Mechanisms of Esophago-Pharyngeal Acid Regurgitation in Human Subjects

Esophago-pharyngeal regurgitation is implicated in various otolaryngologic and respiratory disorders. The pathophysiological mechanisms causing regurgitation are still largely unknown

British Valued Life Activities Scale [British VLAs]

Background The Valued Life Activities Scale (VLAs) measures difficulty in daily activities and social participation. With various versions involving a different number of items, we have linguistically and culturally adopted the full VLAs (33-items) and psychometrically tested it in adults with rheumatic and musculoskeletal diseases in the United Kingdom. Methods Participants with Rheumatoid Arthritis, Ankylosing Spondylitis, Chronic Pain/ Fibromyalgia, Chronic Hand/ Upper Limb Conditions, Osteoarthritis, Systemic Lupus, Systemic Sclerosis and Primary Sjogren’s Syndrome were recruited from out-patient clinics in National Health Service Hospitals, General Practice and patient organisations in the UK. Phase1 involved linguistic and cultural adaptation: forward translation to British English; synthesis; expert panel review and cognitive debriefing interviews. In Phase2 participants completed postal questionnaires to assess internal construct validity using (i) Confirmatory Factor Analysis (CFA) (ii) Mokken scaling and (iii) Rasch model. Results Responders (n = 1544) had mean age of 59 years (SD13.3) and 77.2% women. A CFA failed to support a total score from the 33-items (Chi Square 3552:df 464: p < 0.0001). Mokken scaling indicated a strong non-parametric association between items. Fit to the Rasch model indicated that the VLAs was characterised by multidimensionality and item misfit, which may have been influenced by clusters of residual item correlations. An item banking approach resolved a 25-item calibrated set whose application could accommodate the ‘does not apply to me’ response option. Conclusions The UK version of the VLAs failed to satisfy classical and modern psychometric standards for complete item sets. However, as the scale is not usually applied in complete format, an item bank approach calibrated 25 items with fit to the Rasch model. Suitable Computer Adaptive Testing (CAT) software could implement the item set, giving patients the choice of whether an item applies to them, or not

Universality, limits and predictability of gold-medal performances at the Olympic Games

Inspired by the Games held in ancient Greece, modern Olympics represent the world's largest pageant of athletic skill and competitive spirit. Performances of athletes at the Olympic Games mirror, since 1896, human potentialities in sports, and thus provide an optimal source of information for studying the evolution of sport achievements and predicting the limits that athletes can reach. Unfortunately, the models introduced so far for the description of athlete performances at the Olympics are either sophisticated or unrealistic, and more importantly, do not provide a unified theory for sport performances. Here, we address this issue by showing that relative performance improvements of medal winners at the Olympics are normally distributed, implying that the evolution of performance values can be described in good approximation as an exponential approach to an a priori unknown limiting performance value. This law holds for all specialties in athletics-including running, jumping, and throwing-and swimming. We present a self-consistent method, based on normality hypothesis testing, able to predict limiting performance values in all specialties. We further quantify the most likely years in which athletes will breach challenging performance walls in running, jumping, throwing, and swimming events, as well as the probability that new world records will be established at the next edition of the Olympic Games.Comment: 8 pages, 3 figures, 1 table. Supporting information files and data are available at filrad.homelinux.or

The Pioneer Anomaly

Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20-70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of the Newton's gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living Reviews in Relativit

Galaxy Harassment and the Evolution of Clusters of Galaxies

Disturbed spiral galaxies with high rates of star formation pervaded clusters of galaxies just a few billion years ago, but nearby clusters exclude spirals in favor of ellipticals. ``Galaxy harassment" (frequent high speed galaxy encounters) drives the morphological transformation of galaxies in clusters, provides fuel for quasars in subluminous hosts and leaves detectable debris arcs. Simulated images of harassed galaxies are strikingly similar to the distorted spirals in clusters at $z \sim 0.4$ observed by the Hubble Space Telescope.Comment: Submitted to Nature. Latex file, 7 pages, 10 photographs in gif and jpeg format included. 10 compressed postscript figures and text available using anonymous ftp from ftp://ftp-hpcc.astro.washington.edu/pub/hpcc/moore/ (mget *) Also available at http://www-hpcc.astro.washington.edu/papers

