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Showing papers by "Sapienza University of Rome published in 2016"


Journal ArticleDOI
Peter A. R. Ade1, Nabila Aghanim2, Monique Arnaud3, M. Ashdown4  +334 moreInstitutions (82)
TL;DR: In this article, the authors present a cosmological analysis based on full-mission Planck observations of temperature and polarization anisotropies of the cosmic microwave background (CMB) radiation.
Abstract: This paper presents cosmological results based on full-mission Planck observations of temperature and polarization anisotropies of the cosmic microwave background (CMB) radiation. Our results are in very good agreement with the 2013 analysis of the Planck nominal-mission temperature data, but with increased precision. The temperature and polarization power spectra are consistent with the standard spatially-flat 6-parameter ΛCDM cosmology with a power-law spectrum of adiabatic scalar perturbations (denoted “base ΛCDM” in this paper). From the Planck temperature data combined with Planck lensing, for this cosmology we find a Hubble constant, H0 = (67.8 ± 0.9) km s-1Mpc-1, a matter density parameter Ωm = 0.308 ± 0.012, and a tilted scalar spectral index with ns = 0.968 ± 0.006, consistent with the 2013 analysis. Note that in this abstract we quote 68% confidence limits on measured parameters and 95% upper limits on other parameters. We present the first results of polarization measurements with the Low Frequency Instrument at large angular scales. Combined with the Planck temperature and lensing data, these measurements give a reionization optical depth of τ = 0.066 ± 0.016, corresponding to a reionization redshift of . These results are consistent with those from WMAP polarization measurements cleaned for dust emission using 353-GHz polarization maps from the High Frequency Instrument. We find no evidence for any departure from base ΛCDM in the neutrino sector of the theory; for example, combining Planck observations with other astrophysical data we find Neff = 3.15 ± 0.23 for the effective number of relativistic degrees of freedom, consistent with the value Neff = 3.046 of the Standard Model of particle physics. The sum of neutrino masses is constrained to ∑ mν < 0.23 eV. The spatial curvature of our Universe is found to be very close to zero, with | ΩK | < 0.005. Adding a tensor component as a single-parameter extension to base ΛCDM we find an upper limit on the tensor-to-scalar ratio of r0.002< 0.11, consistent with the Planck 2013 results and consistent with the B-mode polarization constraints from a joint analysis of BICEP2, Keck Array, and Planck (BKP) data. Adding the BKP B-mode data to our analysis leads to a tighter constraint of r0.002 < 0.09 and disfavours inflationarymodels with a V(φ) ∝ φ2 potential. The addition of Planck polarization data leads to strong constraints on deviations from a purely adiabatic spectrum of fluctuations. We find no evidence for any contribution from isocurvature perturbations or from cosmic defects. Combining Planck data with other astrophysical data, including Type Ia supernovae, the equation of state of dark energy is constrained to w = −1.006 ± 0.045, consistent with the expected value for a cosmological constant. The standard big bang nucleosynthesis predictions for the helium and deuterium abundances for the best-fit Planck base ΛCDM cosmology are in excellent agreement with observations. We also constraints on annihilating dark matter and on possible deviations from the standard recombination history. In neither case do we find no evidence for new physics. The Planck results for base ΛCDM are in good agreement with baryon acoustic oscillation data and with the JLA sample of Type Ia supernovae. However, as in the 2013 analysis, the amplitude of the fluctuation spectrum is found to be higher than inferred from some analyses of rich cluster counts and weak gravitational lensing. We show that these tensions cannot easily be resolved with simple modifications of the base ΛCDM cosmology. Apart from these tensions, the base ΛCDM cosmology provides an excellent description of the Planck CMB observations and many other astrophysical data sets.

10,728 citations


Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, Matthew Abernathy1  +1008 moreInstitutions (96)
TL;DR: This is the first direct detection of gravitational waves and the first observation of a binary black hole merger, and these observations demonstrate the existence of binary stellar-mass black hole systems.
Abstract: On September 14, 2015 at 09:50:45 UTC the two detectors of the Laser Interferometer Gravitational-Wave Observatory simultaneously observed a transient gravitational-wave signal. The signal sweeps upwards in frequency from 35 to 250 Hz with a peak gravitational-wave strain of $1.0 \times 10^{-21}$. It matches the waveform predicted by general relativity for the inspiral and merger of a pair of black holes and the ringdown of the resulting single black hole. The signal was observed with a matched-filter signal-to-noise ratio of 24 and a false alarm rate estimated to be less than 1 event per 203 000 years, equivalent to a significance greater than 5.1 {\sigma}. The source lies at a luminosity distance of $410^{+160}_{-180}$ Mpc corresponding to a redshift $z = 0.09^{+0.03}_{-0.04}$. In the source frame, the initial black hole masses are $36^{+5}_{-4} M_\odot$ and $29^{+4}_{-4} M_\odot$, and the final black hole mass is $62^{+4}_{-4} M_\odot$, with $3.0^{+0.5}_{-0.5} M_\odot c^2$ radiated in gravitational waves. All uncertainties define 90% credible intervals.These observations demonstrate the existence of binary stellar-mass black hole systems. This is the first direct detection of gravitational waves and the first observation of a binary black hole merger.

