•Immune checkpoint inhibitors (ICIs) have shifted the therapeutic approach to NSCLC•Reproducible biomarkers of ICI benefit represent an unmet and urgent need•Circulating descriptors of cancer-host ...immune interaction were explored here•sPD-L1, CD8+PD-1+ and NK cells enclosed a highly prognostic immune effector score•Blood-based multiparametric models might non-invasively predict ICI response
Upfront criteria to foresee immune checkpoint inhibitors (ICIs) efficacy are far from being identified. Thus, we integrated blood descriptors of pro-inflammatory/immunosuppressive or effective anti-tumor response to non-invasively define predictive immune profiles in ICI-treated advanced non-small cell lung cancer (NSCLC).
Peripheral blood (PB) was prospectively collected at baseline from 109 consecutive NSCLC patients undergoing ICIs as first or more line treatment. Soluble PD-L1 (sPD-L1) (immunoassay), CD8+PD-1+ and NK (FACS) cells were assessed and interlaced to generate an Immune effector Score (IeffS). Lung Immune Prognostic Index (LIPI) was computed by LDH levels and derived Neutrophil-to-Lymphocyte Ratio (dNLR). All these parameters were correlated with survival outcome and treatment response.
High sPD-L1 and low CD8+PD-1+ and NK number had negative impact on PFS (P < 0.001), OS (P < 0.01) and ICI-response (P < 0.05). Thus, sPD-L1high, CD8+PD-1+low and NKlow were considered as risk factors encompassing IeffS, whose prognostic power outperformed that of individual features and slightly exceeded that of LIPI. Accordingly, the absence of these risk factors portrayed a favorable IeffS characterizing patients with significantly (P < 0.001) prolonged PFS (median NR vs 2.3 months) and OS (median NR vs 4.1) and greater benefit from ICIs (P < 0.01). We then combined each risk parameter composing IeffS and LIPI (LDHhigh, dNLRhigh), thus defining three distinct prognostic classes. A remarkable impact of IeffS-LIPI integration was documented on survival outcome (PFS, HR = 4.61; 95%CI = 2.32-9.18; P < 0.001; OS, HR=4.03; 95%CI=1.91-8.67; P < 0.001) and ICI-response (AUC=0.90, 95%CI=0.81-0.97, P < 0.001).
Composite risk models based on blood parameters featuring the tumor-host interaction might provide accurate prognostic scores able to predict ICI benefit in NSCLC patients.
We want to characterize the dynamical state of galaxy clusters detected with the Sunyaev–Zeldovich (SZ) effect by Planck and compare them with the dynamical state of clusters selected in X-rays ...survey. We analysed a representative subsample of the Planck SZ catalogue, containing the 132 clusters with the highest signal to noise ratio and characterize their dynamical state using as an indicator the projected offset between the peak of the X-ray emission and the position of the Brightest cluster galaxy. We compare the distribution of this indicator for the Planck SZ-selected sample and three X-ray-selected samples (HIFLUGCS, MACS and REXCESS). The distributions are significantly different and the fraction of relaxed objects is smaller in the Planck sample (52 ± 4 per cent) than in X-ray samples (≃74 per cent) We interpret this result as an indication of different selection effects affecting X-rays (e.g. ‘cool core bias’) and SZ surveys of galaxy clusters.
We quantify the contamination from polarized diffuse Galactic synchrotron and thermal dust emissions to the B modes of the cosmic microwave background (CMB) anisotropies on the degree angular scale, ...using data from the Planck and Wilkinson Microwave Anisotropy Probe (WMAP) satellites. In this way we estimate the amplitude and frequency of the foreground minimum for each analyzed region. We detect both dust and synchrotron signal on degree angular scales and at a 3s confidence level in 28 regions. Here the minimum of the foreground emission is found at frequencies between 60 and 100 GHz with an amplitude expressed in terms of the equivalent tensor-to-scalar ratio, rFG,min, between ~0.06 and ~1. Our results indicate that, with the current sensitivity at low frequency, it is not possible to exclude the presence of synchrotron contamination to CMB cosmological B modes at the level requested to measure a gravitational waves signal with r = 0.01 at frequency 100 GHz anywhere.
Prognostic scores have been developed to estimate the risk of recurrence and the probability of survival after nephrectomy for renal cell carcinoma (RCC). The use of these tools, despite being ...helpful to plan a customized schedule of follow-up, to the patient's tailored counselling and to select individuals who could potentially benefit from adjuvant treatment, currently is not routine, due to their relative complexity and to the lack of histological data (i.e. necrosis).