Associations between age and sleep apnea risk among newborn infants

ObjectiveAmong older children, sleep‐disordered breathing (SDB) is associated with measurable neurocognitive consequences. However, diagnostic SDB thresholds are lacking for infants < 12 months. We sought to evaluate the relationship between SDB indices, gestational age (GA), and postmenstrual age (PMA) for infants who underwent clinically‐indicated polysomnograms at a tertiary care center.MethodsEvery infant < 3‐months chronological age whose first clinically‐indicated polysomnogram was between 2/2012 and 2/2017 was included. Linear regression was used to evaluate associations between apnea‐hypopnea index (AHI), obstructive‐apnea index (OAI), and GA and PMA for infants with and without obvious clinical risk factors for SDB (eg, micrognathia and cleft palate).ResultsFor 53 infants without obvious SDB risk factors (GA 35.6 ± 4.5 weeks; PMA 41.2 ± 4.0 weeks), mean AHI was 27 ± 18 and OAI 2.9 ± 4.5. There was a weak inverse relationship between AHI and PMA (r2 = 0.12, P = 0.01), but AHI was not predicted by GA (r2 = 0.04, P = 0.13). Conversely, OAI was more strongly associated with GA (r2 = 0.33, P < 0.0001) than PMA (r2 = 0.08, P = 0.036). For 28 infants with congenital structural anomalies that predispose to SDB (GA 38.0 ± 3.1 weeks, PMA 43.1 ± 3.3 weeks, AHI 37.7 ± 30, OAI 8.2 ± 11.8), neither AHI nor OAI were related to PMA or GA.ConclusionsAmong infants who received clinically‐indicated polysomnograms but did not have obvious structural risk for SDB, AHI declined with advancing PMA, but obstructive‐apnea was best predicted by prematurity. In contrast, the SDB risk did not improve with increasing GA or PMA for infants with congenital structural risk factors; such infants may not outgrow their risk for SDB.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150552/1/ppul24354_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150552/2/ppul24354.pd

Muscle fiber conduction velocity is more affected after eccentric than concentric exercise

It has been shown that mean muscle fiber conduction velocity (CV) can be acutely impaired after eccentric exercise. However, it is not known whether this applies to other exercise modes. Therefore, the purpose of this experiment was to compare the effects of eccentric and concentric exercises on CV, and amplitude and frequency content of surface electromyography (sEMG) signals up to 24 h post-exercise. Multichannel sEMG signals were recorded from biceps brachii muscle of the exercised arm during isometric maximal voluntary contraction (MVC) and electrically evoked contractions induced by motor-point stimulation before, immediately after and 2 h after maximal eccentric (ECC group, N = 12) and concentric (CON group, N = 12) elbow flexor exercises. Isometric MVC decreased in CON by 21.7 ± 12.0% (± SD, p < 0.01) and by 30.0 ± 17.7% (p < 0.001) in ECC immediately post-exercise when compared to baseline. At 2 h post-exercise, ECC showed a reduction in isometric MVC by 24.7 ± 13.7% (p < 0.01) when compared to baseline, while no significant reduction (by 8.0 ± 17.0%, ns) was observed in CON. Similarly, reduction in CV was observed only in ECC both during the isometric MVC (from baseline of 4.16 ± 0.3 to 3.43 ± 0.4 m/s, p < 0.001) and the electrically evoked contractions (from baseline of 4.33 ± 0.4 to 3.82 ± 0.3 m/s, p < 0.001). In conclusion, eccentric exercise can induce a greater and more prolonged reduction in muscle force production capability and CV than concentric exercis

Targeting uracil-DNA glycosylases for therapeutic outcomes using insights from virus evolution

