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- Tinetti, Giovanna, et al.
(author)
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The EChO science case
- 2015
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In: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 40:2-3, s. 329-391
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Journal article (peer-reviewed)abstract
- The discovery of almost two thousand exoplanets has revealed an unexpectedly diverse planet population. We see gas giants in few-day orbits, whole multi-planet systems within the orbit of Mercury, and new populations of planets with masses between that of the Earth and Neptune-all unknown in the Solar System. Observations to date have shown that our Solar System is certainly not representative of the general population of planets in our Milky Way. The key science questions that urgently need addressing are therefore: What are exoplanets made of? Why are planets as they are? How do planetary systems work and what causes the exceptional diversity observed as compared to the Solar System? The EChO (Exoplanet Characterisation Observatory) space mission was conceived to take up the challenge to explain this diversity in terms of formation, evolution, internal structure and planet and atmospheric composition. This requires in-depth spectroscopic knowledge of the atmospheres of a large and well-defined planet sample for which precise physical, chemical and dynamical information can be obtained. In order to fulfil this ambitious scientific program, EChO was designed as a dedicated survey mission for transit and eclipse spectroscopy capable of observing a large, diverse and well-defined planet sample within its 4-year mission lifetime. The transit and eclipse spectroscopy method, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allows us to measure atmospheric signals from the planet at levels of at least 10(-4) relative to the star. This can only be achieved in conjunction with a carefully designed stable payload and satellite platform. It is also necessary to provide broad instantaneous wavelength coverage to detect as many molecular species as possible, to probe the thermal structure of the planetary atmospheres and to correct for the contaminating effects of the stellar photosphere. This requires wavelength coverage of at least 0.55 to 11 mu m with a goal of covering from 0.4 to 16 mu m. Only modest spectral resolving power is needed, with R similar to 300 for wavelengths less than 5 mu m and R similar to 30 for wavelengths greater than this. The transit spectroscopy technique means that no spatial resolution is required. A telescope collecting area of about 1 m(2) is sufficiently large to achieve the necessary spectro-photometric precision: for the Phase A study a 1.13 m(2) telescope, diffraction limited at 3 mu m has been adopted. Placing the satellite at L2 provides a cold and stable thermal environment as well as a large field of regard to allow efficient time-critical observation of targets randomly distributed over the sky. EChO has been conceived to achieve a single goal: exoplanet spectroscopy. The spectral coverage and signal-to-noise to be achieved by EChO, thanks to its high stability and dedicated design, would be a game changer by allowing atmospheric composition to be measured with unparalleled exactness: at least a factor 10 more precise and a factor 10 to 1000 more accurate than current observations. This would enable the detection of molecular abundances three orders of magnitude lower than currently possible and a fourfold increase from the handful of molecules detected to date. Combining these data with estimates of planetary bulk compositions from accurate measurements of their radii and masses would allow degeneracies associated with planetary interior modelling to be broken, giving unique insight into the interior structure and elemental abundances of these alien worlds. EChO would allow scientists to study exoplanets both as a population and as individuals. The mission can target super-Earths, Neptune-like, and Jupiter-like planets, in the very hot to temperate zones (planet temperatures of 300-3000 K) of F to M-type host stars. The EChO core science would be delivered by a three-tier survey. The EChO Chemical Census: This is a broad survey of a few-hundred exoplanets, which allows us to explore the spectroscopic and chemical diversity of the exoplanet population as a whole. The EChO Origin: This is a deep survey of a subsample of tens of exoplanets for which significantly higher signal to noise and spectral resolution spectra can be obtained to explain the origin of the exoplanet diversity (such as formation mechanisms, chemical processes, atmospheric escape). The EChO Rosetta Stones: This is an ultra-high accuracy survey targeting a subsample of select exoplanets. These will be the bright "benchmark" cases for which a large number of measurements would be taken to explore temporal variations, and to obtain two and three dimensional spatial information on the atmospheric conditions through eclipse-mapping techniques. If EChO were launched today, the exoplanets currently observed are sufficient to provide a large and diverse sample. The Chemical Census survey would consist of > 160 exoplanets with a range of planetary sizes, temperatures, orbital parameters and stellar host properties. Additionally, over the next 10 years, several new ground- and space-based transit photometric surveys and missions will come on-line (e.g. NGTS, CHEOPS, TESS, PLATO), which will specifically focus on finding bright, nearby systems. The current rapid rate of discovery would allow the target list to be further optimised in the years prior to EChO's launch and enable the atmospheric characterisation of hundreds of planets.
