The Lipopolysaccharide from Capnocytophaga canimorsus Reveals an Unexpected Role of the Core-Oligosaccharide in MD-2 Binding

Capnocytophaga canimorsus is a usual member of dog's mouths flora that causes rare but dramatic human infections after dog bites. We determined the structure of C. canimorsus lipid A. The main features are that it is penta-acylated and composed of a “hybrid backbone” lacking the 4′ phosphate and having a 1 phosphoethanolamine (P-Etn) at 2-amino-2-deoxy-d-glucose (GlcN). C. canimorsus LPS was 100 fold less endotoxic than Escherichia coli LPS. Surprisingly, C. canimorsus lipid A was 20,000 fold less endotoxic than the C. canimorsus lipid A-core. This represents the first example in which the core-oligosaccharide dramatically increases endotoxicity of a low endotoxic lipid A. The binding to human myeloid differentiation factor 2 (MD-2) was dramatically increased upon presence of the LPS core on the lipid A, explaining the difference in endotoxicity. Interaction of MD-2, cluster of differentiation antigen 14 (CD14) or LPS-binding protein (LBP) with the negative charge in the 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) of the core might be needed to form the MD-2 – lipid A complex in case the 4′ phosphate is not present

Planck 2018 results. VII. Isotropy and Statistics of the CMB

Analysis of the Planck 2018 data set indicates that the statistical properties of the cosmic microwave background (CMB) temperature anisotropies are in excellent agreement with previous studies using the 2013 and 2015 data releases. In particular, they are consistent with the Gaussian predictions of the $\Lambda$CDM cosmological model, yet also confirm the presence of several so-called "anomalies" on large angular scales. The novelty of the current study, however, lies in being a first attempt at a comprehensive analysis of the statistics of the polarization signal over all angular scales, using either maps of the Stokes parameters, $Q$ and $U$, or the $E$-mode signal derived from these using a new methodology (which we describe in an appendix). Although remarkable progress has been made in reducing the systematic effects that contaminated the 2015 polarization maps on large angular scales, it is still the case that residual systematics (and our ability to simulate them) can limit some tests of non-Gaussianity and isotropy. However, a detailed set of null tests applied to the maps indicates that these issues do not dominate the analysis on intermediate and large angular scales (i.e., $\ell \lesssim 400$). In this regime, no unambiguous detections of cosmological non-Gaussianity, or of anomalies corresponding to those seen in temperature, are claimed. Notably, the stacking of CMB polarization signals centred on the positions of temperature hot and cold spots exhibits excellent agreement with the $\Lambda$CDM cosmological model, and also gives a clear indication of how Planck provides state-of-the-art measurements of CMB temperature and polarization on degree scales

Planck 2018 results. VII. Isotropy and statistics of the CMB

Analysis of the Planck 2018 data set indicates that the statistical properties of the cosmic microwave background (CMB) temperature anisotropies are in excellent agreement with previous studies using the 2013 and 2015 data releases. In particular, they are consistent with the Gaussian predictions of the $\Lambda$CDM cosmological model, yet also confirm the presence of several so-called "anomalies" on large angular scales. The novelty of the current study, however, lies in being a first attempt at a comprehensive analysis of the statistics of the polarization signal over all angular scales, using either maps of the Stokes parameters, $Q$ and $U$, or the $E$-mode signal derived from these using a new methodology (which we describe in an appendix). Although remarkable progress has been made in reducing the systematic effects that contaminated the 2015 polarization maps on large angular scales, it is still the case that residual systematics (and our ability to simulate them) can limit some tests of non-Gaussianity and isotropy. However, a detailed set of null tests applied to the maps indicates that these issues do not dominate the analysis on intermediate and large angular scales (i.e., $\ell \lesssim 400$). In this regime, no unambiguous detections of cosmological non-Gaussianity, or of anomalies corresponding to those seen in temperature, are claimed. Notably, the stacking of CMB polarization signals centred on the positions of temperature hot and cold spots exhibits excellent agreement with the $\Lambda$CDM cosmological model, and also gives a clear indication of how Planck provides state-of-the-art measurements of CMB temperature and polarization on degree scales

