Technical performance and diagnostic utility of the new Elecsys (R) neuron-specific enolase enzyme immunoassay

This international multicenter study was designed to evaluate the technical performance of the new double-monoclonal, single-step Elecsys neuron-specific enolase (NSE) enzyme immunoassay (EIA) and to assess its utility as a sensitive and specific test for the diagnosis of small-cell lung cancer (SCLC). Intra and interassay coefficients of variation, determined in five control or serum specimens in six laboratories, ranged from 0.7 to 5.3 (interlaboratory median: 1.3%) and from 1.3 to 8.5 (interlaboratory median: 3.4%), respectively. Laboratory-to-laboratory comparability was excellent with respect to recovery and interassay coefficients of variation. The test was linear between 0.0 and 320 ng/ml (highest measured concentration). There was a significant correlation between NSE concentrations measured using the Elecsys NSE and the established Cobas Core NSE EIA II in all subjects (n=723) and in patients with lung cancer (n=333). However, NSE concentrations were systematically lower (approximately 9%) with the Elecsys NSE than with the comparison test. Based on a specificity of 95% in comparison with the group suffering from benign lung diseases (n=183), the cutoff value for the discrimination between malignant and benign conditions was set at 21.6 ng/ml. NSE was raised in 73.4% of SCLC patients (n=188) and was significantly higher (p<0.01) in extensive (87.8%) as opposed to limited disease (56.7%). NSE was also elevated in 16.0% of the cases with non-small cell lung cancer (NSCLC, n=374). It is concluded that the Elecsys NSE EIA is a reliable and accurate diagnostic procedure for the measurement of NSE in serum samples. The special merits of this new assay are the wide measuring range (according to manufacturers declaration up to 370 ng/ml) and a short incubation time of 18 min

Chronic Obstructive Pulmonary Disease: Effects beyond the Lungs

Peter Barnes discusses the growing epidemic of chronic obstructive pulmonary disease (COPD), especially in developing countries and among nonsmokers

AhR transcriptional activity in serum of Inuits across Greenlandic districts

<p>Abstract</p> <p>Background</p> <p>Human exposure to lipophilic persistent organic pollutants (POPs) including polychlorinated dibenzo-<it>p</it>-dioxins/furans (PCDDs/PCDFs), polychlorinated biphenyls (PCBs) and organochlorine pesticide is ubiquitous. The individual is exposed to a complex mixture of POPs being life-long beginning during critical developmental windows. Exposure to POPs elicits a number of species- and tissue-specific toxic responses, many of which involve the aryl hydrocarbon receptor (AhR). The aim of this study was to compare the actual level of integrated AhR transcriptional activity in the lipophilic serum fraction containing the actual POP mixture among Inuits from different districts in Greenland, and to evaluate whether the AhR transactivity is correlated to the bio-accumulated POPs and/or lifestyle factors.</p> <p>Methods</p> <p>The study included 357 serum samples from the Greenlandic districts: Nuuk and Sisimiut (South West Coast), Qaanaaq (North Coast) and Tasiilaq (East Coast). The bio-accumulated serum POPs were extracted by ethanol: hexane and clean-up on Florisil columns. Effects of the serum extract on the AhR transactivity was determined using the Hepa 1.12cR mouse hepatoma cell line carrying an AhR-luciferase reporter gene, and the data was evaluated for possible association to the serum levels of 14 PCB congeners, 10 organochlorine pesticide residues and/or lifestyle factors.</p> <p>Results</p> <p>In total 85% of the Inuit samples elicited agonistic AhR transactivity in a district dependent pattern. The median level of the AhR-TCDD equivalent (AhR-TEQ) of the separate genders was similar in the different districts. For the combined data the order of the median AhR-TEQ was Tasiilaq > Nuuk ≥ Sisimiut > Qaanaaq possibly being related to the different composition of POPs. In overall, the AhR transactivity was inversely correlated to the levels of sum POPs, age and/or intake of marine food.</p> <p>Conclusion</p> <p>i) We observed that the proportion of dioxin like (DL) compounds in the POP mixture was the dominating factor affecting the level of serum AhR transcriptional activity even at very high level of non DL-PCBs; ii) The inverse association between the integrated serum AhR transactivity and sum of POPs might be explained by the higher level of compounds antagonizing the AhR function probably due to selective POP bioaccumulation in the food chain.</p

