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

Proteolytic degradation and potential role of onconeural protein cdr2 in neurodegeneration

Cerebellar degeneration-related protein 2 (cdr2) is expressed in the central nervous system, and its ectopic expression in tumor cells of patients with gynecological malignancies elicits immune responses by cdr2-specific autoantibodies and T lymphocytes, leading to neurological symptoms. However, little is known about the regulation and function of cdr2 in neurodegenerative diseases. Because we found that cdr2 is highly expressed in the midbrain, we investigated the role of cdr2 in experimental models of Parkinson's disease (PD). We found that cdr2 levels were significantly reduced after stereotaxic injection of 1-methyl-4-phenylpyridinium (MPP+) into the striatum. cdr2 levels were also decreased in the brains of post-mortem PD patients. Using primary cultures of mesencephalic neurons and MN9D cells, we confirmed that MPP + reduces cdr2 in tyrosine hydroxylase-positive dopaminergic neuronal cells. The MPP+-induced decrease of cdr2 was primarily caused by calpain-and ubiquitin proteasome system-mediated degradation, and cotreatment with pharmacological inhibitors of these enzymes or overexpression of calcium-binding protein rendered cells less vulnerable to MPP+-mediated cytotoxicity. Consequently, overexpression of cdr2 rescued cells from MPP+-induced cytotoxicity, whereas knockdown of cdr2 accelerated toxicity. Collectively, our findings provide insights into the novel regulatory mechanism and potentially protective role of onconeural protein during dopaminergic neurodegeneration. © 2016 Macmillan Publishers Limited All rights reserved.1

Constraints on the geometry of the subducted Gorda Plate from converted phases generated by local earthquakes

Author Posting. © American Geophysical Union, 2021. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Solid Earth 126(2), (2021): e2020JB019962, https://doi.org/10.1029/2020JB019962.The largest slip in great megathrust earthquakes often occurs in the 10–30 km depth range, yet seismic imaging of the material properties in this region has proven difficult. We utilize a dense onshore‐offshore passive seismic dataset from the southernmost Cascadia subduction zone where seismicity in the mantle of the subducted Gorda Plate produces S‐to‐P and P‐to‐S conversions generated within a few km of the plate interface. These conversions typically occur in the 10–20 km depth range at either the top or bottom of a ∼5 km thick layer with a high Vp/Vs that we infer to be primarily the subducted crust. We use their arrival times and amplitudes to infer the location of the top and bottom of the subducted crust as well as the velocity contrasts across these discontinuities. Comparing with both the Slab1.0 and the updated Slab2 interface models, the Slab2 model is generally consistent with the converted phases, while the Slab1.0 model is 1–2 km deeper in the 2–20 km depth range and ∼6–8 km too deep in the 10–20 km depth range between 40.25°N and 40.4°N. Comparing the amplitudes of the converted phases to synthetics for simplified velocity structures, the amplitude of the converted phases requires models containing a ∼5 km thick zone with at least a ∼10%–20% reduction in S wave velocity. Thus, the plate boundary is likely contained within or at the top of this low velocity zone, which potentially indicates a significant porosity and fluid content within the seismogenic zone.This work is funded by National Science Foundation Award Numbers EAR‐1520690.2021-07-2

Squeezed States of the Generalized Minimum Uncertainty State for the Caldirola-Kanai Hamiltonian

We show that the ground state of the well-known pseudo-stationary states for the Caldirola-Kanai Hamiltonian is a generalized minimum uncertainty state, which has the minimum allowed uncertainty $\Delta q \Delta p = \hbar \sigma_0/2$, where $\sigma_0 (\geq 1)$ is a constant depending on the damping factor and natural frequency. The most general symmetric Gaussian states are obtained as the one-parameter squeezed states of the pseudo-stationary ground state. It is further shown that the coherent states of the pseudo-stationary ground state constitute another class of the generalized minimum uncertainty states.Comment: RevTex4, 9 pages, no fingure; to be published in Journal of Physics

An assessment of the relationships between extreme weather events, vulnerability, and the impacts on human wellbeing in Latin America

Climate change and variability are known to have an influence on human wellbeing in a variety of ways. In Latin America, such forces are especially conspicuous, particularly in respect of extreme climatological, hydrological, and weather events (EWEs) and climate-sensitive disasters (CSDs). Consistent with the need to study further such connections, this paper presents an analysis of some of the vulnerabilities of environmental health issues and climate-related impacts that are focusing on EWEs and CSDs in Latin American countries. The research includes an analysis of the (i) human and socio-economic development; (ii) geographical and socio-economic determinants of vulnerability and adaptability of environmental health issues (exposure, sensitivity, and adaptive capacity); (iii) occurrence of CSDs from 1988 to 2017 and their direct impacts on human wellbeing (Total death and Affected people); (iv) an online survey on the perceptions of the effects of EWEs on human wellbeing in a sample of countries in the region; and (v) discussion of possible solutions. The socio-economic and development indices, and the International Disaster Database (EM-DAT) and Climate-Risk Index (CRI) disaster statistics suggest that the impacts of CSDs are primarily related to socio-economic determinants of human wellbeing and health inequalities. Also, >80% respondents to the survey say that the leading causes of climate-related human impacts are the lack of (i) public awareness; (ii) investment and (iii) preparedness. The paper concludes by adding some suggestions that show how countries in Latin America may better cope with the impacts of Climate-sensitive Disasters

A global method for coupling transport with chemistry in heterogeneous porous media

