Angular distribution, kinetic energy distributions, and excitation functions of fast metastable oxygen fragments following electron impact of CO2

Dissociative excitation of CO2 by electron impact was studied using the methods of translational spectroscopy and angular distribution analysis. Earlier time of flight studies revealed two overlapping spectra, the slower of which was attributed to metastable CO(a3 pi) fragments. The fast peak is the focus of this study. Threshold energy, angular distribution, and improve time of flight measurements indicate that the fast peak actually consists of five overlapping features. The slowest of the five features is found to consist of metastable 0(5S) produced by predissociation of a sigma u + state of CO2 into 0(5S) + CO(a3 pi). Oxygen Rydberg fragments originating directly from a different sigma u + state are believed to make up the next fastest feature. Mechanisms for producing the three remaining features are discussed

Angular distributions and polarization fractions of helium resonance radiation (n 1P - 1 1S) in the extreme ultraviolet

Angular intensity distributions of helium (n 1P - 1 1S) resonance photons with respect to the exciting electron beam are presented. The angular intensity distributions were measured at selected electron impact energies from 25 eV (near threshold) to 150 eV. Polarization fractions (Pi) were obtained by analyzing the data in terms of the theoretical relation between angular intensity distribution and Pi, i.e. Iota (theta) = Iota (90) (1 - Pi sq cos theta). The experimental values for Pi are compared with recent theoretical results and with previous experimental values for the (3 1P - 2 1S) transition

Electromagnetic Compatibility Testing of Implantable Neurostimulators Exposed to Metal Detectors

This paper presents results of electromagnetic compatibility (EMC) testing of three implantable neurostimulators exposed to the magnetic fields emitted from several walk-through and hand-held metal detectors. The motivation behind this testing comes from numerous adverse event reports involving active implantable medical devices (AIMDs) and security systems that have been received by the Food and Drug Administration (FDA). EMC testing was performed using three neurostimulators exposed to the emissions from 12 walk-through metal detectors (WTMDs) and 32 hand-held metal detectors (HHMDs). Emission measurements were performed on all HHMDs and WTMDs and summary data is presented. Results from the EMC testing indicate possible electromagnetic interference (EMI) between one of the neurostimulators and one WTMD and indicate that EMI between the three neurostimulators and HHMDs is unlikely. The results suggest that worst case situations for EMC testing are hard to predict and testing all major medical device modes and setting parameters are necessary to understand and characterize the EMC of AIMDs

Quantifying CD4 receptor protein in two human CD4+ lymphocyte preparations for quantitative flow cytometry

In our previous study that characterized different human CD4+ lymphocyte preparations, it was found that both commercially available cryopreserved peripheral blood mononuclear cells (PBMC) and a commercially available lyophilized PBMC (Cyto-Trol™) preparation fulfilled a set of criteria for serving as biological calibrators for quantitative flow cytometry. However, the biomarker CD4 protein expression level measured for T helper cells from Cyto-Trol was about 16% lower than those for cryopreserved PBMC and fresh whole blood using flow cytometry and mass cytometry. A primary reason was hypothesized to be due to steric interference in anti- CD4 antibody binding to the smaller sized lyophilized control cells. Targeted multiple reaction monitoring (MRM) mass spectrometry (MS) is used to quantify the copy number of CD4 receptor protein per CD4+ lymphocyte. Scanning electron microscopy (SEM) is utilized to assist searching the underlying reasons for the observed difference in CD4 receptor copy number per cell determined by MRM MS and CD4 expression measured previously by flow cytometry. The copy number of CD4 receptor proteins on the surface of the CD4+ lymphocyte in cryopreserved PBMCs and in lyophilized control cells is determined to be (1.45 ± 0.09) × 105 and (0.85 ± 0.11) × 105, respectively, averaged over four signature peptides using MRM MS. In comparison with cryopreserved PBMCs, there are more variations in the CD4 copy number in lyophilized control cells determined based on each signature peptide. SEM images of CD4+ lymphocytes from lyophilized control cells are very different when compared to the CD4+ T cells from whole blood and cryopreserved PBMC. Because of the lyophilization process applied to Cyto-Trol control cells, a lower CD4 density value, defined as the copy number of CD4 receptors per CD4+ lymphocyte, averaged over three different production lots is most likely explained by the loss of the CD4 receptors on damaged and/or broken microvilli where CD4 receptors reside. Steric hindrance of antibody binding and the association of CD4 receptors with other biomolecules likely contribute significantly to the nearly 50% lower CD4 receptor density value for cryopreserved PBMC determined from flow cytometry compared to the value obtained from MRM MS.https://doi.org/10.1186/1559-0275-11-4

A Novel Frequency Analysis Method for Assessing Kir2.1 and Nav1.5 Currents

Voltage clamping is an important tool for measuring individual currents from an electrically active cell. However, it is difficult to isolate individual currents without pharmacological or voltage inhibition. Herein, we present a technique that involves inserting a noise function into a standard voltage step protocol, which allows one to characterize the unique frequency response of an ion channel at different step potentials. Specifically, we compute the fast Fourier transform for a family of current traces at different step potentials for the inward rectifying potassium channel, Kir2.1, and the channel encoding the cardiac fast sodium current, Nav1.5. Each individual frequency magnitude, as a function of voltage step, is correlated to the peak current produced by each channel. The correlation coefficient vs. frequency relationship reveals that these two channels are associated with some unique frequencies with high absolute correlation. The individual IV relationship can then be recreated using only the unique frequencies with magnitudes of high absolute correlation. Thus, this study demonstrates that ion channels may exhibit unique frequency responses

