Sensitivity and specificity of detection methods for erythropoietin doping in cyclists

Recombinant human erythropoietin (rHuEPO) is used as doping a substance. Anti-doping efforts include urine and blood testing and monitoring the athlete biological passport (ABP). As data on the performance of these methods are incomplete, this study aimed to evaluate the performance of two common urine assays and the ABP. In a randomized, double-blinded, placebo-controlled trial, 48 trained cyclists received a mean dose of 6000 IU rHuEPO (epoetin beta) or placebo by weekly injection for eight weeks. Seven timed urine and blood samples were collected per subject. Urine samples were analyzed by sarcosyl-PAGE and isoelectric focusing methods in the accredited DoCoLab in Ghent. A selection of samples, including any with false presumptive findings, underwent a second sarcosyl-PAGE confirmation analysis. Hematological parameters were used to construct a module similar to the ABP and analyzed by two evaluators from an Athlete Passport Management Unit. Sensitivity of the sarcosyl-PAGE and isoelectric focusing assays for the detection of erythropoietin abuse were 63.8% and 58.6%, respectively, with a false presumptive finding rate of 4.3% and 6%. None of the false presumptive findings tested positive in the confirmation analysis. Sensitivity was highest between 2 and 6 days after dosing, and dropped rapidly outside this window. Sensitivity of the ABP was 91.3%. Specificity of the urine assays was high; however, the detection window of rHuEPO was narrow, leading to questionable sensitivity. The ABP, integrating longitudinal data, is more sensitive, but there are still subjects that evade detection. Combining these methods might improve performance, but will not resolve all observed shortcomings

Gene expression profiling of dedifferentiated human articular chondrocytes in monolayer culture

Objective\ud When primary chondrocytes are cultured in monolayer, they undergo dedifferentiation during which they lose their phenotype and their capacity to form cartilage. Dedifferentiation is an obstacle for cell therapy for cartilage degeneration. In this study, we aimed to systemically evaluate the changes in gene expression during dedifferentiation of human articular chondrocytes to identify underlying mechanisms.\ud \ud Methods\ud RNA was isolated from monolayer-cultured primary human articular chondrocytes at serial passages. Gene expression was analyzed by microarray. Based on the microarray analysis, relevant genes and pathways were identified. Their functions in chondrocyte dedifferentiation were further investigated.\ud \ud Results\ud In vitro expanded human chondrocytes showed progressive changes in gene expression. Strikingly, an overall decrease in total gene expression was detected, which was both gradual and cumulative. DNA methylation was in part responsible for the expression downregulation of a number of genes. Genes involved in many pathways such as the ERK and BMP pathways exhibited significant changes in expression. Inhibition of ERK pathway didn’t show dramatic effects in counteracting dedifferentiation process. BMP-2 was able to decelerate the dedifferentiation and reinforce the maintenance of chondrocyte phenotype in monolayer culture.\ud \ud Conclusion\ud Our study not only improves our knowledge of the intricate signaling network regulating maintenance of chondrocyte phenotype, but also contributes to improved chondrocyte expansion and chondrogenic performance for cell therapy

A Physics-informed Machine Learning-based Control Method for Nonlinear Dynamic Systems with Highly Noisy Measurements

This study presents a physics-informed machine learning-based control method for nonlinear dynamic systems with highly noisy measurements. Existing data-driven control methods that use machine learning for system identification cannot effectively cope with highly noisy measurements, resulting in unstable control performance. To address this challenge, the present study extends current physics-informed machine learning capabilities for modeling nonlinear dynamics with control and integrates them into a model predictive control framework. To demonstrate the capability of the proposed method we test and validate with two noisy nonlinear dynamic systems: the chaotic Lorenz 3 system, and turning machine tool. Analysis of the results illustrate that the proposed method outperforms state-of-the-art benchmarks as measured by both modeling accuracy and control performance for nonlinear dynamic systems under high-noise conditions

Unrelated Helpers in a Primitively Eusocial Wasp: Is Helping Tailored Towards Direct Fitness?

