Age, gender, neck circumference, and Epworth sleepiness scale do not predict obstructive sleep apnea (OSA) in moderate to severe chronic obstructive pulmonary disease (COPD): The challenge to predict OSA in advanced COPD

The combination of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) is associated with substantial morbidity and mortality. We hypothesized that predictors of OSA among patients with COPD may be distinct from OSA in the general population. Therefore, we investigated associations between traditional OSA risk factors (e.g. age), and sleep questionnaires [e.g. Epworth Sleepiness Scale] in 44 patients with advanced COPD. As a second aim we proposed a pilot, simplified screening test for OSA in patients with COPD. In a prospective, observational study of patients enrolled in the UCSD Pulmonary Rehabilitation Program we collected baseline characteristics, cardiovascular events (e.g. atrial fibrillation), and sleep questionnaires [e.g. Pittsburgh Sleep Quality Index (PSQI)]. For the pilot questionnaire, a BMI =25 kg/m2 and the presence of cardiovascular disease were used to construct the pilot screening test. Male: 59%; OSA 66%. FEV1 (mean ± SD) = 41.0±18.2% pred., FEV1/FVC = 41.5±12.7%]. Male gender, older age, and large neck circumference were not associated with OSA. Also, Epworth Sleepiness Scale and the STOP-Bang questionnaire were not associated with OSA in univariate logistic regression. In contrast, BMI =25 kg/m2 (OR = 3.94, p = 0.04) and diagnosis of cardiovascular disease (OR = 5.06, p = 0.03) were significantly associated with OSA [area under curve (AUC) = 0.74]. The pilot COPD-OSA test (OR = 5.28, p = 0.05) and STOP-Bang questionnaire (OR = 5.13, p = 0.03) were both associated with OSA in Receiver Operating Characteristics (ROC) analysis. The COPD-OSA test had the best AUC (0.74), sensitivity (92%), and specificity (83%). A tenfold cross-validation validated our results. We found that traditional OSA predictors (e.g. gender, Epworth score) did not perform well in patients with more advanced COPD. Our pilot test may be an easy to implement instrument to screen for OSA. However, a larger validation study is necessary before further clinical implementation is warranted

A Separation Logic for Fictional Sequential Consistency

To improve performance, modern multiprocessors and pro- gramming languages typically implement relaxed memory models that do not require all processors/threads to observe memory operations in the same order. To relieve programmers from having to reason directly about these relaxed behaviors, languages often provide efficient synchro- nization primitives and concurrent data structures with stronger high- level guarantees about memory reorderings. For instance, locks usually ensure that when a thread acquires a lock, it can observe all memory operations of the releasing thread, prior to the release. When used cor- rectly, these synchronization primitives and data structures allow clients to recover a fiction of a sequentially consistent memory model. In this paper we propose a new proof system, iCAP-TSO, that captures this fiction formally, for a language with a TSO memory model. The logic supports reasoning about libraries that directly exploit the relaxed memory model to achieve maximum efficiency. When these libraries pro- vide sufficient guarantees, the logic hides the underlying complexity and admits standard separation logic rules for reasoning about their more high-level clients

Effect of an antenatal diet and lifestyle intervention and maternal BMI on cord blood DNA methylation in infants of overweight and obese women: The LIMIT Randomised Controlled Trial

Background: To investigate the effect of an antenatal diet and lifestyle intervention, and maternal prepregnancy overweight or obesity, on infant cord blood DNA methylation. Methods: We measured DNA methylation in 645 cord blood samples from participants in the LIMIT study (an antenatal diet and lifestyle intervention for women with early pregnancy BMI 25.0 kg/m2) using the Illumina 450K BeadChip array, and tested for any differential methylation related to the intervention, and to maternal early pregnancy BMI. We also analysed differential methylation in relation to selected candidate genes. Results: No CpG sites were significantly differentially methylated in relation to either the diet and lifestyle intervention, or with maternal early pregnancy BMI. There was no significant differential methylation in any of the selected genes related to the intervention, or to maternal BMI. Conclusion: We found no evidence of an effect of either antenatal diet and lifestyle, or of maternal early pregnancy BMI, on cord blood DNA methylation.Jennie Louise, Andrea R. Deussen, Berthold Koletzko, Julie Owens, Richard Saffery, Jodie M. Dod