9,596 citations


Journal ArticleDOI
Daniel J. Klionsky1, Kotb Abdelmohsen2, Akihisa Abe3, Joynal Abedin4  +2519 moreInstitutions (695)
TL;DR: In this paper, the authors present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macro-autophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

5,187 citations


Journal ArticleDOI
Haidong Wang1, Mohsen Naghavi1, Christine Allen1, Ryan M Barber1  +841 moreInstitutions (293)
TL;DR: The Global Burden of Disease 2015 Study provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015, finding several countries in sub-Saharan Africa had very large gains in life expectancy, rebounding from an era of exceedingly high loss of life due to HIV/AIDS.

4,804 citations


Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, M. R. Abernathy3  +970 moreInstitutions (114)
TL;DR: This second gravitational-wave observation provides improved constraints on stellar populations and on deviations from general relativity.
Abstract: We report the observation of a gravitational-wave signal produced by the coalescence of two stellar-mass black holes. The signal, GW151226, was observed by the twin detectors of the Laser Interferometer Gravitational-Wave Observatory (LIGO) on December 26, 2015 at 03:38:53 UTC. The signal was initially identified within 70 s by an online matched-filter search targeting binary coalescences. Subsequent off-line analyses recovered GW151226 with a network signal-to-noise ratio of 13 and a significance greater than 5 σ. The signal persisted in the LIGO frequency band for approximately 1 s, increasing in frequency and amplitude over about 55 cycles from 35 to 450 Hz, and reached a peak gravitational strain of 3.4+0.7−0.9×10−22. The inferred source-frame initial black hole masses are 14.2+8.3−3.7M⊙ and 7.5+2.3−2.3M⊙ and the final black hole mass is 20.8+6.1−1.7M⊙. We find that at least one of the component black holes has spin greater than 0.2. This source is located at a luminosity distance of 440+180−190 Mpc corresponding to a redshift 0.09+0.03−0.04. All uncertainties define a 90 % credible interval. This second gravitational-wave observation provides improved constraints on stellar populations and on deviations from general relativity.

3,448 citations


Journal ArticleDOI
23 Feb 2016-JAMA
TL;DR: Clinician recognition of ARDS was associated with higher PEEP, greater use of neuromuscular blockade, and prone positioning, which indicates the potential for improvement in the management of patients with ARDS.
Abstract: IMPORTANCE Limited information exists about the epidemiology, recognition, management, and outcomes of patients with the acute respiratory distress syndrome (ARDS). OBJECTIVES To evaluate intensive ...

3,259 citations


Journal ArticleDOI
Nicholas J Kassebaum1, Megha Arora1, Ryan M Barber1, Zulfiqar A Bhutta2  +679 moreInstitutions (268)
TL;DR: In this paper, the authors used the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015.

1,533 citations


Journal ArticleDOI
TL;DR: A massive quantitative analysis of Facebook shows that information related to distinct narratives––conspiracy theories and scientific news––generates homogeneous and polarized communities having similar information consumption patterns, and derives a data-driven percolation model of rumor spreading that demonstrates that homogeneity and polarization are the main determinants for predicting cascades’ size.
Abstract: The wide availability of user-provided content in online social media facilitates the aggregation of people around common interests, worldviews, and narratives. However, the World Wide Web (WWW) also allows for the rapid dissemination of unsubstantiated rumors and conspiracy theories that often elicit rapid, large, but naive social responses such as the recent case of Jade Helm 15––where a simple military exercise turned out to be perceived as the beginning of a new civil war in the United States. In this work, we address the determinants governing misinformation spreading through a thorough quantitative analysis. In particular, we focus on how Facebook users consume information related to two distinct narratives: scientific and conspiracy news. We find that, although consumers of scientific and conspiracy stories present similar consumption patterns with respect to content, cascade dynamics differ. Selective exposure to content is the primary driver of content diffusion and generates the formation of homogeneous clusters, i.e., “echo chambers.” Indeed, homogeneity appears to be the primary driver for the diffusion of contents and each echo chamber has its own cascade dynamics. Finally, we introduce a data-driven percolation model mimicking rumor spreading and we show that homogeneity and polarization are the main determinants for predicting cascades’ size.

