An atomic force microscope operating at hypergravity for in situ measurement of cellular mechano-response

We present a novel atomic force microscope (AFM) system, operational in liquid at variable gravity, dedicated to image cell shape changes of cells in vitro under hypergravity conditions. The hypergravity AFM is realized by mounting a stand-alone AFM into a large-diameter centrifuge. The balance between mechanical forces, both intra- and extracellular, determines both cell shape and integrity. Gravity seems to be an insignificant force at the level of a single cell, in contrast to the effect of gravity on a complete (multicellular) organism, where for instance bones and muscles are highly unloaded under near weightless (microgravity) conditions. However, past space flights and ground based cell biological studies, under both hypogravity and hypergravity conditions have shown changes in cell behaviour (signal transduction), cell architecture (cytoskeleton) and proliferation. Thus the role of direct or indirect gravity effects at the level of cells has remained unclear. Here we aim to address the role of gravity on cell shape. We concentrate on the validation of the novel AFM for use under hypergravity conditions. We find indications that a single cell exposed to 2 to 3 × g reduces some 30–50% in average height, as monitored with AFM. Indeed, in situ measurements of the effects of changing gravitational load on cell shape are well feasible by means of AFM in liquid. The combination provides a promising technique to measure, online, the temporal characteristics of the cellular mechano-response during exposure to inertial forces

Lifetime vigorous but not light-to-moderate habitual physical activity impacts favorably on carotid stiffness in young adults the Amsterdam growth and health longitudinal study

Higher levels of habitual physical activity favorably impact on arterial stiffness. It is not clear, however, whether lifetime habitual physical activities of different intensities carry the same protective effect and to what extent any such effect is mediated by other biological cardiovascular risk factors. We, therefore, examined longitudinal data on habitual physical activity and cardiovascular risk factors (8 repeated measures between the ages of 13 and 36 years) in 373 subjects in whom stiffness estimates of the carotid artery were assessed at age 36 years using noninvasive ultrasonography. The time spent in habitual physical activities (in minutes per week) throughout the longitudinal period was compared between subjects across tertiles of the following stiffness estimates: β-stiffness index, distensibility and compliance coefficients, and the Young's elastic modulus. After adjustments for sex, body height, and other lifestyle variables, subjects in the highest tertile of the β-stiffness index (ie, with stiffer arteries) had spent, on average, throughout the longitudinal period, less time in vigorous (-26.5 [95% CI:-45.9 to-7.1]) but less so in light-to-moderate habitual physical activities (-11.2 [95% CI:-53.5 to 31.1]) as compared with subjects in the lowest tertile. The difference in time spent in vigorous activities was greatly attenuated when further adjusted for blood lipids, cardiorespiratory fitness, fat distribution, resting heart rate, and mean arterial pressure (to-11.2 [95% CI:-29.4 to 7.0]). Similar results were found for the other stiffness estimates. Promoting vigorous intensity physical activities among the healthy young may, therefore, prevent arterial stiffness and related cardiovascular sequelae later in life, partly through its favorable impact on other biological cardiovascular risk factors

Visualization of vessel traffic

We discuss methods to visualize large amounts of object movements described with so called multivariate trajectories, which are lists of records with multiple attribute values about the state of the object. In this chapter we focus on vessel traffic as one of the examples of this kind of data. The purpose of our visualizations is to reveal what has happened over a period of time. For vessel traffic, this is beneficial for surveillance operators and analysts, since current visualizations do not give an overview of normal behavior, which is needed to find abnormally behaving ships that can be a potential threat. Our approach is inspired by the technique of kernel density estimation and smooths trajectories to obtain an overview picture with a distribution of trajectories: a density map. Using knowledge about the attributes in the data, the user can adapt these pictures by setting parameters, filters, and expressions as means for rapid prototyping, required for quickly finding other types of behavior with our visualization approach. Furthermore, density maps are computationally expensive, which we address by implementing our tools on graphics hardware. We describe different variations of our techniques and illustrate them with real-world vessel traffic data

Protocol of a randomised delayed-start double-blind placebo-controlled multi-centre trial for Levodopa in EArly Parkinson's disease: the LEAP-study

Contains fulltext : 152630.pdf (publisher's version ) (Open Access)BACKGROUND: The aim of this study is to investigate if early treatment with levodopa has a beneficial disease modifying effect on Parkinson's disease (PD) symptoms and functional health, improves the ability to (maintain) work, and reduces the use of (informal) care, caregiver burden, and costs. Additionally, cost-effectiveness and cost-utility of early levodopa treatment will be assessed. METHODS: To differentiate between the direct symptomatic effects and possible disease modifying effects of levodopa, we use a randomised delayed-start double-blind placebo-controlled multi-centre trial design. Patients with early stage PD whose functional health does not yet necessitate initiation of PD-medication will be randomised to either 40 weeks of treatment with levodopa/carbidopa 100/25 mg TID including 2 weeks of dose escalation or to 40 weeks placebo TID. Subsequently, all patients receive levodopa/carbidopa 100/25 mg TID for 40 weeks. There are 8 assessments: at baseline and at 4, 22, 40, 44, 56, 68, and 80 weeks. The primary outcome measure is the difference in the mean total Unified Parkinson's Disease Rating Scale scores between the early- and delayed-start groups at 80 weeks. Secondary outcome measures are rate of progression, the AMC Linear Disability Score, side effects, perceived quality of life with the Parkinson's Disease Questionnaire-39, the European Quality of Life-5 Dimensions (EQ-5D), ability to (maintain) work, the use of (informal) care, caregiver burden, and costs. 446 newly diagnosed PD patients without impaired functional health need to be recruited in order to detect a minimal clinical relevant difference of 4 points on the total UPDRS at 80 weeks. DISCUSSION: The LEAP-study will provide insights into the possible disease modifying effects of early levodopa. TRIAL REGISTRATION: ISRCTN30518857 , EudraCT number 2011-000678-72

Long-term superiority of subthalamic nucleus stimulation over pallidotomy in Parkinson disease.

Contains fulltext : 79944.pdf (publisher's version ) (Closed access