Machine-learning-based calving prediction from activity, lying, and ruminating behaviors in dairy cattle

The objective of this study was to use automated activity, lying, and rumination monitors to characterize prepartum behavior and predict calving in dairy cattle. Data were collected from 20 primiparous and 33 multiparous Holstein dairy cattle from September 2011 to May 2013 at the University of Kentucky Coldstream Dairy. The HR Tag (SCR Engineers Ltd., Netanya, Israel) automatically collected neck activity and rumination data in 2-h increments. The IceQube (IceRobotics Ltd., South Queensferry, United Kingdom) automatically collected number of steps, lying time, standing time, number of transitions from standing to lying (ly-. ing bouts), and total motion, summed in 15-min increments. IceQube data were summed in 2-h increments to match HR Tag data. All behavioral data were collected for 14 d before the predicted calving date. Retrospective data analysis was performed using mixed linear models to examine behavioral changes by day in the 14 d before calving. Bihourly behavioral differences from baseline values over the 14 d before calving were also evaluated using mixed linear models. Changes in daily rumination time, total motion, lying time, and lying bouts occurred in the 14 d before calving. In the bihourly analysis, extreme values for all behaviors occurred in the final 24 h, indicating that the monitored behaviors may be useful in calving prediction. To determine whether technologies were useful at predicting calving, random forest, linear discriminant analysis, and neural network machine -learning techniques were constructed and implemented using R version 3.1.0 (R Foundation for Statistical Computing, Vienna, Austria). These methods were used on variables from each technology and all combined variables from both technologies. A neural network analysis that combined variables from both technologies at the daily level yielded 100.0% sen-sitivity and 86.8% specificity. A neural network analysis that combined variables from both technologies in bihourly increments was used to identify 2-h periods in the 8 h before calving with 82.8% sensitivity and 80.4% specificity. Changes in behavior and machine-learning alerts indicate that commercially marketed behavioral monitors may have calving prediction potential

A new calibrated sunspot group series since 1749: statistics of active day fractions

Although the sunspot-number series have existed since the mid-19th century, they are still the subject of intense debate, with the largest uncertainty being related to the "calibration" of the visual acuity of individual observers in the past. Daisy-chain regression methods are applied to inter-calibrate the observers which may lead to significant bias and error accumulation. Here we present a novel method to calibrate the visual acuity of the key observers to the reference data set of Royal Greenwich Observatory sunspot groups for the period 1900-1976, using the statistics of the active-day fraction. For each observer we independently evaluate their observational thresholds [S_S] defined such that the observer is assumed to miss all of the groups with an area smaller than S_S and report all the groups larger than S_S. Next, using a Monte-Carlo method we construct, from the reference data set, a correction matrix for each observer. The correction matrices are significantly non-linear and cannot be approximated by a linear regression or proportionality. We emphasize that corrections based on a linear proportionality between annually averaged data lead to serious biases and distortions of the data. The correction matrices are applied to the original sunspot group records for each day, and finally the composite corrected series is produced for the period since 1748. The corrected series displays secular minima around 1800 (Dalton minimum) and 1900 (Gleissberg minimum), as well as the Modern grand maximum of activity in the second half of the 20th century. The uniqueness of the grand maximum is confirmed for the last 250 years. It is shown that the adoption of a linear relationship between the data of Wolf and Wolfer results in grossly inflated group numbers in the 18th and 19th centuries in some reconstructions

Zanamivir susceptibility monitoring and characterization of influenza virus clinical isolates obtained during phase II clinical efficacy studies