1,457 citations


Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, M. R. Abernathy1  +976 moreInstitutions (107)
TL;DR: It is found that the final remnant's mass and spin, as determined from the low-frequency and high-frequency phases of the signal, are mutually consistent with the binary black-hole solution in general relativity.
Abstract: The LIGO detection of GW150914 provides an unprecedented opportunity to study the two-body motion of a compact-object binary in the large-velocity, highly nonlinear regime, and to witness the final merger of the binary and the excitation of uniquely relativistic modes of the gravitational field. We carry out several investigations to determine whether GW150914 is consistent with a binary black-hole merger in general relativity. We find that the final remnant’s mass and spin, as determined from the low-frequency (inspiral) and high-frequency (postinspiral) phases of the signal, are mutually consistent with the binary black-hole solution in general relativity. Furthermore, the data following the peak of GW150914 are consistent with the least-damped quasinormal mode inferred from the mass and spin of the remnant black hole. By using waveform models that allow for parametrized general-relativity violations during the inspiral and merger phases, we perform quantitative tests on the gravitational-wave phase in the dynamical regime and we determine the first empirical bounds on several high-order post-Newtonian coefficients. We constrain the graviton Compton wavelength, assuming that gravitons are dispersed in vacuum in the same way as particles with mass, obtaining a 90%-confidence lower bound of 1013 km. In conclusion, within our statistical uncertainties, we find no evidence for violations of general relativity in the genuinely strong-field regime of gravity.

1,421 citations


Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, Matthew Abernathy3  +978 moreInstitutions (112)
TL;DR: The first observational run of the Advanced LIGO detectors, from September 12, 2015 to January 19, 2016, saw the first detections of gravitational waves from binary black hole mergers as discussed by the authors.
Abstract: The first observational run of the Advanced LIGO detectors, from September 12, 2015 to January 19, 2016, saw the first detections of gravitational waves from binary black hole mergers. In this paper we present full results from a search for binary black hole merger signals with total masses up to 100M⊙ and detailed implications from our observations of these systems. Our search, based on general-relativistic models of gravitational wave signals from binary black hole systems, unambiguously identified two signals, GW150914 and GW151226, with a significance of greater than 5σ over the observing period. It also identified a third possible signal, LVT151012, with substantially lower significance, which has a 87% probability of being of astrophysical origin. We provide detailed estimates of the parameters of the observed systems. Both GW150914 and GW151226 provide an unprecedented opportunity to study the two-body motion of a compact-object binary in the large velocity, highly nonlinear regime. We do not observe any deviations from general relativity, and place improved empirical bounds on several high-order post-Newtonian coefficients. From our observations we infer stellar-mass binary black hole merger rates lying in the range 9−240Gpc−3yr−1. These observations are beginning to inform astrophysical predictions of binary black hole formation rates, and indicate that future observing runs of the Advanced detector network will yield many more gravitational wave detections.

1,172 citations


Journal ArticleDOI
Nabila Aghanim1, Monique Arnaud2, M. Ashdown3, J. Aumont1  +291 moreInstitutions (73)
TL;DR: In this article, the authors present the Planck 2015 likelihoods, statistical descriptions of the 2-point correlation functions of the cosmic microwave background (CMB) temperature and polarization fluctuations that account for relevant uncertainties.
Abstract: This paper presents the Planck 2015 likelihoods, statistical descriptions of the 2-point correlationfunctions of the cosmic microwave background (CMB) temperature and polarization fluctuations that account for relevant uncertainties, both instrumental and astrophysical in nature. They are based on the same hybrid approach used for the previous release, i.e., a pixel-based likelihood at low multipoles (l< 30) and a Gaussian approximation to the distribution of cross-power spectra at higher multipoles. The main improvements are the use of more and better processed data and of Planck polarization information, along with more detailed models of foregrounds and instrumental uncertainties. The increased redundancy brought by more than doubling the amount of data analysed enables further consistency checks and enhanced immunity to systematic effects. It also improves the constraining power of Planck, in particular with regard to small-scale foreground properties. Progress in the modelling of foreground emission enables the retention of a larger fraction of the sky to determine the properties of the CMB, which also contributes to the enhanced precision of the spectra. Improvements in data processing and instrumental modelling further reduce uncertainties. Extensive tests establish the robustness and accuracy of the likelihood results, from temperature alone, from polarization alone, and from their combination. For temperature, we also perform a full likelihood analysis of realistic end-to-end simulations of the instrumental response to the sky, which were fed into the actual data processing pipeline; this does not reveal biases from residual low-level instrumental systematics. Even with the increase in precision and robustness, the ΛCDM cosmological model continues to offer a very good fit to the Planck data. The slope of the primordial scalar fluctuations, n_s, is confirmed smaller than unity at more than 5σ from Planck alone. We further validate the robustness of the likelihood results against specific extensions to the baseline cosmology, which are particularly sensitive to data at high multipoles. For instance, the effective number of neutrino species remains compatible with the canonical value of 3.046. For this first detailed analysis of Planck polarization spectra, we concentrate at high multipoles on the E modes, leaving the analysis of the weaker B modes to future work. At low multipoles we use temperature maps at all Planck frequencies along with a subset of polarization data. These data take advantage of Planck’s wide frequency coverage to improve the separation of CMB and foreground emission. Within the baseline ΛCDM cosmology this requires τ = 0.078 ± 0.019 for the reionization optical depth, which is significantly lower than estimates without the use of high-frequency data for explicit monitoring of dust emission. At high multipoles we detect residual systematic errors in E polarization, typically at the μK^2 level; we therefore choose to retain temperature information alone for high multipoles as the recommended baseline, in particular for testing non-minimal models. Nevertheless, the high-multipole polarization spectra from Planck are already good enough to enable a separate high-precision determination of the parameters of the ΛCDM model, showing consistency with those established independently from temperature information alone.

