Predicting the Activation States of the Muscles Governing Upper Esophageal Sphincter Relaxation and Opening

Copyright © 2016 the American Physiological SocietyThe swallowing muscles that influence upper esophageal sphincter (UES) opening are centrally controlled and modulated by sensory information. Activation and deactivation of neural inputs to these muscles, including the intrinsic cricopharyngeus (CP) and extrinsic submental (SM) muscles, results in their mechanical activation or deactivation, which changes the diameter of the lumen, alters the intraluminal pressure, and ultimately reduces or promotes flow of content. By measuring the changes in diameter, using intraluminal impedance, and the concurrent changes in intraluminal pressure, it is possible to determine when the muscles are passively or actively relaxing or contracting. From these “mechanical states” of the muscle, the neural inputs driving the specific motor behaviors of the UES can be inferred. In this study we compared predictions of UES mechanical states directly with the activity measured by electromyography (EMG). In eight subjects, pharyngeal pressure and impedance were recorded in parallel with CP- and SM-EMG activity. UES pressure and impedance swallow profiles correlated with the CP-EMG and SM-EMG recordings, respectively. Eight UES muscle states were determined by using the gradient of pressure and impedance with respect to time. Guided by the level and gradient change of EMG activity, mechanical states successfully predicted the activity of the CP muscle and SM muscle independently. Mechanical state predictions revealed patterns consistent with the known neural inputs activating the different muscles during swallowing. Derivation of “activation state” maps may allow better physiological and pathophysiological interpretations of UES function

Discrimination of dark matter models in future experiments

Phenomenological aspects of simple dark matter models are studied. We discuss ways to discriminate the dark matter models in future experiments. We find that the measurements of the branching fraction of the Higgs boson into two photons and the electric dipole moment of the electron as well as the direct detection experiments are quite useful in discriminating particle models of dark matter. We also discuss the prospects of finding new particles in dark sector at the LHC/ILC.Comment: 39 pages, 20 figures; v3 a typo in the Appendix A.1 is correcte

Modulation of Upper Esophageal Sphincter (UES) Relaxation and Opening During Volume Swallowing

“The final publication is available at Springer via http://dx.doi.org/10.1007/s00455-016-9744-4". This author accepted manuscript is made available following 12 month embargo from date of publication (17 Aug 2016) in accordance with the publisher's copyright policy.UES opening occurs following cricopharyngeus deactivation and submental muscle contraction causing hyolaryngeal elevation and UES distraction. During impedance manometry, the inverse of impedance (admittance) can be used to measure bolus presence and infer UES opening. We hypothesized that the temporal relationship between UES relaxation, opening and hyolaryngeal elevation would change with increasing bolus volume. Simultaneous intramuscular cricopharyngeal (CP) electromyography (EMG), surface submental EMG (SM-EMG), and high-resolution impedance manometry were recorded in eight (aged 27 ± 7 years, 5 M) healthy volunteers, while swallowing 0.9 % saline boluses of 2, 5, 10, and 20 ml. Data were exported and analyzed via Matlab. Statistical analysis comprised repeated measures one-way ANOVA and Pearson correlation. A P value of <0.05 was considered significant. Duration of CP deactivation increased at 20 ml volume (P < 0.001). UES relaxation and opening increased with increasing bolus volume (P < 0.001); however, overall duration of SM activation did not change. As UES opening occurs progressively earlier with increasing volumes, peak SM-EMG activity occurs relatively later (P < 0.001) and shifts from occurring before to following peak UES distention. During healthy swallowing, there is sensory modulation of cricopharyngeal and submental muscle activity. Intrabolus pressures, transmitted from the tongue base and pharynx, play a progressively more important role in sphincter opening with increasing volume. The findings may explain why some healthy elderly and patients with oropharyngeal dysphagia have difficulty swallowing larger while tolerating smaller bolus volumes

Long-term treatment with egg oral immunotherapy enhances sustained unresponsiveness that persists after cessation of therapy

We previously reported results of a randomized, placebo-controlled study of egg oral immunotherapy (eOIT), in which 27.5% of subjects achieved sustained unresponsiveness (SU) after 2 years. Here we report results of treatment through 4 years and long-term follow-up

A high-sensitivity electrochemiluminescence-based ELISA for the measurement of the oxidative stress biomarker, 3-nitrotyrosine, in human blood serum and cells