We developed a simple score called GRade, Age, Nodes and Tumor (GRANT) based on four easily obtained parameters: Fuhrman grade, age, pathological nodal status and pathological tumor size. Patients with 0 or 1 factor are classified as favorable risk, whereas patients with two or more risk factors as unfavorable risk. The large population of RCC patients from the ASSURE adjuvant trial was used as independent dataset for this external validation, to investigate the prognostic value of the new score in terms of disease-free survival and overall survival and to evaluate its possible application as predictive tool. Statistical analyses were carried out by the Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute (Boston, USA) for the ASSURE trial patients’ population.
The performance of the new model is similar to that of the already validated score systems, but its strength, compared with the others already available, is the ease and clarity of its calculation, with great speed of use during the clinical practice. Limitations are the use of the Fuhrman nuclear grade, not valid for rare histologies, and the TNM classification modifications over time.
The GRANT score demonstrated its potential usefulness for clinical practice.
NCT00326898.
COSMOGLOBE DR1 results Eskilt, J. R.; Watts, D. J.; Aurlien, R. ...
Astronomy and astrophysics (Berlin),
11/2023, Letnik:
679
Journal Article
Recenzirano
Odprti dostop
Cosmic birefringence is a parity-violating effect that might have rotated the plane of the linearly polarized light of the cosmic microwave background (CMB) by an angle
β
since its emission. This ...angle has recently been measured to be nonzero at a statistical significance of 3.6
σ
in the official
Planck
PR4 and 9-year WMAP data. In this work, we constrain
β
using the reprocessed B
EYOND
P
LANCK
LFI and C
OSMOGLOBE
DR1 WMAP polarization maps. These novel maps have both lower systematic residuals and a more complete error description than the corresponding official products. Foreground
EB
correlations could bias measurements of
β
, and while thermal dust
EB
emission has been argued to be statistically nonzero, no evidence for synchrotron
EB
power has been reported. Unlike the dust-dominated
Planck
HFI maps, the majority of the LFI and WMAP polarization maps are instead dominated by synchrotron emission. Simultaneously constraining
β
and the polarization miscalibration angle,
α
, of each channel, we find a best-fit value of
β
= 0.35° ±0.70° with LFI and WMAP data only. When including the
Planck
HFI PR4 maps, but fitting
β
separately for dust-dominated,
β
> 70 GHz
, and synchrotron-dominated channels,
β
≤70 GHz
, we find
β
≤70 GHz
= 0.53° ±0.28°. This differs from zero with a statistical significance of 1.9
σ
, and the main contribution to this value comes from the LFI 70 GHz channel. While the statistical significances of these results are low on their own, the measurement derived from the LFI and WMAP synchrotron-dominated maps agrees with the previously reported HFI-dominated constraints, despite the very different astrophysical and instrumental systematics involved in all these experiments.
ESSENTIALS: We performed a pooled analysis of 926 patients with cancer-associated incidental pulmonary embolism (IPE). Vitamin K antagonists (VKA) are associated with a higher risk of major ...hemorrhage. Recurrence risk is comparable after subsegmental and more proximally localized IPE. Our results support low molecular weight heparins over VKA and similar management of subsegmental IPE.
Incidental pulmonary embolism (IPE) is defined as pulmonary embolism (PE) diagnosed on computed tomography scanning not performed for suspected PE. IPE has been estimated to occur in 3.1% of all cancer patients and is a growing challenge for clinicians and patients. Nevertheless, knowledge about the treatment and prognosis of cancer-associated IPE is scarce. We aimed to provide the best available evidence on IPE management.
Incidence rates of symptomatic recurrent venous thromboembolism (VTE), major hemorrhage, and mortality during 6-month follow-up were pooled using individual patient data from studies identified by a systematic literature search. Subgroup analyses based on cancer stage, thrombus localization, and management were performed.
