Adaptive Brain Stimulation for Movement Disorders

Deep brain stimulation (DBS) has markedly changed how we treat movement disorders including Parkinson's disease (PD), dystonia, and essential tremor (ET). However, despite its demonstrable clinical benefit, DBS is often limited by side effects and partial efficacy. These limitations may be due in part to the fact that DBS interferes with both pathological and physiological neural activities. DBS could, therefore, be potentially improved were it applied selectively and only at times of enhanced pathological activity. This form of stimulation is known as closed-loop or adaptive DBS (aDBS). An aDBS approach has been shown to be superior to conventional DBS in PD in primates using cortical neuronal spike triggering and in humans employing local field potential biomarkers. Likewise, aDBS studies for essential and Parkinsonian tremor are advancing and show great promise, using both peripheral or central sensing and stimulation. aDBS has not yet been trialed in dystonia and yet exciting and promising biomarkers suggest it could be beneficial here too. In this chapter, we will review the existing literature on aDBS in movement disorders and explore potential biomarkers and stimulation algorithms for applying aDBS in PD, ET, and dystonia

Quantum Force in Superconductor

Transitions between states with continuous (called as classical state) and discrete (called as quantum state) spectrum of permitted momentum values is considered. The persistent current can exist along the ring circumference in the quantum state in contrast to the classical state. Therefore the average momentum can changes at the considered transitions. In order to describe the reiterated switching into and out the quantum state an additional term is introduced in the classical Boltzmann transport equation. The force inducing the momentum change at the appearance of the persistent current is called as quantum force. It is shown that dc potential difference is induced on ring segments by the reiterated switching if the dissipation force is not homogeneous along the ring circumference. The closing of the superconducting state in the ring is considered as real example of the transition from classical to quantum stateComment: 4 pages, RevTex, 0 figure

Advanced turboprop testbed systems study. Volume 1: Testbed program objectives and priorities, drive system and aircraft design studies, evaluation and recommendations and wind tunnel test plans

The establishment of propfan technology readiness was determined and candidate drive systems for propfan application were identified. Candidate testbed aircraft were investigated for testbed aircraft suitability and four aircraft selected as possible propfan testbed vehicles. An evaluation of the four candidates was performed and the Boeing KC-135A and the Gulfstream American Gulfstream II recommended as the most suitable aircraft for test application. Conceptual designs of the two recommended aircraft were performed and cost and schedule data for the entire testbed program were generated. The program total cost was estimated and a wind tunnel program cost and schedule is generated in support of the testbed program

7-Li(p,n) Nuclear Data Library for Incident Proton Energies to 150 MeV

We describe evaluation methods that make use of experimental data, and nuclear model calculations, to develop an ENDF-formatted data library for the reaction p + Li7 for incident protons with energies up to 150 MeV. The important 7-Li(p,n_0) and 7-Li(p,n_1) reactions are evaluated from the experimental data, with their angular distributions represented using Lengendre polynomial expansions. The decay of the remaining reaction flux is estimated from GNASH nuclear model calculations. The evaluated ENDF-data are described in detail, and illustrated in numerous figures. We also illustrate the use of these data in a representative application by a radiation transport simulation with the code MCNPX.Comment: 11 pages, 8 figures, LaTeX, submitted to Proc. 2000 ANS/ENS International Meeting, Nuclear Applications of Accelerator Technology (AccApp00), November 12-16, Washington, DC, US

Calcific aortic valve disease and hypertension

This review addresses the role of hypertension in precipitating Calcific aortic valve disease (CAVD) and the therapeutic potential of anti-hypertensive interventions to ameliorate CAVD. CAVD was originally considered to be a degenerative disease representing the "wear and tear" of the aortic valves. More recently both conceptually and experimentally, CAVD has come to be considered the result of an active disease process, Whilst, there are some common factors in the pathology and risk factors for atherosclerosis and CAVD there are also some distinct differences. Hypertension is an established risk factor for coronary artery disease and has been recognised as a risk factor for CAVD. Angiotensin converting enzyme inhibitors have been found to have beneficial effects in CAVD and as in atherosclerosis such effects may be due to the blood pressure lowering action but also to direct pleiotropic effects on the biochemical and cellular mechanisms of disease progression in the respective tissues. The very high prevalence of hypertension in the community coupled with an aging population, a risk factor associated with both hypertension and CAVD, infers that hypertension will be one of the predominant factors that increase the impact of CAVD on human health in the coming decades

p38 MAP kinase mediated proteoglycan synthesis as a target for the prevention of atherosclerosis

The major underlying pathology of most cardiovascular disease is the chronic inflammatory disease of atherosclerosis. Type 2 diabetes, also recognised as an inflammatory condition, accelerates the development of atherosclerosis. Current therapies for atherosclerosis target risk factors such as elevated blood lipids and hypertension and are of strong but limited efficacy. The "response to retention" hypothesis states that atherosclerosis is initiated by the accumulation of lipids through binding to extracellular matrix, and this is specifically the glycosaminoglycan (GAG) chains on proteoglycans. Many vasoactive agonists stimulate changes in the structure of the GAGs which increase lipid binding and the relevant signalling pathways are a potential therapeutic target. It has recently been demonstrated that the actions of transforming growth factor b; on vascular smooth muscle proteoglycan synthesis involves signalling through p38 MAP kinase and inhibition of this pathway reduces binding of lipids. Inhibition of p38 MAP kinase will elicit a wide spread antiinflammatory response which may alleviate some of the deleterious processes in cardiovascular tissues. This article explores the potential for the actions of p38 MAP kinase inhibitors directed at proteoglycan synthesis in vascular smooth muscle to contribute to the beneficial outcomes from targeting p38 MAP kinase for the prevention of cardiovascular disease

Relationship between environmental exposure to pesticides and anthropometric outcomes of boys in the rural Western Cape, South Africa

BACKGROUND: Rural residents in the Western Cape (WC), South Africa (SA) are highly exposed to agricultural pesticides that could impact their reproductive development. However, epidemiological evidence of the effect of pesticides on pubertal growth is contradictory. OBJECTIVE: To investigate the effect of pesticide exposure measured using indices of environmental exposure to pesticides on the pubertal growth of boys in rural WC, SA. METHODS: A cross-sectional study of 269 boys (177 of whom gave a history of residing on farms) was conducted. A questionnaire was administered, height and weight were measured and body mass index was calculated. A proximity index (PI) and spraying index (SI) was developed, measuring the lifetime average home distance from pesticide spraying and average frequency of spraying pesticides on a farm, respectively. RESULTS: Median age of boys was 12.4 years (interquartile range 9.5 - 13.3). More than 60% boys had height and weight <50th percentile for age. After adjusting for confounders, PI was significantly associated with shorter stature and lower weight (-1.7 cm/10-fold decrease, p=0.02 and -1.24 kg/10-fold decrease, p=0.04; respectively) and SI was non-significantly associated (-1.4 cm/10-fold increase, p=0.05 and -1.1 cm/10-fold increase, p=0.06; respectively). Associations were stronger for boys aged <11 years and were weaker when excluding non- farm boys. There were no other associations between outcome and exposure. CONCLUSIONS: The use of quantitative exposure indices showed that lower heights and weights might be associated with pesticide exposure in farm boys v. non-farm boys, but not among farm boys. Lower anthropometric measurements among farm boys v. non-farm boys appear stronger at a younger age. The indices of environmental exposure to pesticides require further development