Journal ArticleDOI
TL;DR: This Consensus Statement aims to provide valuable information on classifications, pathological features, risk factors, cells of origin, genetic and epigenetic modifications and current therapies available for this cancer.
Abstract: Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies with features of biliary tract differentiation. CCA is the second most common primary liver tumour and the incidence is increasing worldwide. CCA has high mortality owing to its aggressiveness, late diagnosis and refractory nature. In May 2015, the "European Network for the Study of Cholangiocarcinoma" (ENS-CCA: www.enscca.org or www.cholangiocarcinoma.eu) was created to promote and boost international research collaboration on the study of CCA at basic, translational and clinical level. In this Consensus Statement, we aim to provide valuable information on classifications, pathological features, risk factors, cells of origin, genetic and epigenetic modifications and current therapies available for this cancer. Moreover, future directions on basic and clinical investigations and plans for the ENS-CCA are highlighted.


Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, Matthew Abernathy1  +984 moreInstitutions (116)
TL;DR: The data around the time of the event were analyzed coherently across the LIGO network using a suite of accurate waveform models that describe gravitational waves from a compact binary system in general relativity.
Abstract: On September 14, 2015, the Laser Interferometer Gravitational-wave Observatory (LIGO) detected a gravitational-wave transient (GW150914); we characterise the properties of the source and its parameters. The data around the time of the event were analysed coherently across the LIGO network using a suite of accurate waveform models that describe gravitational waves from a compact binary system in general relativity. GW150914 was produced by a nearly equal mass binary black hole of $36^{+5}_{-4} M_\odot$ and $29^{+4}_{-4} M_\odot$ (for each parameter we report the median value and the range of the 90% credible interval). The dimensionless spin magnitude of the more massive black hole is bound to be $0.7$ (at 90% probability). The luminosity distance to the source is $410^{+160}_{-180}$ Mpc, corresponding to a redshift $0.09^{+0.03}_{-0.04}$ assuming standard cosmology. The source location is constrained to an annulus section of $590$ deg$^2$, primarily in the southern hemisphere. The binary merges into a black hole of $62^{+4}_{-4} M_\odot$ and spin $0.67^{+0.05}_{-0.07}$. This black hole is significantly more massive than any other known in the stellar-mass regime.

Journal ArticleDOI
TL;DR: This paper features the first comprehensive and critical account of European syntaxa and synthesizes more than 100 yr of classification effort by European phytosociologists.
Abstract: Aims: Vegetation classification consistent with the Braun-Blanquet approach is widely used in Europe for applied vegetation science, conservation planning and land management. During the long history of syntaxonomy, many concepts and names of vegetation units have been proposed, but there has been no single classification system integrating these units. Here we (1) present a comprehensive, hierarchical, syntaxonomic system of alliances, orders and classes of Braun-Blanquet syntaxonomy for vascular plant, bryophyte and lichen, and algal communities of Europe; (2) briefly characterize in ecological and geographic terms accepted syntaxonomic concepts; (3) link available synonyms to these accepted concepts; and (4) provide a list of diagnostic species for all classes. LocationEuropean mainland, Greenland, Arctic archipelagos (including Iceland, Svalbard, Novaya Zemlya), Canary Islands, Madeira, Azores, Caucasus, Cyprus. Methods: We evaluated approximately 10000 bibliographic sources to create a comprehensive list of previously proposed syntaxonomic units. These units were evaluated by experts for their floristic and ecological distinctness, clarity of geographic distribution and compliance with the nomenclature code. Accepted units were compiled into three systems of classes, orders and alliances (EuroVegChecklist, EVC) for communities dominated by vascular plants (EVC1), bryophytes and lichens (EVC2) and algae (EVC3). Results: EVC1 includes 109 classes, 300 orders and 1108 alliances; EVC2 includes 27 classes, 53 orders and 137 alliances, and EVC3 includes 13 classes, 24 orders and 53 alliances. In total 13448 taxa were assigned as indicator species to classes of EVC1, 2087 to classes of EVC2 and 368 to classes of EVC3. Accepted syntaxonomic concepts are summarized in a series of appendices, and detailed information on each is accessible through the software tool EuroVegBrowser. Conclusions: This paper features the first comprehensive and critical account of European syntaxa and synthesizes more than 100 yr of classification effort by European phytosociologists. It aims to document and stabilize the concepts and nomenclature of syntaxa for practical uses, such as calibration of habitat classification used by the European Union, standardization of terminology for environmental assessment, management and conservation of nature areas, landscape planning and education. The presented classification systems provide a baseline for future development and revision of European syntaxonomy.

