Effect of apolipoprotein E and butyrylcholinesterase genotypes on cognitive response to cholinesterase inhibitor treatment at different stages of Alzheimer's disease

Factors that influence response to drug treatment are of increasing importance. We report an analysis of genetic factors affecting response to cholinesterase inhibitor therapy in 165 subjects with Alzheimer's disease (AD). The presence of apolipoprotein E e4 (APOE e4) allele was associated with early and late cognitive response to cholinesterase inhibitor treatment in mild AD (Mini-Mental State Examination (MMSE) greater than or equal to21) (P

Stereotactic radiosurgery for intractable cluster headache: an initial report from the North American Gamma Knife Consortium.

Abstract Object The aim of this study was to evaluate the outcomes of Gamma Knife surgery (GKS) when used for patients with intractable cluster headache (CH). Methods Four participating centers of the North American Gamma Knife Consortium identified 17 patients who underwent GKS for intractable CH between 1996 and 2008. The median patient age was 47 years (range 26-83 years). The median duration of pain before GKS was 10 years (range 1.3-40 years). Seven patients underwent unsuccessful prior surgical procedures, including microvascular decompression (2 patients), microvascular decompression with glycerol rhizotomy (2 patients), deep brain stimulation (1 patient), trigeminal ganglion stimulation (1 patient), and prior GKS (1 patient). Fourteen patients had associated autonomic symptoms. The radiosurgical target was the trigeminal nerve (TN) root and the sphenopalatine ganglion (SPG) in 8 patients, only the TN in 8 patients, and only the SPG in 1 patient. The median maximum TN and SPG dose was 80 Gy. Results Favorable pain relief (Barrow Neurological Institute Grades I-IIIb) was achieved and maintained in 10 (59%) of 17 patients at a median follow-up of 34 months. Three patients required additional procedures (repeat GKS in 2 patients, hypothalamic deep brain stimulation in 1 patient). Eight (50%) of 16 patients who had their TN irradiated developed facial sensory dysfunction after GKS. Conclusions Gamma Knife surgery for intractable, medically refractory CH provided lasting pain reduction in approximately 60% of patients, but was associated with a significantly greater chance of facial sensory disturbances than GKS used for trigeminal neuralgia.

Learning and organization in the knowledge-based information economy: Initial findings from a participatory action research case study

This paper reports on an ongoing, multiphase, project-based action learning and research project. In particular, it summarizes some aspects of the learning climate and outcomes for a case study company In the software industry, Using a participatory action research approach, the learning company framework developed by Pedler et al, (1997) is used to initiate critical reflection in the company at three levels: managing director, senior management team and technical and professional staff. As such, this is one of the first systematic attempts to apply this framework to the entire organization and to a company in the knowledge-based learning economy. Two sets of issues are of general concern to the company: internal issues surrounding the company's reward and recognition policies and practices and the provision of accounting and control information in a business relevant way to all levels of staff; and external issues concerning the extent to which the company and its members actively learn from other companies and effectively capture, disseminate and use information accessed by staff in boundary-spanning roles. The paper concludes with some illustrations of changes being introduced by the company as a result of the feedback on and discussion of these issues.

Simulation of a collisionless planar electrostatic shock in a proton-electron plasma with a strong initial thermal pressure change

The localized deposition of the energy of a laser pulse, as it ablates a solid target, introduces high thermal pressure gradients in the plasma. The thermal expansion of this laser-heated plasma into the ambient medium (ionized residual gas) triggers the formation of non-linear structures in the collisionless plasma. Here an electron-proton plasma is modelled with a particle-in-cell simulation to reproduce aspects of this plasma expansion. A jump is introduced in the thermal pressure of the plasma, across which the otherwise spatially uniform temperature and density change by a factor of 100. The electrons from the hot plasma expand into the cold one and the charge imbalance drags a beam of cold electrons into the hot plasma. This double layer reduces the electron temperature gradient. The presence of the low-pressure plasma modifies the proton dynamics compared with the plasma expansion into a vacuum. The jump in the thermal pressure develops into a primary shock. The fast protons, which move from the hot into the cold plasma in the form of a beam, give rise to the formation of phase space holes in the electron and proton distributions. The proton phase space holes develop into a secondary shock that thermalizes the beam.

Boost radiosurgery as a strategy after failure of initial management of pediatric primitive neuroectodermal tumors Clinical article

The aim in this study was to determine the outcomes of boost stereotactic radiosurgery, specifically Gamma Knife surgery (GKS), for recurrent primitive neuroectodermal tumors (PNETs) in children in whom initial multimodality management had failed.

Effect of the incorporation of hydroxy-terminated liquid silicones on the cure characteristics, morphology, and release of a model protein from silicone elastomer-covered rods

Silicone elastomer systems have previously been shown to offer potential for the sustained release of protein therapeutics. However, the general requirement for the incorporation of large amounts of release enhancing solid excipients to achieve therapeutically effective release rates from these otherwise hydrophobic polymer systems can detrimentally affect the viscosity of the precure silicone elastomer mixture and its curing characteristics. The increase in viscosity necessitates the use of higher operating pressures in manufacture, resulting in higher shear stresses that are often detrimental to the structural integrity of the incorporated protein. The addition of liquid silicones increases the initial tan delta value and the tan delta values in the early stages of curing by increasing the liquid character (G '') of the silicone elastomer system and reducing its elastic character (G'), thereby reducing the shear stress placed on the formulation during manufacture and minimizing the potential for protein degradation. However, SEM analysis has demonstrated that if the liquid character of the silicone elastomer is too high, the formulation will be unable to fill the mold during manufacture. This study demonstrates that incorporation of liquid hydroxy-terminated polydimethylsiloxanes into addition-cure silicone elastomer-covered rod formulations can both effectively lower the viscosity of the precured silicone elastomer and enhance the release rate of the model therapeutic protein bovine serum albumin. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