The Psychiatric Case Register Middle Netherlands

<p>Abstract</p> <p>Background</p> <p>The Psychiatric Case Register Middle Netherlands (PCR-MN) registers the mental healthcare consumption of over Dutch 760,000 inhabitants in the centre of the Netherlands. In 2010 the follow-up period was over ten years. In this paper we describe the content, aims and research potential of this case register.</p> <p>Description</p> <p>All mental healthcare institutions in the middle-western part of the province of Utrecht participate in the PCR-MN case register. All in- and out-patients treated in these institutions have been included in the database from the period 2000 to 2010. Diagnosis according to DSM-IV on axis I to IV, visits to in- and out-patient clinics and basic demographics are recorded. A major advantage of this register is the possibility to link patients anonymously from the PCR-MN cohort to other databases to analyze relationships with determinants and outcomes, such as somatic healthcare consumption, mortality, and demographics, which further increases the research potential</p> <p>Conclusions</p> <p>The PCR-MN database has a large potential for scientific research because of its size, duration of follow-up and ability to link with additional databases, and is accessible for academic researchers.</p

Augmented visual feedback of movement performance to enhance walking recovery after stroke : study protocol for a pilot randomised controlled trial

Increasing evidence suggests that use of augmented visual feedback could be a useful approach to stroke rehabilitation. In current clinical practice, visual feedback of movement performance is often limited to the use of mirrors or video. However, neither approach is optimal since cognitive and self-image issues can distract or distress patients and their movement can be obscured by clothing or limited viewpoints. Three-dimensional motion capture has the potential to provide accurate kinematic data required for objective assessment and feedback in the clinical environment. However, such data are currently presented in numerical or graphical format, which is often impractical in a clinical setting. Our hypothesis is that presenting this kinematic data using bespoke visualisation software, which is tailored for gait rehabilitation after stroke, will provide a means whereby feedback of movement performance can be communicated in a more meaningful way to patients. This will result in increased patient understanding of their rehabilitation and will enable progress to be tracked in a more accessible way. The hypothesis will be assessed using an exploratory (phase II) randomised controlled trial. Stroke survivors eligible for this trial will be in the subacute stage of stroke and have impaired walking ability (Functional Ambulation Classification of 1 or more). Participants (n = 45) will be randomised into three groups to compare the use of the visualisation software during overground physical therapy gait training against an intensity-matched and attention-matched placebo group and a usual care control group. The primary outcome measure will be walking speed. Secondary measures will be Functional Ambulation Category, Timed Up and Go, Rivermead Visual Gait Assessment, Stroke Impact Scale-16 and spatiotemporal parameters associated with walking. Additional qualitative measures will be used to assess the participant's experience of the visual feedback provided in the study. Results from the trial will explore whether the early provision of visual feedback of biomechanical movement performance during gait rehabilitation demonstrates improved mobility outcomes after stroke and increased patient understanding of their rehabilitation

PKA-regulated VASP phosphorylation promotes extrusion of transformed cells from the epithelium.

At the early stages of carcinogenesis, transformation occurs in single cells within tissues. In an epithelial monolayer, such mutated cells are recognized by their normal neighbors and are often apically extruded. The apical extrusion requires cytoskeletal reorganization and changes in cell shape, but the molecular switches involved in the regulation of these processes are poorly understood. Here, using stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative mass spectrometry, we have identified proteins that are modulated in transformed cells upon their interaction with normal cells. Phosphorylation of VASP at serine 239 is specifically upregulated in Ras(V12)-transformed cells when they are surrounded by normal cells. VASP phosphorylation is required for the cell shape changes and apical extrusion of Ras-transformed cells. Furthermore, PKA is activated in Ras-transformed cells that are surrounded by normal cells, leading to VASP phosphorylation. These results indicate that the PKA-VASP pathway is a crucial regulator of tumor cell extrusion from the epithelium, and they shed light on the events occurring at the early stage of carcinogenesis

Comparison of embedded and added motor imagery training in patients after stroke: Study protocol of a randomised controlled pilot trial using a mixed methods approach