Journal ArticleDOI
Peter A. R. Ade1, Nabila Aghanim2, Monique Arnaud3, M. Ashdown4  +301 moreInstitutions (72)
TL;DR: In this paper, the implications of Planck data for models of dark energy (DE) and modified gravity (MG) beyond the standard cosmological constant scenario were studied, and it was shown that the density of DE at early times has to be below 2% of the critical density, even when forced to play a role for z < 50.
Abstract: We study the implications of Planck data for models of dark energy (DE) and modified gravity (MG) beyond the standard cosmological constant scenario. We start with cases where the DE only directly affects the background evolution, considering Taylor expansions of the equation of state w(a), as well as principal component analysis and parameterizations related to the potential of a minimally coupled DE scalar field. When estimating the density of DE at early times, we significantly improve present constraints and find that it has to be below ~2% (at 95% confidence) of the critical density, even when forced to play a role for z < 50 only. We then move to general parameterizations of the DE or MG perturbations that encompass both effective field theories and the phenomenology of gravitational potentials in MG models. Lastly, we test a range of specific models, such as k-essence, f(R) theories, and coupled DE. In addition to the latest Planck data, for our main analyses, we use background constraints from baryonic acoustic oscillations, type-Ia supernovae, and local measurements of the Hubble constant. We further show the impact of measurements of the cosmological perturbations, such as redshift-space distortions and weak gravitational lensing. These additional probes are important tools for testing MG models and for breaking degeneracies that are still present in the combination of Planck and background data sets. All results that include only background parameterizations (expansion of the equation of state, early DE, general potentials in minimally-coupled scalar fields or principal component analysis) are in agreement with ΛCDM. When testing models that also change perturbations (even when the background is fixed to ΛCDM), some tensions appear in a few scenarios: the maximum one found is ~2σ for Planck TT+lowP when parameterizing observables related to the gravitational potentials with a chosen time dependence; the tension increases to, at most, 3σ when external data sets are included. It however disappears when including CMB lensing.

Journal ArticleDOI
11 Nov 2016-Science
TL;DR: The full range and scale of climate change effects on global biodiversity that have been observed in natural systems are described, and a set of core ecological processes that underpin ecosystem functioning and support services to people are identified.
Abstract: Most ecological processes now show responses to anthropogenic climate change. In terrestrial, freshwater, and marine ecosystems, species are changing genetically, physiologically, morphologically, and phenologically and are shifting their distributions, which affects food webs and results in new interactions. Disruptions scale from the gene to the ecosystem and have documented consequences for people, including unpredictable fisheries and crop yields, loss of genetic diversity in wild crop varieties, and increasing impacts of pests and diseases. In addition to the more easily observed changes, such as shifts in flowering phenology, we argue that many hidden dynamics, such as genetic changes, are also taking place. Understanding shifts in ecological processes can guide human adaptation strategies. In addition to reducing greenhouse gases, climate action and policy must therefore focus equally on strategies that safeguard biodiversity and ecosystems.

Journal ArticleDOI
TL;DR: The finding that small non-coding RNAs (ncRNAs) are able to control gene expression in a sequence specific manner has had a massive impact on biology and it is becoming evident that miRNAs also have specific nuclear functions.
Abstract: The finding that small non-coding RNAs (ncRNAs) are able to control gene expression in a sequence specific manner has had a massive impact on biology. Recent improvements in high throughput sequencing and computational prediction methods have allowed the discovery and classification of several types of ncRNAs. Based on their precursor structures, biogenesis pathways and modes of action, ncRNAs are classified as small interfering RNAs (siRNAs), microRNAs (miRNAs), PIWI-interacting RNAs (piRNAs), endogenous small interfering RNAs (endo-siRNAs or esiRNAs), promoter associate RNAs (pRNAs), small nucleolar RNAs (snoRNAs) and sno-derived RNAs. Among these, miRNAs appear as important cytoplasmic regulators of gene expression. miRNAs act as post-transcriptional regulators of their messenger RNA (mRNA) targets via mRNA degradation and/or translational repression. However, it is becoming evident that miRNAs also have specific nuclear functions. Among these, the most studied and debated activity is the miRNA-guided transcriptional control of gene expression. Although available data detail quite precisely the effectors of this activity, the mechanisms by which miRNAs identify their gene targets to control transcription are still a matter of debate. Here, we focus on nuclear functions of miRNAs and on alternative mechanisms of target recognition, at the promoter lavel, by miRNAs in carrying out transcriptional gene silencing.

