Feedback Control of the National Airspace System

This paper proposes a general modeling framework adapted to the feedback control of traffic flows in Eulerian models of the National Airspace System. It is shown that the problems of scheduling and routing aircraft flows in the National Airspace System can be posed as the control of a network of queues with load-dependent service rates. Focus can then shift to developing techniques to ensure that the aircraft queues in each airspace sector, which are an indicator of the air traffic controller workloads, are kept small. This paper uses the proposed framework to develop control laws that help prepare the National Airspace System for fast recovery from a weather event, given a probabilistic forecast of capacities. In particular, the model includes the management of airport arrivals and departures subject to runway capacity constraints, which are highly sensitive to weather disruptions.National Science Foundation (U.S.) (Contract ECCS-0745237)United States. National Aeronautics and Space Administration (Contract NNA06CN24A

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

First light of the VLT planet finder SPHERE IV : Physical and chemical properties of the planets around HR8799

This is a pre-copyedited, author produced PDF of an article accepted for publication in Astronomy & Astrophysics following peer review. Subject to 12 month's embargo period. Embargo end date: 16 February 2017. The version of record [Bonnefoy, M., 'First light of the VLT planet finder SPHERE, IV. Physical and chemical properties of the planets around HR8799', A&A, 587, A58 (2016), first published online 16 February 2016] is available online at doi http://dx.doi.org/10.1051/0004-6361/201526906Context. The system of four planets discovered around the intermediate-mass star HR8799 offers a unique opportunity to test planet formation theories at large orbital radii and to probe the physics and chemistry at play in the atmospheres of self-luminous young (∼30 Myr) planets. We recently obtained new photometry of the four planets and low-resolution (R∼30) spectra of HR8799 d and e with the SPHERE instrument (paper III). Aims. In this paper (paper IV), we aim to use these spectra and available photometry to determine how they compare to known objects, what the planet physical properties are, and how their atmospheres work. Methods. We compare the available spectra, photometry, and spectral-energy distribution (SED) of the planets to field dwarfs and young companions. In addition, we use the extinction from corundum, silicate (enstatite and forsterite), or iron grains likely to form in the atmosphere of the planets to try to better understand empirically the peculiarity of their spectrophotometric properties. To conclude, we use three sets of atmospheric models (BT-SETTL14, Cloud-AE60, Exo-REM) to determine which ingredients are critically needed in the models to represent the SED of the objects, and to constrain their atmospheric parameters (T eff , log g, M/H). Results. We find that HR8799d and e properties are well reproduced by those of L6-L8 dusty dwarfs discovered in the field, among which some are candidate members of young nearby associations. No known object reproduces well the properties of planets b and c. Nevertheless, we find that the spectra and WISE photometry of peculiar and/or young early-T dwarfs reddened by submicron grains made of corundum, iron, enstatite, or forsterite successfully reproduce the SED of these planets. Our analysis confirms that only the Exo-REM models with thick clouds fit (within 2σ) the whole set of spectrophotometric datapoints available for HR8799 d and e for T eff = 1200 K, log g in the range 3.0-4.5, and M/H=+0.5. The models still fail to reproduce the SED of HR8799c and b. The determination of the metallicity, log g, and cloud thickness are degenerate. Conclusions. Our empirical analysis and atmospheric modelling show that an enhanced content in dust and decreased CIA of H2 is certainly responsible for the deviation of the properties of the planet with respect to field dwarfs. The analysis suggests in addition that HR8799c and b have later spectral types than the two other planets, and therefore could both have lower masses.Peer reviewe