Is increased time to diagnosis and treatment in symptomatic cancer associated with poorer outcomes?:Systematic review

background: It is unclear whether more timely cancer diagnosis brings favourable outcomes, with much of the previous evidence, in some cancers, being equivocal. We set out to determine whether there is an association between time to diagnosis, treatment and clinical outcomes, across all cancers for symptomatic presentations. methods: Systematic review of the literature and narrative synthesis. results: We included 177 articles reporting 209 studies. These studies varied in study design, the time intervals assessed and the outcomes reported. Study quality was variable, with a small number of higher-quality studies. Heterogeneity precluded definitive findings. The cancers with more reports of an association between shorter times to diagnosis and more favourable outcomes were breast, colorectal, head and neck, testicular and melanoma. conclusions: This is the first review encompassing many cancer types, and we have demonstrated those cancers in which more evidence of an association between shorter times to diagnosis and more favourable outcomes exists, and where it is lacking. We believe that it is reasonable to assume that efforts to expedite the diagnosis of symptomatic cancer are likely to have benefits for patients in terms of improved survival, earlier-stage diagnosis and improved quality of life, although these benefits vary between cancers

Planck 2015 results: XV. gravitational lensing

We present the most significant measurement of the cosmic microwave background (CMB) lensing potential to date (at a level of 40 sigma), using temperature and polarization data from the Planck 2015 full-mission release. Using a polarization-only estimator we detect lensing at a significance of 5 sigma. We cross-check the accuracy of our measurement using the wide frequency coverage and complementarity of the temperature and polarization measurements. Public products based on this measurement include an estimate of the lensing potential over approximately 70% of the sky, an estimate of the lensing potential power spectrum in bandpowers for the multipole range 40<L<400 and an associated likelihood for cosmological parameter constraints. We find good agreement between our measurement of the lensing potential power spectrum and that found in the best-fitting LCDM model based on the Planck temperature and polarization power spectra. Using the lensing likelihood alone we obtain a percent-level measurement of the parameter combination σ 8 Ω 0.25 m =0.591±0.021 . We combine our determination of the lensing potential with the E-mode polarization also measured by Planck to generate an estimate of the lensing B-mode. We show that this lensing B-mode estimate is correlated with the B-modes observed directly by Planck at the expected level and with a statistical significance of 10 sigma, confirming Planck's sensitivity to this known sky signal. We also correlate our lensing potential estimate with the large-scale temperature anisotropies, detecting a cross-correlation at the 3 sigma level, as expected due to dark energy in the concordance LCDM model

An update of the Worldwide Integrated Assessment (WIA) on systemic insecticides. Part 2: impacts on organisms and ecosystems

New information on the lethal and sublethal effects of neonicotinoids and fipronil on organisms is presented in this review, complementing the previous WIA in 2015. The high toxicity of these systemic insecticides to invertebrates has been confirmed and expanded to include more species and compounds. Most of the recent research has focused on bees and the sublethal and ecological impacts these insecticides have on pollinators. Toxic effects on other invertebrate taxa also covered predatory and parasitoid natural enemies and aquatic arthropods. Little, while not much new information has been gathered on soil organisms. The impact on marine coastal ecosystems is still largely uncharted. The chronic lethality of neonicotinoids to insects and crustaceans, and the strengthened evidence that these chemicals also impair the immune system and reproduction, highlights the dangers of this particular insecticidal classneonicotinoids and fipronil. , withContinued large scale – mostly prophylactic – use of these persistent organochlorine pesticides has the potential to greatly decreasecompletely eliminate populations of arthropods in both terrestrial and aquatic environments. Sublethal effects on fish, reptiles, frogs, birds and mammals are also reported, showing a better understanding of the mechanisms of toxicity of these insecticides in vertebrates, and their deleterious impacts on growth, reproduction and neurobehaviour of most of the species tested. This review concludes with a summary of impacts on the ecosystem services and functioning, particularly on pollination, soil biota and aquatic invertebrate communities, thus reinforcing the previous WIA conclusions (van der Sluijs et al. 2015)

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Cosmology intertwined: A review of the particle physics, astrophysics, and cosmology associated with the cosmological tensions and anomalies