Zanamivir is a highly selective neuraminidase (NA) inhibitor with demonstrated clinical efficacy against influenza A and B virus infections. In phase II clinical efficacy trials (NAIB2005 and NAIB2008), virological substudies showed mean reductions in virus shedding after 24 h of treatment of 1.5 to 2.0 log(10) 50% tissue culture infective doses compared to a placebo, with no reemergence of virus after the completion of therapy. Paired isolates (n = 41) obtained before and during therapy with zanamivir demonstrated no shifts in susceptibility to zanamivir when measured by NA assays, although for a few isolates NA activity was too low to evaluate. In plaque reduction assays in MDCK cells, the susceptibility of isolates to zanamivir was extremely variable even at baseline and did not correlate with the speed of resolution of virus shedding. Isolates with apparent limited susceptibility to zanamivir by plaque reduction proved highly susceptible in vivo in the ferret model. Further sequence analysis of paired isolates revealed no changes in the hemagglutinin and NA genes in the majority of isolates. The few changes observed were all natural variants. No amino acid changes that had previously been identified in vitro as being involved with reduced susceptibility to zanamivir were observed. These studies highlighted problems associated with monitoring susceptibility to NA inhibitors in the clinic, in that no reliable cell-based assay is available. At present the NA assay is the best available predictor of susceptibility to NA inhibitors in vivo, as measured in the validated ferret model of infection

Cold Nuclear Matter Effects on Dijet Productions in Relativistic Heavy-ion Reactions at LHC

We investigate the cold nuclear matter(CNM) effects on dijet productions in high-energy nuclear collisions at LHC with the next-to-leading order perturbative QCD. The nuclear modifications for dijet angular distributions, dijet invariant mass spectra, dijet transverse momentum spectra and dijet momentum imbalance due to CNM effects are calculated by incorporating EPS, EKS, HKN and DS param-etrization sets of parton distributions in nucleus . It is found that dijet angular distributions and dijet momentum imbalance are insensitive to the initial-state CNM effects and thus provide optimal tools to study the final-state hot QGP effects such as jet quenching. On the other hand, the invariant mass spectra and the transverse momentum spectra of dijet are generally enhanced in a wide region of the invariant mass or transverse momentum due to CNM effects with a feature opposite to the expected suppression because of the final-state parton energy loss effect in the QGP. The difference of EPS, EKS, HKN and DS parametrization sets of nuclear parton distribution functions is appreciable for dijet invariant mass spectra and transverse momentum spectra at p+Pb collisions, and becomes more pronounced for those at Pb+Pb reactions.Comment: 10 pages, 11 figure

An Extreme Solar Event of 20 January 2005: Properties of the Flare and the Origin of Energetic Particles

The extreme solar and SEP event of 20 January 2005 is analyzed from two perspectives. Firstly, we study features of the main phase of the flare, when the strongest emissions from microwaves up to 200 MeV gamma-rays were observed. Secondly, we relate our results to a long-standing controversy on the origin of SEPs arriving at Earth, i.e., acceleration in flares, or shocks ahead of CMEs. All emissions from microwaves up to 2.22 MeV line gamma-rays during the main flare phase originated within a compact structure located just above sunspot umbrae. A huge radio burst with a frequency maximum at 30 GHz was observed, indicating the presence of a large number of energetic electrons in strong magnetic fields. Thus, protons and electrons responsible for flare emissions during its main phase were accelerated within the magnetic field of the active region. The leading, impulsive parts of the GLE, and highest-energy gamma-rays identified with pi^0-decay emission, are similar and correspond in time. The origin of the pi^0-decay gamma-rays is argued to be the same as that of lower energy emissions. We estimate the sky-plane speed of the CME to be 2000-2600 km/s, i.e., high, but of the same order as preceding non-GLE-related CMEs from the same active region. Hence, the flare itself rather than the CME appears to determine the extreme nature of this event. We conclude that the acceleration, at least, to sub-relativistic energies, of electrons and protons, responsible for both the flare emissions and the leading spike of SEP/GLE by 07 UT, are likely to have occurred simultaneously within the flare region. We do not rule out a probable contribution from particles accelerated in the CME-driven shock for the leading GLE spike, which seemed to dominate later on.Comment: 34 pages, 14 Postscript figures. Solar Physics, accepted. A typo corrected. The original publication is available at http://www.springerlink.co

