New insights into the cardiorespiratory physiology of weaned southern elephant seals (Mirounga leonina)

Southern elephant seal (Mirounga leonina) pups must strike a balance between conserving energy during their post-weaning fast and simultaneously developing diving abilities to attain nutritional independence. Little is known about environmental influences on cardiorespiratory patterns, hence energy use, throughout the 6 week fast. Continuous heart rates were recorded for free-ranging, newly weaned southern elephant seals using heart rate time-depth recorders for 5-9 days at Sub-Antarctic Macquarie Island, during October 1994 (n = 1), 1995 (n = 4) and 1996 (n = 1). Daytime observations of respiration and behaviour were made throughout. We present the first instance of synchronous heart rate traces recorded simultaneously for individual weaners. Generalized additive models revealed that a sinusoidal pattern of diurnal heart rate elevation and nocturnal depression was evident in all seals and, on at least one occasion, a conspicuous break in this pattern coincided with an extreme cold weather event. Seals in this study were capable of considerable cardiorespiratory control and regularly demonstrated bradycardia during periods of resting apnoea. Apnoeic duration ranged from 33 to 291 s (mean 134 s). Apnoeic heart rates (mean 67 ± 15 beats min(-1), range 40-114 beats min(-1)) were on average 19.7% lower than those exhibited during periods of eupnoea (mean 83 ± 15 beats min(-1), range 44-124 beats min(-1)). The early development of the cardiorespiratory response is characterized by arrhythmic heart and respiration rates. The strong temporal patterns observed are being driven by the opposing requirements of maximizing time spent fasting in order to develop diving capabilities and of maximizing departure mass. This pilot study has highlighted a potentially large effect of ambient weather conditions on newly weaned southern elephant seal cardiorespiratory activity. Given the increasing westerlies and more erratic and increasing storminess associated with the Southern Annular Mode predicted in the Southern Ocean, the patterns observed here warrant further investigation

Popovic, RF Cavities Loaded with Dielectric for Muon Facilities RF CAVITIES LOADED WITH DIELECTRIC FOR MUON FACILITIES

Abstract This paper discusses RF cavities loaded with dielectric material that could be used in various muon collider facilities. Most of the existing pill-box cavity designs are too large in diameter to fit efficiently in the current cooling lattice designs. The paper describes novel compact dielectric loaded RF cavities designs that fit efficiently in muon cooling lattices and allow multifrequency cavity designs in the same size cavity by changing the dielectric constant or size. The paper describes the designs of 400 and 800 MHz cavities for the (HCC) helical cooling channel. In addition to the use of the dielectric to reduce the radial size of gas-filled cavities in helical cooling channels, dielectric-loading has the potential use in vacuum cavities for suppression of dark current emission. Cavities that can be used for the phase rotation channel in the front end of a muon collider or neutrino factory are also presented

The Case for a Muon Collider Higgs Factory

We propose the construction of a compact Muon Collider Higgs Factory. Such a machine can produce up to \sim 14,000 at 8\times 10^{31} cm^-2 sec^-1 clean Higgs events per year, enabling the most precise possible measurement of the mass, width and Higgs-Yukawa coupling constants.Comment: Supporting letter for the document: "Muon Collider Higgs Factory for Smowmass 2013", A White Paper submitted to the 2013 U.S. Community Summer Study of the Division of Particles and Fields of the American Physical Society, Y. Alexahin, et. al, FERMILAB-CONF-13-245-T (July, 2013

Methods of the ITC Four Country Smoking and Vaping Survey, wave 1 (2016)

AIM: To describe the methods of the 2016 International Tobacco Control (ITC) Four Country Smoking and Vaping (4CV) Survey, conducted in 2016 in Australia (AU), Canada (CA), England (EN) and the United States (US). METHODS: The respondents were cigarette smokers, former smokers (quit within the previous 2 years), and at-least-weekly vapers, aged 18 years and older. Eligible cohort members from the ITC Four Country Survey (4C) were retained. New respondents were sampled by commercial firms from their panels. Where possible, ages 18-24 and vapers were oversampled. Data were collected online, and respondents were remunerated. Survey weights were calibrated to benchmarks from nationally representative surveys. RESULTS: Response rates by country for new recruits once invited ranged from 15.2 to 49.6%. Sample sizes for smokers/former smokers were 1504 in AU, 3006 in CA, 3773 in EN and 2239 in the US. Sample sizes for additional vapers were 727 in CA, 551 in EN and 494 in the US. CONCLUSION: The International Tobacco Control Four Country Smoking and Vaping Survey design and data collection methods allow analyses to examine prospectively the use of cigarettes and nicotine vaping products in jurisdictions with different regulatory policies. The effects on the sampling designs and response quality of recruiting the respondents from commercial panels are mitigated by the use of demographic and geographic quotas in sampling; by quality control measures; and by the construction of survey weights taking into account smoking/vaping status, sex, age, education and geography

Incident vertebral fractures and risk factors in the first three years following glucocorticoid initiation among pediatric patients with rheumatic disorders