The standard Cold Dark Matter (CDM) cosmological model provides a good description of a wide range of astrophysical and cosmological data. However, there are a few big open questions that make the standard model look like an approximation to a more realistic scenario yet to be found. In this paper, we list a few important goals that need to be addressed in the next decade, taking into account the current discordances between the different cosmological probes, such as the disagreement in the value of the Hubble constant H0, the σ8–S8 tension, and other less statistically significant anomalies. While these discordances can still be in part the result of systematic errors, their persistence after several years of accurate analysis strongly hints at cracks in the standard cosmological scenario and the necessity for new physics or generalisations beyond the standard model. In this paper, we focus on the 5.0 σ tension between the Planck CMB estimate of the Hubble constant H0 and the SH0ES collaboration measurements. After showing the H0 evaluations made from different teams using different methods and geometric calibrations, we list a few interesting new physics models that could alleviate this tension and discuss how the next decade’s experiments will be crucial. Moreover, we focus on the tension of the Planck CMB data with weak lensing measurements and redshift surveys, about the value of the matter energy density m, and the amplitude or rate of the growth of structure (σ8, f σ8). We list a few interesting models proposed for alleviating this tension, and we discuss the importance of trying to fit a full array of data with a single model and not just one parameter at a time. Additionally, we present a wide range of other less discussed anomalies at a statistical significance level lower than the H0–S8 tensions which may also constitute hints towards new physics, and we discuss possible generic theoretical approaches that can collectively explain the non-standard nature of these signals. Finally, we give an overview of upgraded experiments and next-generation space missions and facilities on Earth that will be of crucial importance to address all these open questions

Planck 2015 results XV. Gravitational lensing

We present the most significant measurement of the cosmic microwave background (CMB) lensing potential to date (at a level of 40σ), using temperature and polarization data from the Planck 2015 full-mission release. Using a polarization-only estimator, we detect lensing at a significance of 5σ. We cross-check the accuracy of our measurement using the wide frequency coverage and complementarity of the temperature and polarization measurements. Public products based on this measurement include an estimate of the lensing potential over approximately 70% of the sky, an estimate of the lensing potential power spectrum in bandpowers for the multipole range 40 ≤ L ≤ 400, and an associated likelihood for cosmological parameter constraints. We find good agreement between our measurement of the lensing potential power spectrum and that found in the ΛCDM model that best fits the Planck temperature and polarization power spectra. Using the lensing likelihood alone we obtain a percent-level measurement of the parameter combination σ8Ω0.25m = 0.591 ± 0.021. We combine our determination of the lensing potential with the E-mode polarization, also measured by Planck, to generate an estimate of the lensing B-mode. We show that this lensing B-mode estimate is correlated with the B-modes observed directly by Planck at the expected level and with a statistical significance of 10σ, confirming Planck’s sensitivity to this known sky signal. We also correlate our lensing potential estimate with the large-scale temperature anisotropies, detecting a cross-correlation at the 3σ level, as expected because of dark energy in the concordance ΛCDM model

Planck 2015 results XXVI. The Second Planck Catalogue of Compact Sources

The Second Planck Catalogue of Compact Sources is a list of discrete objects detected in single-frequency maps from the full duration of the Planck mission and supersedes previous versions. It consists of compact sources, both Galactic and extragalactic, detected over the entire sky. Compact sources detected in the lower frequency channels are assigned to the PCCS2, while at higher frequencies they are assigned to one of two subcatalogues, the PCCS2 or PCCS2E, depending on their location on the sky. The first of these (PCCS2) covers most of the sky and allows the user to produce subsamples at higher reliabilities than the target 80% integral reliability of the catalogue. The second ( PCCS2E) contains sources detected in sky regions where the diffuse emission makes it difficult to quantify the reliability of the detections. Both the PCCS2 and PCCS2E include polarization measurements, in the form of polarized flux densities, or upper limits, and orientation angles for all seven polarization-sensitive Planck channels. The improved data-processing of the full-mission maps and their reduced noise levels allow us to increase the number of objects in the catalogue, improving its completeness for the target 80% reliability as compared with the previous versions, the PCCS and the Early Release Compact Source Catalogue (ERCSC)