Journal ArticleDOI
TL;DR: The final results of the search for the lepton flavour violating decay were presented in this paper, based on the full dataset collected by the MEG experiment at the Paul Scherrer Institut in the period 2009-2013.
Abstract: The final results of the search for the lepton flavour violating decay $$\mathrm {\mu }^+ \rightarrow \mathrm {e}^+ \mathrm {\gamma }$$ based on the full dataset collected by the MEG experiment at the Paul Scherrer Institut in the period 2009–2013 and totalling $$7.5\times 10^{14}$$ stopped muons on target are presented. No significant excess of events is observed in the dataset with respect to the expected background and a new upper limit on the branching ratio of this decay of $$ \mathcal{B} (\mu ^+ \rightarrow \mathrm{e}^+ \gamma ) < 4.2 \times 10^{-13}$$ (90 % confidence level) is established, which represents the most stringent limit on the existence of this decay to date.

Journal ArticleDOI
08 Jun 2016-Pain
TL;DR: A revised grading system of possible, probable, and definite neuropathic pain from 2008 is presented with an adjusted order, better reflecting clinical practice, improvements in the specifications, and a word of caution that even the “definite” level of neuropathicPain does not always indicate causality.
Abstract: The redefinition of neuropathic pain as "pain arising as a direct consequence of a lesion or disease affecting the somatosensory system," which was suggested by the International Association for the Study of Pain (IASP) Special Interest Group on Neuropathic Pain (NeuPSIG) in 2008, has been widely accepted. In contrast, the proposed grading system of possible, probable, and definite neuropathic pain from 2008 has been used to a lesser extent. Here, we report a citation analysis of the original NeuPSIG grading paper of 2008, followed by an analysis of its use by an expert panel and recommendations for an improved grading system. As of February, 2015, 608 eligible articles in Scopus cited the paper, 414 of which cited the neuropathic pain definition. Of 220 clinical studies citing the paper, 56 had used the grading system. The percentage using the grading system increased from 5% in 2009 to 30% in 2014. Obstacles to a wider use of the grading system were identified, including (1) questions about the relative significance of confirmatory tests, (2) the role of screening tools, and (3) uncertainties about what is considered a neuroanatomically plausible pain distribution. Here, we present a revised grading system with an adjusted order, better reflecting clinical practice, improvements in the specifications, and a word of caution that even the "definite" level of neuropathic pain does not always indicate causality. In addition, we add a table illustrating the area of pain and sensory abnormalities in common neuropathic pain conditions and propose areas for further research.

Journal ArticleDOI
B. P. Abbott1, Richard J. Abbott1, T. D. Abbott2, Matthew Abernathy1  +961 moreInstitutions (100)
TL;DR: The discovery of the GW150914 with the Advanced LIGO detectors provides the first observational evidence for the existence of binary black-hole systems that inspiral and merge within the age of the Universe as mentioned in this paper.
Abstract: The discovery of the gravitational-wave source GW150914 with the Advanced LIGO detectors provides the first observational evidence for the existence of binary black-hole systems that inspiral and merge within the age of the Universe. Such black-hole mergers have been predicted in two main types of formation models, involving isolated binaries in galactic fields or dynamical interactions in young and old dense stellar environments. The measured masses robustly demonstrate that relatively "heavy" black holes (≳25M⊙) can form in nature. This discovery implies relatively weak massive-star winds and thus the formation of GW150914 in an environment with metallicity lower than ∼1/2 of the solar value. The rate of binary black-hole mergers inferred from the observation of GW150914 is consistent with the higher end of rate predictions (≳1Gpc−3yr−1) from both types of formation models. The low measured redshift (z∼0.1) of GW150914 and the low inferred metallicity of the stellar progenitor imply either binary black-hole formation in a low-mass galaxy in the local Universe and a prompt merger, or formation at high redshift with a time delay between formation and merger of several Gyr. This discovery motivates further studies of binary-black-hole formation astrophysics. It also has implications for future detections and studies by Advanced LIGO and Advanced Virgo, and gravitational-wave detectors in space.

Journal ArticleDOI
S. Adrián-Martínez1, M. Ageron2, Felix Aharonian3, Sebastiano Aiello  +243 moreInstitutions (24)
TL;DR: In this article, the main objectives of the KM3NeT Collaboration are (i) the discovery and subsequent observation of high-energy neutrino sources in the Universe and (ii) the determination of the mass hierarchy of neutrinos.
Abstract: The main objectives of the KM3NeT Collaboration are (i) the discovery and subsequent observation of high-energy neutrino sources in the Universe and (ii) the determination of the mass hierarchy of neutrinos. These objectives are strongly motivated by two recent important discoveries, namely: (1) the high-energy astrophysical neutrino signal reported by IceCube and (2) the sizable contribution of electron neutrinos to the third neutrino mass eigenstate as reported by Daya Bay, Reno and others. To meet these objectives, the KM3NeT Collaboration plans to build a new Research Infrastructure consisting of a network of deep-sea neutrino telescopes in the Mediterranean Sea. A phased and distributed implementation is pursued which maximises the access to regional funds, the availability of human resources and the synergistic opportunities for the Earth and sea sciences community. Three suitable deep-sea sites are selected, namely off-shore Toulon (France), Capo Passero (Sicily, Italy) and Pylos (Peloponnese, Greece). The infrastructure will consist of three so-called building blocks. A building block comprises 115 strings, each string comprises 18 optical modules and each optical module comprises 31 photo-multiplier tubes. Each building block thus constitutes a three-dimensional array of photo sensors that can be used to detect the Cherenkov light produced by relativistic particles emerging from neutrino interactions. Two building blocks will be sparsely configured to fully explore the IceCube signal with similar instrumented volume, different methodology, improved resolution and complementary field of view, including the galactic plane. One building block will be densely configured to precisely measure atmospheric neutrino oscillations.