The paper wasp Polistes dominulus is unique among the social insects in that nearly one-third of co-foundresses are completely unrelated to the dominant individual whose offspring they help to rear and yet reproductive skew is high. These unrelated subordinates stand to gain direct fitness through nest inheritance, raising the question of whether their behaviour is adaptively tailored towards maximizing inheritance prospects. Unusually, in this species, a wealth of theory and empirical data allows us to predict how unrelated subordinates should behave. Based on these predictions, here we compare helping in subordinates that are unrelated or related to the dominant wasp across an extensive range of field-based behavioural contexts. We find no differences in foraging effort, defense behaviour, aggression or inheritance rank between unrelated helpers and their related counterparts. Our study provides no evidence, across a number of behavioural scenarios, that the behaviour of unrelated subordinates is adaptively modified to promote direct fitness interests

ac Josephson effect in the resonant tunneling through mesoscopic superconducting junctions

We investigate ac Josephson effect in the resonant tunneling through mesoscopic superconducting junctions. In the presence of microwave irradiation, we show that the trajectory of multiple Andreev reflections can be closed by emitting or absorbing photons. Consequently, photon-assisted Andreev states are formed and play the role of carrying supercurrent. On the Shapiro steps, dc component appears when the resonant level is near a series of positions with spacing of half of the microwave frequency. Analytical result is derived in the limit of infinite superconducting gap, based on which new features of ac Josephson effect are revealed.Comment: 11 pages, 3 figure

Vertical zonation of testate amoebae in the Elatia Mires, northern Greece : palaeoecological evidence for a wetland response to recent climate change or autogenic processes?

The Elatia Mires of northern Greece are unique ecosystems of high conservation value. The mires are climatically marginal and may be sensitive to changing hydroclimate, while northern Greece has experienced a significant increase in aridity since the late twentieth century. To investigate the impact of recent climatic change on the hydrology of the mires, the palaeoecological record was investigated from three near-surface monoliths extracted from two sites. Testate amoebae were analysed as sensitive indicators of hydrology. Results were interpreted using transfer function models to provide quantitative reconstructions of changing water table depth and pH. AMS radiocarbon dates and 210Pb suggest the peats were deposited within the last c. 50 years, but do not allow a secure chronology to be established. Results from all three profiles show a distinct shift towards a more xerophilic community particularly noted by increases in Euglypha species. Transfer function results infer a distinct lowering of water tables in this period. A hydrological response to recent climate change is a tenable hypothesis to explain this change; however other possible explanations include selective test decay, vertical zonation of living amoebae, ombrotrophication and local hydrological change. It is suggested that a peatland response to climatic change is the most probable hypothesis, showing the sensitivity of marginal peatlands to recent climatic change

Real-time cancellation of temperature induced resonance shifts in SOI wire waveguide ring resonator label-free biosensor arrays.

A comprehensive investigation of real-time temperature-induced resonance shift cancellation for silicon wire based biosensor arrays is reported for the first time. A reference resonator, protected by either a SU8 or SiO(2) cladding layer, is used to track temperature changes. The temperature dependence of resonators in aqueous solutions, pertinent to biosensing applications, is measured under steady-state conditions and the operating parameters influencing these properties are discussed. Real-time measurements show that the reference resonator resonances reflect the temperature changes without noticeable time delay, enabling effective cancellation of temperature-induced shifts. Binding between complementary IgG protein pairs is monitored over 4 orders of magnitude dynamic range down to a concentration of 20 pM, demonstrating a resolvable mass of 40 attograms. Reactions are measured over time periods as long as 3 hours with high stability, showing a scatter corresponding to a fluid refractive index fluctuation of ± 4 × 10(-6) in the baseline data. Sensor arrays with a SU8 protective cladding are easy to fabricate, while oxide cladding is found to provide superior stability for measurements involving long time scales

Comparison of parameter sensitivities between a laboratory and field scale model of uranium transport in a dual domain, distributed rate reactive system