Modeling reactive transport in porous media, using a local chemical equilibrium assumption, leads to a system of advection-diffusion PDE's coupled with algebraic equations. When solving this coupled system, the algebraic equations have to be solved at each grid point for each chemical species and at each time step. This leads to a coupled non-linear system. In this paper a global solution approach that enables to keep the software codes for transport and chemistry distinct is proposed. The method applies the Newton-Krylov framework to the formulation for reactive transport used in operator splitting. The method is formulated in terms of total mobile and total fixed concentrations and uses the chemical solver as a black box, as it only requires that on be able to solve chemical equilibrium problems (and compute derivatives), without having to know the solution method. An additional advantage of the Newton-Krylov method is that the Jacobian is only needed as an operator in a Jacobian matrix times vector product. The proposed method is tested on the MoMaS reactive transport benchmark.Comment: Computational Geosciences (2009) http://www.springerlink.com/content/933p55085742m203/?p=db14bb8c399b49979ba8389a3cae1b0f&pi=1

A Potential Role for Bat Tail Membranes in Flight Control

Wind tunnel tests conducted on a model based on the long-eared bat Plecotus auritus indicated that the positioning of the tail membrane (uropatagium) can significantly influence flight control. Adjusting tail position by increasing the angle of the legs ventrally relative to the body has a two-fold effect; increasing leg-induced wing camber (i.e., locally increased camber of the inner wing surface) and increasing the angle of attack of the tail membrane. We also used our model to examine the effects of flying with and without a tail membrane. For the bat model with a tail membrane increasing leg angle increased the lift, drag and pitching moment (nose-down) produced. However, removing the tail membrane significantly reduced the change in pitching moment with increasing leg angle, but it had no significant effect on the level of lift produced. The drag on the model also significantly increased with the removal of the tail membrane. The tail membrane, therefore, is potentially important for controlling the level of pitching moment produced by bats and an aid to flight control, specifically improving agility and manoeuvrability. Although the tail of bats is different from that of birds, in that it is only divided from the wings by the legs, it nonetheless, may, in addition to its prey capturing function, fulfil a similar role in aiding flight control

Physical mapping integrated with syntenic analysis to characterize the gene space of the long arm of wheat chromosome 1A

Background: Bread wheat (Triticum aestivum L.) is one of the most important crops worldwide and its production faces pressing challenges, the solution of which demands genome information. However, the large, highly repetitive hexaploid wheat genome has been considered intractable to standard sequencing approaches. Therefore the International Wheat Genome Sequencing Consortium (IWGSC) proposes to map and sequence the genome on a chromosome-by-chromosome basis. Methodology/Principal Findings: We have constructed a physical map of the long arm of bread wheat chromosome 1A using chromosome-specific BAC libraries by High Information Content Fingerprinting (HICF). Two alternative methods (FPC and LTC) were used to assemble the fingerprints into a high-resolution physical map of the chromosome arm. A total of 365 molecular markers were added to the map, in addition to 1122 putative unique transcripts that were identified by microarray hybridization. The final map consists of 1180 FPC based or 583 LTC based contigs. Conclusions/Significance: The physical map presented here marks an important step forward in mapping of hexaploid bread wheat. The map is orders of magnitude more detailed than previously available maps of this chromosome, and the assignment of over a thousand putative expressed gene sequences to specific map locations will greatly assist future functional studies. This map will be an essential tool for future sequencing of and positional cloning within chromosome 1A

The epidemiology of injuries across the weight-training sports

Background: Weight-training sports, including weightlifting, powerlifting, bodybuilding, strongman, Highland Games, and CrossFit, are weight-training sports that have separate divisions for males and females of a variety of ages, competitive standards, and bodyweight classes. These sports may be considered dangerous because of the heavy loads commonly used in training and competition. Objectives: Our objective was to systematically review the injury epidemiology of these weight-training sports, and, where possible, gain some insight into whether this may be affected by age, sex, competitive standard, and bodyweight class. Methods: We performed an electronic search using PubMed, SPORTDiscus, CINAHL, and Embase for injury epidemiology studies involving competitive athletes in these weight-training sports. Eligible studies included peer-reviewed journal articles only, with no limit placed on date or language of publication. We assessed the risk of bias in all studies using an adaption of the musculoskeletal injury review method. Results: Only five of the 20 eligible studies had a risk of bias score ≥75 %, meaning the risk of bias in these five studies was considered low. While 14 of the studies had sample sizes >100 participants, only four studies utilized a prospective design. Bodybuilding had the lowest injury rates (0.12–0.7 injuries per lifter per year; 0.24–1 injury per 1000 h), with strongman (4.5–6.1 injuries per 1000 h) and Highland Games (7.5 injuries per 1000 h) reporting the highest rates. The shoulder, lower back, knee, elbow, and wrist/hand were generally the most commonly injured anatomical locations; strains, tendinitis, and sprains were the most common injury type. Very few significant differences in any of the injury outcomes were observed as a function of age, sex, competitive standard, or bodyweight class. Conclusion: While the majority of the research we reviewed utilized retrospective designs, the weight-training sports appear to have relatively low rates of injury compared with common team sports. Future weight-training sport injury epidemiology research needs to be improved, particularly in terms of the use of prospective designs, diagnosis of injury, and changes in risk exposure

Daily life stress and the cortisol awakening response : testing the anticipation hypothesis

Acknowledgments We thank Paul Stewart for his contribution to data collection and Dr Matthew Jones for programming the handheld computers. Author Contributions Conceived and designed the experiments: WS DJP. Performed the experiments: DJP. Analyzed the data: WS. Wrote the paper: WS DJP.Peer reviewedPublisher PD