Origins of the Ambient Solar Wind: Implications for Space Weather

The Sun's outer atmosphere is heated to temperatures of millions of degrees, and solar plasma flows out into interplanetary space at supersonic speeds. This paper reviews our current understanding of these interrelated problems: coronal heating and the acceleration of the ambient solar wind. We also discuss where the community stands in its ability to forecast how variations in the solar wind (i.e., fast and slow wind streams) impact the Earth. Although the last few decades have seen significant progress in observations and modeling, we still do not have a complete understanding of the relevant physical processes, nor do we have a quantitatively precise census of which coronal structures contribute to specific types of solar wind. Fast streams are known to be connected to the central regions of large coronal holes. Slow streams, however, appear to come from a wide range of sources, including streamers, pseudostreamers, coronal loops, active regions, and coronal hole boundaries. Complicating our understanding even more is the fact that processes such as turbulence, stream-stream interactions, and Coulomb collisions can make it difficult to unambiguously map a parcel measured at 1 AU back down to its coronal source. We also review recent progress -- in theoretical modeling, observational data analysis, and forecasting techniques that sit at the interface between data and theory -- that gives us hope that the above problems are indeed solvable.Comment: Accepted for publication in Space Science Reviews. Special issue connected with a 2016 ISSI workshop on "The Scientific Foundations of Space Weather." 44 pages, 9 figure

The cost-effectiveness of providing antenatal lifestyle advice for women who are overweight or obese: the LIMIT randomised trial

BACKGROUND: Overweight and obesity during pregnancy is common, although robust evidence about the economic implications of providing an antenatal dietary and lifestyle intervention for women who are overweight or obese is lacking. We conducted a health economic evaluation in parallel with the LIMIT randomised trial. Women with a singleton pregnancy, between 10(+0)-20(+0) weeks, and BMI ≥25 kg/m(2) were randomised to Lifestyle Advice (a comprehensive antenatal dietary and lifestyle intervention) or Standard Care. The economic evaluation took the perspective of the health care system and its patients, and compared costs encountered from the additional use of resources from time of randomisation until six weeks postpartum. Increments in health outcomes for both the woman and infant were considered in the cost-effectiveness analysis. Mean costs and effects in the treatment groups allocated at randomisation were compared, and incremental cost effectiveness ratios (ICERs) and confidence intervals (95%) calculated. Bootstrapping was used to confirm the estimated confidence intervals, and to generate acceptability curves representing the probability of the intervention being cost-effective at alternative monetary equivalent values for the outcomes avoiding high infant birth weight, and respiratory distress syndrome. Analyses utilised intention to treat principles. RESULTS: Overall, the increase in mean costs associated with providing the intervention was offset by savings associated with improved immediate neonatal outcomes, rendering the intervention cost neutral (Lifestyle Advice Group $11261.19±$14573.97 versus Standard Care Group $11306.70±$14562.02; p=0.094). Using a monetary value of $20,000 as a threshold value for avoiding an additional infant with birth weight above 4 kg, the probability that the antenatal intervention is cost-effective is 0.85, which increases to 0.95 when the threshold monetary value increases to$45,000. CONCLUSIONS: Providing an antenatal dietary and lifestyle intervention for pregnant women who are overweight or obese is not associated with increased costs or cost savings, but is associated with a high probability of cost effectiveness. Ongoing participant follow-up into childhood is required to determine the medium to long-term impact of the observed, short-term endpoints, to more accurately estimate the value of the intervention on risk of obesity, and associated costs and health outcomes. TRIALS REGISTRATION: Australian and New Zealand Clinical Trials Registry (ACTRN12607000161426).Jodie M Dodd, Sharmina Ahmed, Jonathan Karnon, Wendy Umberger, Andrea R Deussen, Thach Tran, Rosalie M Grivell, Caroline A Crowther, Deborah Turnbull, Andrew J McPhee, Gary Wittert, Julie A Owens, Jeffrey S Robinson and For the LIMIT Randomised Trial Grou