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- Pantazis, N, et al.
(author)
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Determining the likely place of HIV acquisition for migrants in Europe combining subject-specific information and biomarkers data
- 2019
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In: Statistical methods in medical research. - : SAGE Publications. - 1477-0334 .- 0962-2802. ; 28:7, s. 1979-1997
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Journal article (peer-reviewed)abstract
- In most HIV-positive individuals, infection time is only known to lie between the time an individual started being at risk for HIV and diagnosis time. However, a more accurate estimate of infection time is very important in certain cases. For example, one of the objectives of the Advancing Migrant Access to Health Services in Europe (aMASE) study was to determine if HIV-positive migrants, diagnosed in Europe, were infected pre- or post-migration. We propose a method to derive subject-specific estimates of unknown infection times using information from HIV biomarkers’ measurements, demographic, clinical, and behavioral data. We assume that CD4 cell count (CD4) and HIV-RNA viral load trends after HIV infection follow a bivariate linear mixed model. Using post-diagnosis CD4 and viral load measurements and applying the Bayes’ rule, we derived the posterior distribution of the HIV infection time, whereas the prior distribution was informed by AIDS status at diagnosis and behavioral data. Parameters of the CD4–viral load and time-to-AIDS models were estimated using data from a large study of individuals with known HIV infection times (CASCADE). Simulations showed substantial predictive ability (e.g. 84% of the infections were correctly classified as pre- or post-migration). Application to the aMASE study ( n = 2009) showed that 47% of African migrants and 67% to 72% of migrants from other regions were most likely infected post-migration. Applying a Bayesian method based on bivariate modeling of CD4 and viral load, and subject-specific information, we found that the majority of HIV-positive migrants in aMASE were most likely infected after their migration to Europe.
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- Schaap, M., et al.
(author)
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Standardized evaluation methodology and reference database for evaluating coronary artery centerline extraction algorithms
- 2009
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In: Medical Image Analysis. - : Elsevier. - 1361-8415 .- 1361-8423. ; 13:5, s. 701-714
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Journal article (peer-reviewed)abstract
- Efficiently obtaining a reliable coronary artery centerline from computed tomography angiography data is relevant in clinical practice. Whereas numerous methods have been presented for this purpose, up to now no standardized evaluation methodology has been published to reliably evaluate and compare the performance of the existing or newly developed coronary artery centerline extraction algorithms. This paper describes a standardized evaluation methodology and reference database for the quantitative evaluation of coronary artery centerline extraction algorithms. The contribution of this work is fourfold: (1) a method is described to create a consensus centerline with multiple observers, (2) well-defined measures are presented for the evaluation of coronary artery centerline extraction algorithms, (3) a database containing 32 cardiac CTA datasets with corresponding reference standard is described and made available, and (4) 13 coronary artery centerline extraction algorithms, implemented by different research groups, are quantitatively evaluated and compared. The presented evaluation framework is made available to the medical imaging community for benchmarking existing or newly developed coronary centerline extraction algorithms.
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- Faulx, M. D., et al.
(author)
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Obstructive sleep apnea and its management in patients with atrial fibrillation: An International Collaboration of Sleep Apnea Cardiovascular Trialists (INCOSACT) global survey of practicing cardiologists
- 2022
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In: International journal of cardiology: Heart and Vasculature (IJCHA). - : Elsevier BV. - 2352-9067. ; 42
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Journal article (peer-reviewed)abstract
- Background: Among international cardiologists it is unclear whether equipoise exists regarding the benefit of diagnosing and managing obstructive sleep apnea (OSA) to improve atrial fibrillation (AF) outcomes and whether clinical practice and equipoise are linked. Methods: Between January 2019 and June 2020 we distributed a web-based 12-question survey regarding OSA and AF management to practicing cardiologists in 16 countries. Results: The United States, Japan, Sweden, and Turkey accounted for two-thirds of responses. 863 cardiologists responded; half were general cardiologists, a quarter electrophysiologists. Responses regarding treating OSA with CPAP to improve AF endpoints were mixed. 33% of respondents referred AF patients for OSA screening. OSA was diagnosed in 48% of referred patients and continuous positive airway pressure (CPAP) was prescribed for 59% of them. Nearly 70% of respondents believed randomized controlled trials (RCTs) of OSA treatment in AF patients were necessary and indicated willingness to contribute to such trials. Conclusions: There was no clinical equipoise among surveyed cardiologists; a majority expressed certainty that combined OSA and AF treatment is superior to AF treatment alone for improving AF outcomes. However, a minority of surveyed cardiologists referred AF patients for OSA testing, and while half of screened AF patients had OSA, CPAP was prescribed in little more than half of them, reflecting the view that better clinical trial evidence is needed to support this practice. Our results underscore the need for larger, multi-national prospective studies of OSA treatment and AF outcomes to inform more uniform society guideline recommendations.