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Peter A. R. Ade1, Nabila Aghanim2, Monique Arnaud3, Frederico Arroja4  +306 moreInstitutions (75)
TL;DR: In this article, the Planck full mission cosmic microwave background (CMB) temperature and E-mode polarization maps are analysed to obtain constraints on primordial non-Gaussianity (NG).
Abstract: The Planck full mission cosmic microwave background (CMB) temperature and E-mode polarization maps are analysed to obtain constraints on primordial non-Gaussianity (NG). Using three classes of optimal bispectrum estimators – separable template-fitting (KSW), binned, and modal – we obtain consistent values for the primordial local, equilateral, and orthogonal bispectrum amplitudes, quoting as our final result from temperature alone ƒlocalNL = 2.5 ± 5.7, ƒequilNL= -16 ± 70, , and ƒorthoNL = -34 ± 32 (68% CL, statistical). Combining temperature and polarization data we obtain ƒlocalNL = 0.8 ± 5.0, ƒequilNL= -4 ± 43, and ƒorthoNL = -26 ± 21 (68% CL, statistical). The results are based on comprehensive cross-validation of these estimators on Gaussian and non-Gaussian simulations, are stable across component separation techniques, pass an extensive suite of tests, and are consistent with estimators based on measuring the Minkowski functionals of the CMB. The effect of time-domain de-glitching systematics on the bispectrum is negligible. In spite of these test outcomes we conservatively label the results including polarization data as preliminary, owing to a known mismatch of the noise model in simulations and the data. Beyond estimates of individual shape amplitudes, we present model-independent, three-dimensional reconstructions of the Planck CMB bispectrum and derive constraints on early universe scenarios that generate primordial NG, including general single-field models of inflation, axion inflation, initial state modifications, models producing parity-violating tensor bispectra, and directionally dependent vector models. We present a wide survey of scale-dependent feature and resonance models, accounting for the “look elsewhere” effect in estimating the statistical significance of features. We also look for isocurvature NG, and find no signal, but we obtain constraints that improve significantly with the inclusion of polarization. The primordial trispectrum amplitude in the local model is constrained to be

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Dominik Sturm1, Dominik Sturm2, Brent A. Orr3, Umut H. Toprak1, Volker Hovestadt1, David T.W. Jones1, David Capper1, David Capper2, Martin Sill1, Ivo Buchhalter1, Paul A. Northcott1, Irina Leis2, Marina Ryzhova, Christian Koelsche1, Christian Koelsche2, Elke Pfaff2, Elke Pfaff1, Sariah Allen3, Gnanaprakash Balasubramanian1, Barbara C. Worst1, Barbara C. Worst2, Kristian W. Pajtler1, Sebastian Brabetz1, Pascal Johann2, Pascal Johann1, Felix Sahm2, Felix Sahm1, Jüri Reimand4, Jüri Reimand5, Alan Mackay6, Diana Carvalho6, Marc Remke4, Joanna J. Phillips7, Arie Perry7, Cynthia Cowdrey7, Rachid Drissi8, Maryam Fouladi8, Felice Giangaspero9, Maria Łastowska10, Wiesława Grajkowska10, Wolfram Scheurlen11, Torsten Pietsch12, Christian Hagel13, Johannes Gojo14, Daniela Lötsch14, Walter Berger14, Irene Slavc14, Christine Haberler14, Anne Jouvet15, Stefan Holm16, Silvia Hofer, Marco Prinz17, Catherine Keohane18, Iris Fried19, Christian Mawrin20, David Scheie21, Bret C. Mobley22, Matthew Schniederjan, Mariarita Santi23, Anna Maria Buccoliero11, Sonika Dahiya24, Christof M. Kramm25, André O. von Bueren25, Katja von Hoff13, Stefan Rutkowski13, Christel Herold-Mende2, Michael C. Frühwald26, Till Milde2, Till Milde1, Martin Hasselblatt27, Pieter Wesseling28, Pieter Wesseling29, Jochen Rößler30, Ulrich Schüller31, Martin Ebinger, Jens Schittenhelm32, Stephan Frank33, Rainer Grobholz, Istvan Vajtai, Volkmar Hans, Reinhard Schneppenheim13, Karel Zitterbart34, V. Peter Collins35, Eleonora Aronica36, Pascale Varlet, Stéphanie Puget37, Christelle Dufour38, Jacques Grill38, Dominique Figarella-Branger39, Marietta Wolter40, Martin U. Schuhmann32, Tarek Shalaby11, Michael A. Grotzer11, Timothy E. Van Meter41, Camelia M. Monoranu42, Jörg Felsberg40, Guido Reifenberger40, Matija Snuderl43, Lynn Ann Forrester43, Jan Koster36, Rogier Versteeg36, Richard Volckmann36, Peter van Sluis36, Stephan Wolf1, Tom Mikkelsen44, Amar Gajjar3, Kenneth Aldape45, Andrew S. Moore46, Michael D. Taylor4, Chris Jones6, Nada Jabado47, Matthias A. Karajannis43, Roland Eils, Matthias Schlesner1, Peter Lichter1, Andreas von Deimling1, Andreas von Deimling2, Stefan M. Pfister2, Stefan M. Pfister1, David W. Ellison3, Andrey Korshunov2, Andrey Korshunov1, Marcel Kool1 
25 Feb 2016-Cell
TL;DR: It is demonstrated that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors.