Ung-type uracil-DNA glycosylases are frontline defenders of DNA sequence fidelity in bacteria, plants, and animals; Ungs also directly assist both innate and humoral immunity. Critically important in viral pathogenesis, whether acting for or against viral DNA persistence, Ungs also have therapeutic relevance to cancer, microbial, and parasitic diseases. Ung catalytic specificity is uniquely conserved, yet selective antiviral drugging of the Ung catalytic pocket is tractable. However, more promising precision therapy approaches present themselves via insights from viral strategies, including sequestration or adaptation of Ung for non-canonical roles. A universal Ung inhibition mechanism, converged upon by unrelated viruses, could also inform design of compounds to inhibit specific distinct Ungs. Extrapolating current developments, the character of such novel chemical entities is proposed

Incidence rates of in-hospital carpal tunnel syndrome in the general population and possible associations with marital status

<p>Abstract</p> <p>Background</p> <p>Carpal tunnel syndrome (CTS) is a socially relevant condition associated with biomechanical risk factors. We evaluated age-sex-specific incidence rates of in-hospital cases of CTS in central/northern Italy and explored relations with marital status.</p> <p>Methods</p> <p>Seven regions were considered (overall population, 14.9 million) over 3–6-year periods between 1997 and 2002 (when out-of-hospital CTS surgery was extremely rare). Incidence rates of in-hospital cases of CTS were estimated based on 1) codified demographic, diagnostic and intervention data in obligatory discharge records from all Italian public/private hospitals, archived (according to residence) on regional databases; 2) demographic general population data for each region. We compared (using the χ_scoretest) age-sex-specific rates between married, unmarried, divorced and widowed subsets of the general population. We calculated standardized incidence ratios (SIRs) for married/unmarried men and women.</p> <p>Results</p> <p>Age-standardized incidence rates (per 100,000 person-years) of in-hospital cases of CTS were 166 in women and 44 in men (106 overall). Married subjects of both sexes showed higher age-specific rates with respect to unmarried men/women. SIRs were calculated comparing married vs unmarried rates of both sexes: 1.59 (95% confidence interval [95% CI], 1.57–1.60) in women, and 1.42 (95% CI, 1.40–1.45) in men. As compared with married women/men, widows/widowers both showed 2–3-fold higher incidence peaks during the fourth decade of life (beyond 50 years of age, widowed subjects showed similar trends to unmarried counterparts).</p> <p>Conclusion</p> <p>This large population-based study illustrates distinct age-related trends in men and women, and also raises the question whether marital status could be associated with CTS in the general population.</p

The semi-classical expansion and resurgence in gauge theories: new perturbative, instanton, bion, and renormalon effects

We study the dynamics of four dimensional gauge theories with adjoint fermions for all gauge groups, both in perturbation theory and non-perturbatively, by using circle compactification with periodic boundary conditions for the fermions. There are new gauge phenomena. We show that, to all orders in perturbation theory, many gauge groups are Higgsed by the gauge holonomy around the circle to a product of both abelian and nonabelian gauge group factors. Non-perturbatively there are monopole-instantons with fermion zero modes and two types of monopole-anti-monopole molecules, called bions. One type are "magnetic bions" which carry net magnetic charge and induce a mass gap for gauge fluctuations. Another type are "neutral bions" which are magnetically neutral, and their understanding requires a generalization of multi-instanton techniques in quantum mechanics - which we refer to as the Bogomolny-Zinn-Justin (BZJ) prescription - to compactified field theory. The BZJ prescription applied to bion-anti-bion topological molecules predicts a singularity on the positive real axis of the Borel plane (i.e., a divergence from summing large orders in peturbation theory) which is of order N times closer to the origin than the leading 4-d BPST instanton-anti-instanton singularity, where N is the rank of the gauge group. The position of the bion--anti-bion singularity is thus qualitatively similar to that of the 4-d IR renormalon singularity, and we conjecture that they are continuously related as the compactification radius is changed. By making use of transseries and Ecalle's resurgence theory we argue that a non-perturbative continuum definition of a class of field theories which admit semi-classical expansions may be possible.Comment: 112 pages, 7 figures; v2: typos corrected, discussion of supersymmetric models added at the end of section 8.1, reference adde