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- Chen, B. X., et al.
(author)
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Effect of Continuous Positive Airway Pressure on Weight and Local Adiposity in Adults with Obstructive Sleep Apnea A Meta-Analysis
- 2021
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In: Annals of the American Thoracic Society. - 1546-3222 .- 2329-6933. ; 18:10, s. 1717-1727
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Journal article (peer-reviewed)abstract
- Rationale: Evidence suggests that continuous positive airway pressure (CPAP) treatment promotes weight gain in patients with obstructive sleep apnea (OSA). It is unclear whether weight gain is influenced by CPAP adherence or comorbid disorders. Objectives: To examine the CPAP effects on body mass index (BMI) and local adiposity and the potential moderators of CPAP effects on BMI in patients with OSA. Methods: We searched PubMed/Medline, Embase, and Cochrane through December 2019. Randomized controlled trials of CPAP versus control treatment with >4 weeks' treatment were included. Results: A total of 39 randomized controlled trials with 6,954 subjects were included. In intention-to-treat analysis, the BMI increased significantly after CPAP treatment compared with control treatment (weighted mean difference [WMD], 0.148 kg/m(2); 95% confidence interval, 0.04-0.26; P = 0.001). In studies demonstrating an increase in the BMI, waist and neck circumferences were also significantly increased. Subgroup analyses revealed that an increased BMI was attributable to CPAP use of <5 h/night (WMD, 0.231) but was not attributable to CPAP use of.5 h/night (WMD, 0.001; between-group P value = 0.049). Furthermore, the BMI increased significantly in patients without cardiovascular disease (CVD; WMD, 0.200), whereas it decreased significantly in those with CVD at baseline (WMD, 20.188; between-group P value, 0.001). Moreover, the BMI increased significantly in patients with dysglycemia (WMD, 0.499) but did not increase in those without dysglycemia at baseline (WMD, 0.100; between-group P value = 0.032). Meta-regression confirmed the subgroup findings. Conclusions: The BMI increased significantly in patients with OSA after CPAP treatment, especially in those with CPAP use of <5 h/night, without CVD and/or with dysglycemia at baseline. CPAP use of at least 5 h/night seems to be necessary in mitigating the risk for weight gain in patients with OSA.
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- Prusakov, Pavel, et al.
(author)
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A global point prevalence survey of antimicrobial use in neonatal intensive care units : The no-more-antibiotics and resistance (NO-MAS-R) study
- 2021
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In: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 32
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Journal article (peer-reviewed)abstract
- Background: Global assessment of antimicrobial agents prescribed to infants in the neonatal intensive care unit (NICU) may inform antimicrobial stewardship efforts.Methods: We conducted a one-day global point prevalence study of all antimicrobials provided to NICU infants. Demographic, clinical, and microbiologic data were obtained including NICU level, census, birth weight, gestational/chronologic age, diagnoses, antimicrobial therapy (reason for use; length of therapy), antimicrobial stewardship program (ASP), and 30-day in-hospital mortality.Findings: On July 1, 2019, 26% of infants (580/2,265; range, 0-100%; median gestational age, 33 weeks; median birth weight, 1800 g) in 84 NICUs (51, high-income; 33, low-to-middle income) from 29 countries (14, high-income; 15, low-to-middle income) in five continents received >= 1 antimicrobial agent (92%, antibacterial; 19%, antifungal; 4%, antiviral). The most common reasons for antibiotic therapy were "rule-out" sepsis (32%) and "culture-negative" sepsis (16%) with ampicillin (40%), gentamicin (35%), amikacin (19%), vancomycin (15%), and meropenem (9%) used most frequently. For definitive treatment of presumed/confirmed infection, vancomycin (26%), amikacin (20%), and meropenem (16%) were the most prescribed agents. Length of therapy for culture-positive and "culture-negative" infections was 12 days (median; IQR, 8-14) and 7 days (median; IQR, 5-10), respectively. Mortality was 6% (42%, infection-related). An NICU ASP was associated with lower rate of antibiotic utilization (p = 0.02).Interpretation: Global NICU antibiotic use was frequent and prolonged regardless of culture results. NICU-specific ASPs were associated with lower antibiotic utilization rates, suggesting the need for their implementation worldwide.