The fading of reported effectiveness. A meta-analysis of randomised controlled trials

BACKGROUND: The "real" effect size of a medical therapy is constant over time. In contrast, the effect size reported in randomised controlled trials (RCTs) may change over time because the sum of all kinds of bias influencing the reported effectiveness is not necessarily constant. As this would affect the validity of meta-analyses, we tested the hypothesis that the reported effect size decreases over time. Furthermore, we tested three hypotheses that would explain a possible change. METHODS: Because of well established outcome measures, the lipid-lowering drugs Pravastatin and Atorvastatin (serum low-density lipoprotein cholesterol, LDL-C) and the anti-glaucoma drugs Timolol and Latanoprost (intraocular pressure, IOP) were chosen for this investigation. Studies were identified by a standardized MEDLINE search. RCTs investigating the above identified medications administered as monotherapy, and in defined dosages, were included. Publication year, baseline (= pre-treatment value in the treatment group of interest) and post intervention means, number of patients and the assignment to experimental or control group were extracted for each study. RESULTS: A total of 625 citations were screened; 206 met the inclusion criteria. The reported effect size of Pravastatin (change of reported effect size in five years: -3.22% LDL-C, P < .0001), Timolol (-0.56 mmHg, P < .0001) and Latanoprost (-1.78 mmHg, P = .0074) decreased over time, while there was no significant change for Atorvastatin (+0.31% LDL-C, P = .8618). Multiple regression analysis showed that baseline values were the most important influencing factor; study size or treatment group did not play a significant role. CONCLUSION: The effectiveness of medical therapies reported in RCTs decreases over time in three of the four investigated pharmaceuticals, caused mainly by baseline differences. We call this phenomenon "fading of reported effectiveness". Under this condition the validity of a meta-analysis may be impaired. Therefore we propose to observe this phenomenon in future meta-analyses in order to guarantee a maximum of transparency

Molecular architecture and functional analysis of NetB, a pore-forming toxin from Clostridium perfringens

NetB is a pore-forming toxin produced by Clostridium perfringens and has been reported to play a major role in the pathogenesis of avian necrotic enteritis, a disease that has emerged due to the removal of antibiotics in animal feedstuffs. Here we present the crystal structure of the pore-form of NetB solved to 3.9Å. The heptameric assembly shares structural homology to the Staphylococcal α-hemolysin. However, the rim domain, a region that is thought to interact with the target cell membrane shows sequence and structural divergence leading to the alteration of a phosphocholine binding pocket found in the staphylococcal toxins. Consistent with the structure we show that NetB does not bind phosphocholine efficiently but instead interacts directly with cholesterol leading to enhanced oligomerisation and pore formation. Finally we have identified conserved and non-conserved amino acid positions within the rim loops that significantly affect binding and toxicity of NetB. These findings present new insights into the mode of action of these pore-forming toxins enabling the design of more effective control measures against necrotic enteritis and providing potential new tools to the field of bionanotechnology

Trial Publication after Registration in ClinicalTrials.Gov: A Cross-Sectional Analysis

Joseph Ross and colleagues examine publication rates of clinical trials and find low rates of publication even following registration in Clinicaltrials.gov

Systematic Review of the Empirical Evidence of Study Publication Bias and Outcome Reporting Bias

BACKGROUND: The increased use of meta-analysis in systematic reviews of healthcare interventions has highlighted several types of bias that can arise during the completion of a randomised controlled trial. Study publication bias has been recognised as a potential threat to the validity of meta-analysis and can make the readily available evidence unreliable for decision making. Until recently, outcome reporting bias has received less attention. METHODOLOGY/PRINCIPAL FINDINGS: We review and summarise the evidence from a series of cohort studies that have assessed study publication bias and outcome reporting bias in randomised controlled trials. Sixteen studies were eligible of which only two followed the cohort all the way through from protocol approval to information regarding publication of outcomes. Eleven of the studies investigated study publication bias and five investigated outcome reporting bias. Three studies have found that statistically significant outcomes had a higher odds of being fully reported compared to non-significant outcomes (range of odds ratios: 2.2 to 4.7). In comparing trial publications to protocols, we found that 40-62% of studies had at least one primary outcome that was changed, introduced, or omitted. We decided not to undertake meta-analysis due to the differences between studies. CONCLUSIONS: Recent work provides direct empirical evidence for the existence of study publication bias and outcome reporting bias. There is strong evidence of an association between significant results and publication; studies that report positive or significant results are more likely to be published and outcomes that are statistically significant have higher odds of being fully reported. Publications have been found to be inconsistent with their protocols. Researchers need to be aware of the problems of both types of bias and efforts should be concentrated on improving the reporting of trials

Adult Consequences of Late Adolescent Alcohol Consumption: A Systematic Review of Cohort Studies

In a systematic review of cohort studies of adolescent drinking and later outcomes, Jim McCambridge and colleagues show that although studies suggest links to worse adult physical and mental health and social consequences, existing evidence is of poor quality