Copyright @ 2009 Schuster et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Two different approaches have been adopted when applying motor imagery (MI) to stroke patients. MI can be conducted either added to conventional physiotherapy or integrated within therapy sessions. The proposed study aims to compare the efficacy of embedded MI to an added MI intervention. Evidence from pilot studies reported in the literature suggests that both approaches can improve performance of a complex motor skill involving whole body movements, however, it remains to be demonstrated, which is the more effective one.Methods/Design: A single blinded, randomised controlled trial (RCT) with a pre-post intervention design will be carried out. The study design includes two experimental groups and a control group (CG). Both experimental groups (EG1, EG2) will receive physical practice of a clinical relevant motor task ('Going down, laying on the floor, and getting up again') over a two week intervention period: EG1 with embedded MI training, EG2 with MI training added after physiotherapy. The CG will receive standard physiotherapy intervention and an additional control intervention not related to MI.The primary study outcome is the time difference to perform the task from pre to post-intervention. Secondary outcomes include level of help needed, stages of motor task completion, degree of motor impairment, balance ability, fear of falling measure, motivation score, and motor imagery ability score. Four data collection points are proposed: twice during baseline phase, once following the intervention period, and once after a two week follow up. A nested qualitative part should add an important insight into patients' experience and attitudes towards MI. Semi-structured interviews of six to ten patients, who participate in the RCT, will be conducted to investigate patients' previous experience with MI and their expectations towards the MI intervention in the study. Patients will be interviewed prior and after the intervention period.Discussion: Results will determine whether embedded MI is superior to added MI. Findings of the semi-structured interviews will help to integrate patient's expectations of MI interventions in the design of research studies to improve practical applicability using MI as an adjunct therapy technique

Preventing Establishment: An Inventory of Introduced Plants in Puerto Villamil, Isabela Island, Galapagos

As part of an island-wide project to identify and eradicate potentially invasive plant species before they become established, a program of inventories is being carried out in the urban and agricultural zones of the four inhabited islands in Galapagos. This study reports the results of the inventory from Puerto Villamil, a coastal village representing the urban zone of Isabela Island. We visited all 1193 village properties to record the presence of the introduced plants. In addition, information was collected from half of the properties to determine evidence for potential invasiveness of the plant species. We recorded 261 vascular taxa, 13 of which were new records for Galapagos. Most of the species were intentionally grown (cultivated) (73.3%) and used principally as ornamentals. The most frequent taxa we encountered were Cocos nucifera (coconut tree) (22.1%) as a cultivated plant and Paspalum vaginatum (salt water couch) (13.2%) as a non cultivated plant. In addition 39 taxa were naturalized. On the basis of the invasiveness study, we recommend five species for eradication (Abutilon dianthum, Datura inoxia, Datura metel, Senna alata and Solanum capsicoides), one species for hybridization studies (Opuntia ficus-indica) and three species for control (Furcraea hexapetala, Leucaena leucocephala and Paspalum vaginatum)

Explicating ways of consensus-making in science and society: distinguishing the academic, the interface and the meta-consensus

In this chapter, we shed new light on the epistemic struggle between establishing consensus and acknowledging plurality, by explicating different ways of consensus-making in science and society and examining the impact hereof on their field of intersection, i.e. consensus conferences (in particular those organized by the National Institute of Health). We draw a distinction between, what we call, academic and interface consensus, to capture the wide appeal to consensus in existing literature. We investigate such accounts - i.e. from Miriam Solomon, John Beatty and Alfred Moore, and Boaz Miller - as to put forth a new understanding of consensus-making, focusing on the meta-consensus. We further defend how (NIH) consensus conferences enable epistemic work, through demands of epistemic adequacy and contestability, contrary to the claim that consensus conferences miss a window for epistemic opportunity (Solomon M, The social epistemology of NIH consensus conferences. In: Kincaid H, McKitrick J (ed) Establishing medical reality: methodological and metaphysical issues in philosophy of medicine. Springer, Dordrecht, 2007). Paying attention to the dynamics surrounding consensus, moreover, allows us to illustrate how the public understanding of science and the public use of the ideal of consensus could be well modified

On the Origin of S0 Galaxies

I will review the basic properties of S0 galaxies in the local Universe in relation to both elliptical and spiral galaxies, their neighbours on the Hubble sequence, and also in relation to dwarf spheroidal (dSph) galaxies. This will include colours, luminosities, spectral features, information about the age and metallicity composition of their stellar populations and globular clusters, about their ISM content, as well as kinematic signatures and their implications for central black hole masses and past interaction events, and the number ratios of S0s to other galaxy types in relation to environmental galaxy density. I will point out some caveats as to their morphological discrimination against other classes of galaxies, discuss the role of dust and the wavelength dependence of bulge/disk light ratios. These effects are of importance for investigations into the redshift evolution of S0 galaxies -- both as individual objects and as a population. The various formation and transformation scenarios for S0 and dSph galaxies will be presented and confronted with the available observations.Comment: Invited Review, 18 pages, ``BARS 2004'' Conference, South Africa, June 2004, eds.: K. C. Freeman, D. L. Block, I. Puerari, R. Groess, Kluwer, in pres