The generation of 3-nitrotyrosine, within proteins, is a post-translational modification resulting from oxidative or nitrative stress. It has been suggested that this modification could be used as a biomarker for inflammatory diseases. Despite the superiority of mass spectrometry-based determinations of nitrotyrosine, in a high-throughput clinical setting the measurement of nitrotyrosine by an enzyme-linked immunosorbent assay (ELISA) is likely to be more cost-effective. ELISAs offer an alternative means to detect nitrotyrosine, but many commercially available ELISAs are insufficiently sensitive to detect nitrotyrosine in healthy human serum. Here, we report the development, validation and clinical application of a novel electrochemiluminescence-based ELISA for nitrotyrosine which provides superior sensitivity (e.g. a 50-fold increase in sensitivity compared with one of the tested commercial colorimetric ELISAs). This nitrotyrosine ELISA has the following characteristics: a lower limit of quantitation of 0.04 nM nitrated albumin equivalents; intra- and inter-assay coefficients of variation of 6.5% and 11.3%, respectively; a mean recovery of 106 ± 3% and a mean linearity of 0.998 ± 0.001. Far higher nitration levels were measured in normal human blood cell populations when compared to plasma. Mass spectrometry was used to validate the new ELISA method. The analysis of the same set of chemically modified albumin samples using the ELISA method and mass spectrometry showed good agreement for the relative levels of nitration present in each sample. The assay was applied to serum samples from patients undergoing elective surgery which induces the human inflammatory response. Matched samples were collected before and one day after surgery. An increase in nitration was detected following surgery (median (IQR): 0.59 (0.00–1.34) and 0.97 (0.00–1.70) nitrotyrosine (fmol of nitrated albumin equivalents/mg protein) for pre- and post-surgery respectively. The reported assay is suitable for nitrotyrosine determination in patient serum samples, and may also be applicable as a means to determine oxidative stress in primary and cultured cell populations

A pragmatic harm reduction approach to manage a large outbreak of wound botulism in people who inject drugs, Scotland 2015

Abstract Background People who inject drugs (PWID) are at an increased risk of wound botulism, a potentially fatal acute paralytic illness. During the first 6 months of 2015, a large outbreak of wound botulism was confirmed among PWID in Scotland, which resulted in the largest outbreak in Europe to date. Methods A multidisciplinary Incident Management Team (IMT) was convened to conduct an outbreak investigation, which consisted of enhanced surveillance of cases in order to characterise risk factors and identify potential sources of infection. Results Between the 24th of December 2014 and the 30th of May 2015, a total of 40 cases were reported across six regions in Scotland. The majority of the cases were male, over 30 and residents in Glasgow. All epidemiological evidence suggested a contaminated batch of heroin or cutting agent as the source of the outbreak. There are significant challenges associated with managing an outbreak among PWID, given their vulnerability and complex addiction needs. Thus, a pragmatic harm reduction approach was adopted which focused on reducing the risk of infection for those who continued to inject and limited consequences for those who got infected. Conclusions The management of this outbreak highlighted the importance and need for pragmatic harm reduction interventions which support the addiction needs of PWID during an outbreak of spore-forming bacteria. Given the scale of this outbreak, the experimental learning gained during this and similar outbreaks involving spore-forming bacteria in the UK was collated into national guidance to improve the management and investigation of future outbreaks among PWID

Hot nanoindentation in inert environments

An instrument capable of performing nanoindentation at temperatures up to 500 °C in inert atmospheres, including partial vacuum and gas near atmospheric pressures, is described. Technical issues associated with the technique (such as drift and noise) and the instrument (such as tip erosion and radiative heating of the transducer) are identified and addressed. Based on these considerations, preferred operation conditions are identified for testing on various materials. As a proof-of-concept demonstration, the hardness and elastic modulus of three materials are measured: fused silica (nonoxidizing), aluminum, and copper (both oxidizing). In all cases, the properties match reasonably well with published data acquired by more conventional test methods.United States. Office of Naval Research (Contract No. N00014-08-1-0312)Massachusetts Institute of Technology. Institute for Soldier Nanotechnologie

National contributions to climate change due to historical emissions of carbon dioxide, methane, and nitrous oxide since 1850

Anthropogenic emissions of carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O) have made significant contributions to global warming since the pre-industrial period and are therefore targeted in international climate policy. There is substantial interest in tracking and apportioning national contributions to climate change and informing equitable commitments to decarbonisation. Here, we introduce a new dataset of national contributions to global warming caused by historical emissions of carbon dioxide, methane, and nitrous oxide during the years 1851–2021, which are consistent with the latest findings of the IPCC. We calculate the global mean surface temperature response to historical emissions of the three gases, including recent refinements which account for the short atmospheric lifetime of CH4. We report national contributions to global warming resulting from emissions of each gas, including a disaggregation to fossil and land use sectors. This dataset will be updated annually as national emissions datasets are updated