower oil, a mixture of fish and safflower oil, and olive oil on postprandial apolipoprotein (apo) B-48, retinyl ester and triacylglycerol responses in each lipoprotein fraction following an initial test meal containing one of the oils and a second standardized test meal. For all dietary oils, late postprandial (300min) concentrations of triacylglycerol and apo B-48 were significantly higher in the Sf 60 - 400 fraction than in the Sf>400 fraction (P<0.02). Significantly greater apo B-48 incremental areas under the curve (IAUCs) were also observed in the Sf 60 - 400 fraction than in the Sf>400 fraction following palm oil, safflower oil and olive oil (P<0.04), with a similar non-significant trend for fish/safflower oil. Olive oil resulted in a significantly greater apo B-48 IAUC in the Sf>400 fraction (P<0.02) than did any of the other dietary oils, as well as a tendency for a higher IAUC in the Sf 60 - 400 fraction compared with the palm, safflower and fish/safflower oils. In conclusion, we have found that the majority of intestinally derived lipoproteins present in the circulation following meals enriched with saturated, polyunsaturated or monounsaturated fatty acids are of the density and size of small chylomicrons and chylomicron remnants. Olive oil resulted in a greater apo B-48 response compared with the other dietary oils following sequential test meals, suggesting the formation of a greater number of small (Sf 60 - 400) and large (Sf>400) apo B-48-containing lipoproteins in response to this dietary oil.

Evaluating the response of children with autism to a robot

Since 1998, the Aurora project has been investigating the use of a robotic platform as a tool for therapy use with children with autism. A key issue in this project is the evaluation of the interactions, which are not constricted and involve the child moving freely. Additionally, the response of the children is an important factor which must emerge from the robot trial sessions and the evaluation methodology, in order to guide further development work.