Abstract
Recent determination of the Hubble constant via Cepheid-calibrated supernovae by Riess et al.find ∼3σ tension with inferences based on cosmic microwave background (CMB) temperature and ...polarization measurements from Planck. This tension could be an indication of inadequacies in the concordance Λcold dark matter model. Here, we investigate the possibility that the discrepancy could instead be due to systematic bias or uncertainty in the Cepheid calibration step of the distance ladder measurement by Riess et al. We consider variations in total-to-selective extinction of Cepheid flux as a function of line of sight, hidden structure in the period–luminosity relationship, and potentially different intrinsic colour distributions of Cepheids as a function of host galaxy. Considering all potential sources of error, our final determination of H0 = 73.3 ± 1.7 km s−1Mpc−1 (not including systematic errors from the treatment of geometric distances or Type Ia supernovae) shows remarkable robustness and agreement with Riess et al. We conclude systematics from the modelling of Cepheid photometry, including Cepheid selection criteria, cannot explain the observed tension between Cepheid-variable and CMB-based inferences of the Hubble constant. Considering a ‘model-independent’ approach to relating Cepheids in galaxies with known distances to Cepheids in galaxies hosting a Type Ia supernova and finding agreement with the Riess et al. result, we conclude no generalization of the model relating anchor and host Cepheid magnitude measurements can introduce significant bias in the H0 inference.
Tuning goodness-of-fit tests Arrasmith, A; Follin, B; Anderes, E ...
Monthly notices of the Royal Astronomical Society,
04/2019, Letnik:
484, Številka:
2
Journal Article
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As modern precision cosmological measurements continue to show agreement with the broad features of the standard Λ cold dark matter (ΛCDM) cosmological model, we are increasingly motivated to look ...for small departures from the standard model’s predictions that might not be detected with standard approaches. While searches for extensions and modifications of ΛCDM have to date turned up no convincing evidence of beyond-the-standard-model cosmology, the list of models compared against ΛCDM is by no means complete and is often governed by readily coded modifications to standard Boltzmann codes. Also, standard goodness-of-fit methods such as a naive χ2 test fail to put strong pressure on the null hypothesis, since modern data sets have orders of magnitudes more degrees of freedom than the null hypothesis. Here we present a method of tuning goodness-of-fit tests to detect potential subdominant extra-ΛCDM signals present in the data through compressing observations in a way that maximizes extra-ΛCDM signal variation over noise and ΛCDM variation. This method, based on a Karhunen–Loève transformation of the data, is tuned to be maximally sensitive to particular types of variations characteristic of the tuning model, but unlike direct model comparison, the test is also sensitive to features that only partially mimic the tuning model. As an example of its use, we apply this method in the context of a non-standard primordial spectrum compared against the 2015 Planck cosmic microwave background temperature power spectrum. We find no evidence for extra-ΛCDM physics.
We present a measurement of the cosmic microwave background (CMB) temperature power spectrum using data from the recently completed South Pole Telescope Sunyaev-Zel'dovich (SPT-SZ) survey. We report ...CMB temperature anisotropy power over the multipole range 650 < l < 3000. We fit the SPT bandpowers, combined with the 7 yr Wilkinson Microwave Anisotropy Probe (WMAP7) data, with a six-parameter ACDM cosmological model and find that the two datasets are consistent and well fit by the model. Adding SPT measurements significantly improves ACDM parameter constraints; in particular, the constraint on theta sub(s) tightens by a factor of 2.7. The impact of gravitational lensing is detected at 8.1sigma, the most significant detection to date. These new constraints on n sub(s) and r have significant implications for our understanding of inflation, which we discuss in the context of selected single-field inflation models.