Aerospace Stiffened Panel Initial Sizing With Novel Skin Sub-Stiffening Features

The introduction of skin sub-stiffening features has the potential to modify the local stability and fatigue crack growth performance of stiffened panels. Proposed herein is a method to enable initial static strength sizing of panels with such skin sub-stiffening features. The method uses bespoke skin buckling coefficients, automatically generated by Finite Element analysis and thus limits the modification to the conventional aerospace panel initial sizing process. The approach is demonstrated herein and validated for prismatic sub-stiffening features. Moreover, examination of the generated buckling coefficient data illustrates the influence of skin sub-stiffening on buckling behavior, with static strength increases typically corresponding to a reduction in the number of initial skin longitudinal buckle half-waves.

PicSOr - An objective test of perceptual skill that predicts laparoscopic technical skill in three initial studies of laparoscopic performance

Background: Laparoscopic surgery requires surgeons to infer the shape of 3-D structures, such as the internal organs of patients, from 2-D displays on a video monitor. Recent evidence indicates that the issue is not resolved by the use of contemporary 3-D camera systems. It is therefore crucial to find ways of measuring differences in aptitude for recovering 3-D structure from 2-D images, and assessing its impact on performance. Our aim was to test empirically for a relationship between laparoscopic ability and the perceptual skill of recovering information about 3-D structures from 2-D monitor displays.

Estimation of survival rate and extinction probability for stage-structured populations with overlapping life stages

The development of methods providing reliable estimates of demographic parameters (e. g., survival rates, fecundity) for wild populations is essential to better understand the ecology and conservation requirements of individual species. A number of methods exist for estimating the demographics of stage-structured populations, but inherent mathematical complexity often limits their uptake by conservation practitioners. Estimating survival rates for pond-breeding amphibians is further complicated by their complex migratory and reproductive behaviours, often resulting in nonobservable states and successive cohorts of eggs and tadpoles. Here we used comprehensive data on 11 distinct breeding toad populations (Bufo calamita) to clarify and assess the suitability of a relatively simple method [the Kiritani-Nakasuji-Manly (KNM) method] to estimate the survival rates of stage-structured populations with overlapping life stages. The study shows that the KNM method is robust and provides realistic estimates of amphibian egg and larval survival rates for species in which breeding can occur as a single pulse or over a period of several weeks. The study also provides estimates of fecundity for seven distinct toad populations and indicates that it is essential to use reliable estimates of fecundity to limit the risk of under- or overestimating the survival rates when using the KNM method. Survival and fecundity rates for B. calamita populations were then used to define population matrices and make a limited exploration of their growth and viability. The findings of the study recently led to the implementation of practical conservation measures at the sites where populations were most vulnerable to extinction. © 2010 The Society of Population Ecology and Springer.

Raman spectroscopic studies of the cure of dicyclopentadiene (DCPD)

The cure of polydicyclopentadiene conducted by ring-opening metathesis polymerisation in the presence of a Grubbs catalyst was studied using non-invasive Raman spectroscopy. The spectra of the monomer precursor and polymerised product were fully characterised and all stages of polymerisation monitored. Because of the monomer's high reactivity, the cure process is adaptable to reaction injection moulding and reactive rotational moulding. The viscosity of the dicyclopentadiene undergoes a rapid change at the beginning of the polymerisation process and it is critical that the induction time of the viscosity increase is determined and controlled for successful manufacturing. The results from this work show non-invasive Raman spectroscopic monitoring to be an effective method for monitoring the degree of cure, paving the way for possible implementation of the technique as a method of real-time analysis for control and optimisation during reactive processing. Agreement is shown between Raman measurements and ultrasonic time of flight data acquired during the initial induction period of the curing process. (c) 2004 Elsevier B.V. All rights reserved.

The initial mode of action of copper on the cardiac physiology of the blue mussel, Mytilus edulis

Previous studies have shown that low levels of copper (down to 0.8 muM) induce bradycardia in the blue mussel (Mytilus edulis) and that this is not caused by prolonged Valve closure. The aim of this study was to determine the precise mechanism responsible. To establish if copper was directly affecting heart cell physiology, recordings of contractions from isolated ventricular strips were made using an isometric force transducer, in response to copper concentrations (as CuCl2) ranging between 1 muM and 1 mM. Inhibition of mechanical activity only occurred at 1 mM copper, suggesting that the copper-induced bradycardia observed in whole animals cannot be attributed to direct cardiotoxicity. Effects of copper on the cardiac nerves were subsequently examined. Following removal of visceral ganglia (from where the cardiac nerves originate), exposure to 12.5 muM copper had no effect on the heart rate of whole animals. The effect of copper on the heart rate of mussels could not be abolished by depletion of the monoamine content of the animal using reserpine. However, pre-treatment of the animals with alpha -bungarotoxin considerably reduced the sensitivity of the heart to copper. These results indicated that the influence of copper on the heart of M. edulis might be mediated by a change in the activity of cholinergic nerves to heart. In the final experiments, mussels were injected with either benzoquinonium or D-tubocurarine, prior to copper exposure, in an attempt to selectively block the inhibitory or excitatory cholinoreceptors of the heart. Only benzoquinonium decreased the susceptibility of the heart to copper, suggesting that copper affects the cardiac activity of blue mussels by stimulating inhibitory cholinergic nerves to the heart. (C) 2001 Elsevier Science B.V. All rights reserved.