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- Rodriguez-Garcia, A., et al.
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Insertion of exogenous epitopes in the E3-19K of oncolytic adenoviruses to enhance TAP-independent presentation and immunogenicity
- 2015
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In: Gene Therapy. - : Springer Science and Business Media LLC. - 0969-7128 .- 1476-5462. ; 22:7, s. 596-601
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Journal article (peer-reviewed)abstract
- Oncolytic adenoviruses can promote immune responses against tumors by expressing and/or displaying tumor-associated antigens. However, the strong immunodominance of viral antigens mask responses against tumor epitopes. In addition, defects in major histocompatibility complex class I antigen presentation pathway such as the downregulation of the transporter-associated with antigen processing (TAP) are frequently associated with immune evasion of tumor cells. To promote the immunogenicity of exogenous epitopes in the context of an oncolytic adenovirus, we have taken advantage of the ER localization of the viral protein E3-19K. We have inserted tumor-associated epitopes after the N-terminal signal sequence for membrane insertion of this protein and flanked them with linkers cleavable by the protease furin to facilitate their TAP-independent presentation. This strategy allowed an enhanced presentation of the exogenous epitopes in TAP-deficient tumor cells in vitro and the generation of higher specific immune responses in vivo that were able to significantly control tumor growth.
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- Theorell-Haglöw, Jenny, et al.
(author)
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Changes of vitamin D levels and bone turnover markers after CPAP therapy : a randomized sham-controlled trial
- 2018
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In: Journal of Sleep Research. - : WILEY. - 0962-1105 .- 1365-2869. ; 27:4
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Journal article (peer-reviewed)abstract
- The aim was to investigate whether continuous positive airway pressure treatment could modulate serum vitamin D (25-hydroxyvitamin D) and bone turnover markers (collagen-type 1 cross-linked C-telopeptide, osteocalcin and N-terminal propeptide of type 1 collagen) in secondary analysis from a randomized controlled trial. Sixty-five continuous positive airway pressure-naive male patients with obstructive sleep apnea (age=49 +/- 12years, apnea-hypopnea index=39.9 +/- 17.7events h(-1), body mass index=31.3 +/- 5.2kgm(-2)) were randomized to receive either real (n=34) or sham (n=31) continuous positive airway pressure for 12weeks. At 12weeks, all participants received real continuous positive airway pressure for an additional 12weeks. After 12weeks of continuous positive airway pressure (real versus sham), there were nobetween-group differences for any of the main outcomes [25-hydroxyvitamin D: -0.80 +/- 5.28ngmL(-1) (mean +/- SE) versus 3.08 +/- 3.66ngmL(-1), P=0.42; collagen-type 1 cross-linked C-telopeptide: 0.011 +/- 0.014ngmL(-1) versus -0.004 +/- 0.009ngmL(-1), P=0.48; osteocalcin: 1.13 +/- 1.12ngmL(-1) versus 0.46 +/- 0.75ng mL(-1), P=0.80; N-terminal propeptide of type 1 collagen: 2.07 +/- 3.05gL(-1) versus -1.05 +/- 2.13gL(-1), P=0.48]. There were no further differences in subgroup analyses (continuous positive airway pressure-compliant patients, patients with severe obstructive sleep apnea or sleepy patients). However, after 24weeks irrespective of initial randomization, vitamin D increased in patients with severe obstructive sleep apnea (9.56 +/- 5.51ngmL(-1), P=0.045) and in sleepy patients (14.0 +/- 4.69ngmL(-1), P=0.007). Also, there was a significant increase in osteocalcin at 24weeks (3.27 +/- 1.06ngmL(-1), P=0.01) in compliant patients. We conclude that 12weeks of continuous positive airway pressure did not modulate vitamin D or modulate any of the bone turnover markers compared with sham. However, it is plausible that continuous positive airway pressure may have late beneficial effects on vitamin D levels and bone turnover markers in selected groups of patients with obstructive sleep apnea.
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