We study the consistency of 150 GHz data from the South Pole Telescope (SPT) and 143 GHz data from the Planck satellite over the patch of sky covered by the SPT-SZ survey. We first visually compare ...the maps and find that the residuals appear consistent with noise after accounting for differences in angular resolution and filtering. We then calculate (1) the cross-spectrum between two independent halves of SPT data, (2) the cross-spectrum between two independent halves of Planck data, and (3) the cross-spectrum between SPT and Planck data. We find that the three cross-spectra are well fit (PTE = 0.30) by the null hypothesis in which both experiments have measured the same sky map up to a single free calibration parameter-i.e., we find no evidence for systematic errors in either data set. As a by-product, we improve the precision of the SPT calibration by nearly an order of magnitude, from 2.6% to 0.3% in power. Finally, we compare all three cross-spectra to the full-sky Planck power spectrum and find marginal evidence for differences between the power spectra from the SPT-SZ footprint and the full sky. We model these differences as a power law in spherical harmonic multipole number. The best-fit value of this tilt is consistent among the three cross-spectra in the SPT-SZ footprint, implying that the source of this tilt is a sample variance fluctuation in the SPT-SZ region relative to the full sky. The consistency of cosmological parameters derived from these data sets is discussed in a companion paper.
Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): This work was supported by the European Union’s Horizon 2020 research and innovation program (ERC ...Advanced Grant) and the Novo Nordisk Foundation. Background Doxorubicin is a common and highly effective chemotherapeutic. However, its use is limited by cardiotoxic side effects, which occur in 5-23 % of patients treated, and the lack of methods to detect these conditions at early time points. Purpose In the present study, we evaluated if 64CuCu-RGD positron emission tomography/computed tomography (PET/CT) could detect cardiotoxicity in a rat model of doxorubicin induced heart failure. Methods Male Lewis rats were divided into two groups and treated with either a cumulative dose of 15 mg/kg doxorubicin (n = 15) or left untreated (n = 10). Cardiac anatomy and function were assessed using magnetic resonance imaging at baseline and in week eight. 64CuCu-RGD PET/CT scans were performed in week four. All animal experiments were approved by the Danish Animal Experiments Inspectorate (authorization number 2016-15-0201-00920) and study performed in accordance with the ARRIVA guidelines. Results Doxorubicin treatment led to a decline in left ventricular ejection fraction (66.5 ± 0.85 % to 46.67 ± 0.84 %, p < 0.001), as well as an increase in septal and thymic uptake of 64CuCu-RGD (0.46 ± 0.02 vs. 0.29 ± 0.04, <0.001 and 0.87 ± 0.03 vs. 0.40 ± 0.07, p < 0.001, respectively). In addition, doxorubicin altered the cardiac gene expression, led to infiltration of macrophages (0.90 ± 0.12 % vs. 0.30 ± 0.04 %, p <0.001), reduced endothelial content (0.19 ± 0.02 % vs. 0.47 ± 0.07 %, p < 0.001), and increased interstitial fibrosis (13.6 ± 0.86 % vs. 10.5 ± 0.66 %, p = 0.014). Furthermore, concentrations of inflammatory plasma proteins were increased in the doxorubicin group. Conclusion Doxorubicin treatment resulted in the development of cardiotoxicity and heart failure, which could be detected using 64CuCu-RGD PET/CT at early time points. 64CuCu-RGD uptake in the myocardial septum and thymus predicted low left ventricular ejection fraction in week eight, thus it may serve as an early marker of cardiotoxicity.Experimental setup and timeline
Abstract
Introduction
Atherosclerosis is one of the most common inflammatory disorders leading to cardiovascular disease. Incretin therapies such as Glucagon like peptide 1 (GLP-1) receptor agonists ...has demonstrated efficacy in reducing major adverse cardiovascular events among high risk populations, possibly due to a reduction in vascular inflammation. Positron emission tomography (PET) is a promising modality in the study of atherosclerosis since it has the ability to evaluate physiological processes in vivo. The somatostaton receptor 2 (SSTR2) targeting tracer 64CuCu-DOTA-TATE (DOTATATE) has high specificity for activated macrophages, which are one on the key instigators of atherosclerosis. Two other radiotracers, more commonly used to study atherosclerosis are Na18FF (NaF) a radiotracer used for detection of vascular microcalcifications, and 18FFDG (FDG) used for visualization of inflammatory metabolic activity.
Purpose
The purpose of this study was to evaluate the anti-atherosclerotic and anti-inflammatory effects of the GLP-1 receptor agonist Semaglutide, using molecular imaging with DOTATATE, NaF and FDG, in a rabbit model of advanced atherosclerosis.