A laboratory-derived conceptual and numerical model for U(VI) transport at the Hanford 300A site, Washington, USA, was applied to a range of field-scale scenarios of different geochemical complexity to identify the importance of individual processes in controlling the fate of U(VI), as well as to elucidate the characteristic differences between well-defined laboratory and the more complex field-scale conditions. Therefore, a rigorous sensitivity analysis was carried out for the various simulation scenarios. The underlying conceptual and numerical model, originally developed from column experiment data, includes distributed rate surface complexation kinetics of U(VI), aqueous speciation, and physical nonequilibrium transport processes. The field scenarios accounted additionally for highly transient groundwater flow and variable geochemical conditions driven by frequent water level changes of the nearby Columbia River. The results of the sensitivity analysis showed not only similarities but also important differences in parameter sensitivities between the laboratory and field-scale models. It was found that the actual degree of sorption disequilibrium, actual concentration of sorbed U(VI), and the sorption extent (i.e., theoretical concentration of sorbed U(VI) at equilibrium) are the major controls for the magnitude of the calculated parameter sensitivities. These internal model variables depended mainly on (1) the groundwater flow conditions, i.e., the relatively long phases of limited groundwater movement in the field scale (intercepted by short peak flow events) and the long sustained flow phases in the column experiment (intercepted by relatively short stop flow events), and (2) the sampling location in the field-scale model, i.e., plume fringe versus plume center. Copyright 2010 by the American Geophysical Union

What are we measuring? A critique of range of motion methods currently in use for Dupuytren's disease and recommendations for practice

Background: Range of motion is the most frequently reported measure used in practice to evaluate outcomes. A goniometer is the most reliable tool to assess range of motion yet, the lack of consistency in reporting prevents comparison between studies. The aim of this study is to identify how range of motion is currently assessed and reported in Dupuytren’s disease literature. Following analysis recommendations for practice will be made to enable consistency in future studies for comparability. This paper highlights the variation in range of motion reporting in Dupuytren’s disease. Methods: A Participants, Intervention, Comparison, Outcomes and Study design format was used for the search strategy and search terms. Surgery, needle fasciotomy or collagenase injection for primary or recurrent Dupuytren’s disease in adults were included if outcomes were monitored using range of motion to record change. A literature search was performed in May 2013 using subject heading and free-text terms to also capture electronic publications ahead of print. In total 638 publications were identified and following screening 90 articles met the inclusion criteria. Data was extracted and entered onto a spreadsheet for analysis. A thematic analysis was carried out to establish any duplication, resulting in the final range of motion measures identified. Results: Range of motion measurement lacked clarity, with goniometry reportedly used in only 43 of the 90 studies, 16 stated the use of a range of motion protocol. A total of 24 different descriptors were identified describing range of motion in the 90 studies. While some studies reported active range of motion, others reported passive or were unclear. Eight of the 24 categories were identified through thematic analysis as possibly describing the same measure, ‘lack of joint extension’ and accounted for the most frequently used. Conclusions: Published studies lacked clarity in reporting range of motion, preventing data comparison and meta-analysis. Percentage change lacks context and without access to raw data, does not allow direct comparison of baseline characteristics. A clear description of what is being measured within each study was required. It is recommended that range of motion measuring and reporting for Dupuytren’s disease requires consistency to address issues that fall into 3 main categories:- Definition of terms Protocol statement Outcome reportin

Food-web structure in relation to environmental gradients and predator-prey ratios in tank-bromeliad ecosystems

Little is known of how linkage patterns between species change along environmental gradients. The small, spatially discrete food webs inhabiting tank-bromeliads provide an excellent opportunity to analyse patterns of community diversity and food-web topology (connectance, linkage density, nestedness) in relation to key environmental variables (habitat size, detrital resource, incident radiation) and predators: prey ratios. We sampled 365 bromeliads in a wide range of understorey environments in French Guiana and used gut contents of invertebrates to draw the corresponding 365 connectance webs. At the bromeliad scale, habitat size (water volume) determined the number of species that constitute food-web nodes, the proportion of predators, and food-web topology. The number of species as well as the proportion of predators within bromeliads declined from open to forested habitats, where the volume of water collected by bromeliads was generally lower because of rainfall interception by the canopy. A core group of microorganisms and generalist detritivores remained relatively constant across environments. This suggests that (i) a highly-connected core ensures food-web stability and key ecosystem functions across environments, and (ii) larger deviations in food-web structures can be expected following disturbance if detritivores share traits that determine responses to environmental changes. While linkage density and nestedness were lower in bromeliads in the forest than in open areas, experiments are needed to confirm a trend for lower food-web stability in the understorey of primary forests