Vertebral fractures are an important yet underrecognized manifestation of osteoporosis in children with chronic, glucocorticoid-treated illnesses. Our goal was to determine the incidence and clinical predictors of vertebral fractures in the 3 years following glucocorticoid initiation among pediatric patients with rheumatic disorders. Incident vertebral fractures were evaluated according to the Genant semiquantitative method on lateral radiographs at baseline and then annually in the 3 years following glucocorticoid initiation. Extended Cox models were used to assess the association between vertebral fractures and clinical risk predictors. A total of 134 children with rheumatic disorders were enrolled in the study (mean ± standard deviation (SD) age 9.9 ± 4.4 years; 65% girls). The unadjusted vertebral fracture incidence rate was 4.4 per 100 person-years, with a 3-year incidence proportion of 12.4%. The highest annual incidence occurred in the first year (6.0%; 95% confidence interval (CI) 2.9% to 11.7%). Almost one-half of the patients with fractures were asymptomatic. Every 0.5 mg/kg increase in average daily glucocorticoid (prednisone equivalents) dose was associated with a twofold increased fracture risk (hazard ratio (HR) 2.0; 95% CI 1.1 to 3.5). Other predictors of increased vertebral fracture risk included: (1) increases in disease severity scores between baseline and 12 months; (2) increases in body mass index Z-scores in the first 6 months of each 12-month period preceding the annual fracture assessment; and (3) decreases in lumbar spine bone mineral density Z-scores in the first 6 months of glucocorticoid therapy. As such, we observed that a clinically significant number of children with rheumatic disorders developed incident vertebral fractures in the 3 years following glucocorticoid initiation. Almost one-half of the children were asymptomatic and thereby would have been undiagnosed in the absence of radiographic monitoring. In addition, discrete clinical predictors of incident vertebral fractures were evident early in the course of glucocorticoid therapy

Hyperimmune immunoglobulin for hospitalised patients with COVID-19 (ITAC): a double-blind, placebo-controlled, phase 3, randomised trial

BACKGROUND: Passive immunotherapy using hyperimmune intravenous immunoglobulin (hIVIG) to SARS-CoV-2, derived from recovered donors, is a potential rapidly available, specific therapy for an outbreak infection such as SARS-CoV-2. Findings from randomised clinical trials of hIVIG for the treatment of COVID-19 are limited. METHODS: In this international randomised, double-blind, placebo-controlled trial, hospitalised patients with COVID-19 who had been symptomatic for up to 12 days and did not have acute end-organ failure were randomly assigned (1:1) to receive either hIVIG or an equivalent volume of saline as placebo, in addition to remdesivir, when not contraindicated, and other standard clinical care. Randomisation was stratified by site pharmacy; schedules were prepared using a mass-weighted urn design. Infusions were prepared and masked by trial pharmacists; all other investigators, research staff, and trial participants were masked to group allocation. Follow-up was for 28 days. The primary outcome was measured at day 7 by a seven-category ordinal endpoint that considered pulmonary status and extrapulmonary complications and ranged from no limiting symptoms to death. Deaths and adverse events, including organ failure and serious infections, were used to define composite safety outcomes at days 7 and 28. Prespecified subgroup analyses were carried out for efficacy and safety outcomes by duration of symptoms, the presence of anti-spike neutralising antibodies, and other baseline factors. Analyses were done on a modified intention-to-treat (mITT) population, which included all randomly assigned participants who met eligibility criteria and received all or part of the assigned study product infusion. This study is registered with ClinicalTrials.gov, NCT04546581. FINDINGS: From Oct 8, 2020, to Feb 10, 2021, 593 participants (n=301 hIVIG, n=292 placebo) were enrolled at 63 sites in 11 countries; 579 patients were included in the mITT analysis. Compared with placebo, the hIVIG group did not have significantly greater odds of a more favourable outcome at day 7; the adjusted OR was 1·06 (95% CI 0·77–1·45; p=0·72). Infusions were well tolerated, although infusion reactions were more common in the hIVIG group (18·6% vs 9·5% for placebo; p=0·002). The percentage with the composite safety outcome at day 7 was similar for the hIVIG (24%) and placebo groups (25%; OR 0·98, 95% CI 0·66–1·46; p=0·91). The ORs for the day 7 ordinal outcome did not vary for subgroups considered, but there was evidence of heterogeneity of the treatment effect for the day 7 composite safety outcome: risk was greater for hIVIG compared with placebo for patients who were antibody positive (OR 2·21, 95% CI 1·14–4·29); for patients who were antibody negative, the OR was 0·51 (0·29–0·90; pinteraction=0·001). INTERPRETATION: When administered with standard of care including remdesivir, SARS-CoV-2 hIVIG did not demonstrate efficacy among patients hospitalised with COVID-19 without end-organ failure. The safety of hIVIG might vary by the presence of endogenous neutralising antibodies at entry. FUNDING: US National Institutes of Health