In 926 cancer patients with IPE from 11 cohorts, weighted pooled 6-month risks of recurrent VTE, major hemorrhage and mortality were 5.8% (95% confidence interval CI 3.7-8.3%), 4.7% (95% CI 3.0-6.8%), and 37% (95% CI 28-47%). VTE recurrence risk was comparable under low molecular weight heparins (LMWH) and vitamin K antagonists (VKAs) (6.2% vs. 6.4%; hazard ratio HR 0.9; 95% CI 0.3-3.1), while 12% in untreated patients (HR 2.6; 95% CI 0.91-7.3). Risk of major hemorrhage was higher under VKAs than under LMWH (13% vs. 3.9%; HR 3.9; 95% CI 1.6-10). VTE recurrence risk was comparable in patients with an subsegmental IPE and those with a more proximally localized IPE (HR 1.1; 95% CI 0.50-2.4).
These results support the current recommendation to anticoagulate cancer-associated IPE with LMWH and argue against different management of subsegmental IPE.
We implement support for a cosmological parameter estimation algorithm in
Commander
and quantify its computational efficiency and cost. For a semi-realistic simulation similar to
Planck
LFI 70 GHz, ...we find that the computational cost of producing one single sample is about 20 CPU-hours and that the typical Markov chain correlation length is ∼100 samples. The net effective cost per independent sample is ∼2000 CPU-hours, in comparison with all low-level processing costs of 812 CPU-hours for
Planck
LFI and WMAP in C
OSMOGLOBE
Data Release 1. Thus, although technically possible to run already in its current state, future work should aim to reduce the effective cost per independent sample by one order of magnitude to avoid excessive runtimes, for instance through multi-grid preconditioners and/or derivative-based Markov chain sampling schemes. This work demonstrates the computational feasibility of true Bayesian cosmological parameter estimation with end-to-end error propagation for high-precision CMB experiments without likelihood approximations, but it also highlights the need for additional optimizations before it is ready for full production-level analysis.
In the quest for the faint primordial B-mode polarization of the Cosmic Microwave Background, three are the key requirements for any present or future experiment: an utmost sensitivity, excellent ...control over instrumental systematic effects and over Galactic foreground contamination. Bolometric Interferometry (BI) is a novel technique that matches them all by combining the sensitivity of bolometric detectors, the control of instrumental systematics from interferometry and a software-based, tunable, in-band spectral resolution due to its ability to perform band-splitting during data analysis (spectral imaging). In this paper, we investigate how the spectral imaging capability of BI can help in detecting residual contamination in case an over-simplified model of foreground emission is assumed in the analysis. To mimic this situation, we focus on the next generation of ground-based CMB experiment, CMB-S4, and compare its anticipated sensitivities, frequency and sky coverage with a hypothetical version of the same experiment based on BI, CMB-S4/BI, assuming that lineof-sight (LOS) frequency decorrelation is present in dust emission but is not accounted for during component separation. We show results from a Monte-Carlo analysis based on a parametric component separation method (FGBuster), highlighting how BI has the potential to diagnose the presence of foreground residuals in estimates of the tensor-to-scalar ratio r in the case of unaccounted Galactic dust LOS frequency decorrelation.
BEYONDPLANCK Herman, D.; Hensley, B.; Andersen, K. J. ...
Astronomy and astrophysics (Berlin),
07/2023, Letnik:
675
Journal Article
Recenzirano
Odprti dostop
We constrained the level of polarized anomalous microwave emission (AME) on large angular scales using
Planck
Low-Frequency Instrument (LFI) and WMAP polarization data within a Bayesian cosmic ...microwave background (CMB) analysis framework. We modeled synchrotron emission with a power-law spectral energy distribution, as well as the sum of AME and thermal dust emission through linear regression with the
Planck
High-Frequency Instrument (HFI) 353 GHz data. This template-based dust emission model allowed us to constrain the level of polarized AME while making minimal assumptions on its frequency dependence. We neglected CMB fluctuations, but show through simulations that these fluctuations have a minor impact on the results. We find that the resulting AME polarization fraction confidence limit is sensitive to the polarized synchrotron spectral index prior. In addition, for prior means
β
s
< −3.1 we find an upper limit of
p
AME
max
≲ 0.6% (95% confidence). In contrast, for means
β
s
= −3.0, we find a nominal detection of
p
AME
= 2.5 ± 1.0% (95% confidence). These data are thus not strong enough to simultaneously and robustly constrain both polarized synchrotron emission and AME, and our main result is therefore a constraint on the AME polarization fraction explicitly as a function of
β
s
. Combining the current
Planck
and WMAP observations with measurements from high-sensitivity low-frequency experiments such as C-BASS and QUIJOTE will be critical to improve these limits further.
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