Methods
A total of 23 female New Zealand White rabbits were fed a high cholesterol diet for 4 months and endothelial denudation of the aorta was performed twice (Fig 1A). The animals underwent baseline PET/CT scans using DOTATATE and FDG. They were then randomly allocated to an intervention group (n=12) or control group (n=11) receiving bi- weekly subcutaneous injections of either Semaglutide in a dose escalating regimen up to 44 μg/kg/week, or placebo (n=11). The intervention period was 16 weeks for both groups. At follow-up, the animals underwent PET/CT scans with DOTATATE, FDG and NaF. Regions of interest were drawn on all CT scans of the aorta from the right renal artery to the iliac bifurcation, and SUVmax was measured from the superimposed PET scans. Data are presented as means ± SEM.
Results
SUVmax for FDG and DOTATATE were similar in the 2 groups at baseline (DOTATATE: 7.59±0.48 vs 6.69±0.28, P=0.13 and FDG: 2.63±0.12 vs 2.86±0.19 P=0.29). At follow-up, the Semaglutide group had a significantly lower uptake of both DOTATATE and FDG, although the largest difference was observed for DOTATATE (DOTATATE: 5.83±0.24 vs 7.10±0.33, P=0.001 and FDG: 2.49±0.13 vs 2.99±0.15, P=0.034) (Fig 1BC). Microcalcifications visualized using NaF PET, showed no difference at follow-up between the Semaglutide and the control group (4.15±0.30 vs 3.92±0.34, P=0.62) (Fig 1D). Increase in body weight was significantly attenuated in the Semaglutide group compared to the control group at follow-up (0.25±3.29% vs 10.68±3.01%, P=0.0016).
Conclusions
Semaglutide decreases vascular uptake of the SSTR2 tracer, DOTATATE, and FDG but not NaF. This supports the hypothesis that Semaglutide reduces inflammation by means of decreased macrophage activity and metabolism in the arterial wall.
Figure 1
Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark
We explore extensions to the ΛCDM cosmology using measurements of the cosmic microwave background (CMB) from the recent SPT-SZ survey, along with data from WMAP7 and measurements of H {sub 0} and ...baryon acoustic oscillation (BAO). We check for consistency within ΛCDM between these data sets, and find some tension. The CMB alone gives weak support to physics beyond ΛCDM, due to a slight trend relative to ΛCDM of decreasing power toward smaller angular scales. While it may be due to statistical fluctuation, this trend could also be explained by several extensions. We consider running of the primordial spectral index (dn{sub s} /dln k), as well as two extensions that modify the damping tail power (the primordial helium abundance Y{sub p} and the effective number of neutrino species N {sub eff}) and one that modifies the large-scale power due to the integrated Sachs-Wolfe effect (the sum of neutrino masses ∑m {sub ν}). These extensions have similar observational consequences and are partially degenerate when considered simultaneously. Of the six one-parameter extensions considered, we find CMB to have the largest preference for dn{sub s} /dln k with –0.046 < dn{sub s} /dln k < –0.003 at 95% confidence, which strengthens to a 2.7σ indication of dn{sub s} /dln k < 0 from CMB+BAO+H {sub 0}. Detectable dn{sub s} /dln k ≠ 0 is difficult to explain in the context of single-field, slow-roll inflation models. We find N {sub eff} = 3.62 ± 0.48 for the CMB, which tightens to N {sub eff} = 3.71 ± 0.35 from CMB+BAO+H {sub 0}. Larger values of N {sub eff} relieve the mild tension between CMB, BAO, and H {sub 0}. When the Sunyaev-Zel'dovich selected galaxy cluster abundances (SPT{sub CL}) data are also included, we obtain N {sub eff} = 3.29 ± 0.31. Allowing for ∑m {sub ν} gives a 3.0σ detection of ∑m {sub ν} > 0 from CMB+BAO+H {sub 0} +SPT{sub CL}. The median value is (0.32 ± 0.11) eV, a factor of six above the lower bound set by neutrino oscillation observations. All data sets except H {sub 0} show some preference for massive neutrinos; data combinations including H {sub 0} favor nonzero masses only if BAO data are also included. We also constrain the two-parameter extensions N {sub eff} + ∑m {sub ν} and N {sub eff} + Y{sub p} to explore constraints on additional light species and big bang nucleosynthesis, respectively.
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