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TL;DR: A novel bioink and a dispensing technique for 3D tissue-engineering applications are presented, which incorporates a coaxial extrusion needle using a low-viscosity cell-laden bioink to produce highly defined 3D biostructures.
Abstract: A novel bioink and a dispensing technique for 3D tissue-engineering applications are presented. The technique incorporates a coaxial extrusion needle using a low-viscosity cell-laden bioink to produce highly defined 3D biostructures. The extrusion system is then coupled to a microfluidic device to control the bioink arrangement deposition, demonstrating the versatility of the bioprinting technique. This low-viscosity cell-responsive bioink promotes cell migration and alignment within each fiber organizing the encapsulated cells.

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TL;DR: HBV-related HCCs may arise on non-cirrhotic livers, further supporting the notion that HBV plays a direct role in liver transformation by triggering both common and etiology specific oncogenic pathways in addition to stimulating the host immune response and driving liver chronic necro-inflammation.

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TL;DR: It is pointed out that this assumption that very compact objects with a light ring will display a similar ringdown stage, even when their quasinormal-mode spectrum is completely different from that of a black hole, is wrong.
Abstract: It is commonly believed that the ringdown signal from a binary coalescence provides a conclusive proof for the formation of an event horizon after the merger. This expectation is based on the assumption that the ringdown waveform at intermediate times is dominated by the quasinormal modes of the final object. We point out that this assumption should be taken with great care, and that very compact objects with a light ring will display a similar ringdown stage, even when their quasinormal-mode spectrum is completely different from that of a black hole. In other words, universal ringdown waveforms indicate the presence of light rings, rather than of horizons. Only precision observations of the late-time ringdown signal, where the differences in the quasinormal-mode spectrum eventually show up, can be used to rule out exotic alternatives to black holes and to test quantum effects at the horizon scale.

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TL;DR: Several psychological factors are associated with pain secondary to neurological conditions and should be acknowledged and addressed in order to effectively treat this condition.
Abstract: Background In order to provide effective care to patients suffering from chronic pain secondary to neurological diseases, health professionals must appraise the role of the psychosocial factors in the genesis and maintenance of this condition whilst considering how emotions and cognitions influence the course of treatment. Furthermore, it is important not only to recognize the psychological reactions to pain that are common to the various conditions, but also to evaluate how these syndromes differ with regards to the psychological factors that may be involved. As an extensive evaluation of these factors is still lacking, the Italian Consensus Conference on Pain in Neurorehabilitation aimed to collate the evidence available across these topics. Objectives To determine the psychological factors which are associated with or predictive of pain secondary to neurological conditions and to assess the influence of these aspects on the outcome of neurorehabilitation. Methods Two reviews were performed. In the first, a PUBMED search of the studies assessing the association between psychological factors and pain or the predictive value of these aspects with respect to chronic pain was conducted. The included papers were then rated with regards to their methodological quality and recommendations were made accordingly. In the second study, the same methodology was used to collect the available evidence on the predictive role of psychological factors on the therapeutic response to pain treatments in the setting of neurorehabilitation. Results The first literature search identified 1170 results and the final database included 189 articles. Factors such as depression, anxiety, pain catastrophizing, coping strategies and cognitive functions were found to be associated with pain across the various conditions. However, there are differences between chronic musculoskeletal pain, migraine, neuropathy and conditions associated with complex disability with regards to the psychological aspects that are involved. The second PUBMED search yielded 252 studies, which were all evaluated. Anxiety, depression, pain catastrophizing, coping strategies and pain beliefs were found to be associated to different degrees with the outcomes of multidisciplinary programs, surgery, physical therapies and psychological interventions. Conclusions Several psychological factors are associated with pain secondary to neurological conditions and should be acknowledged and addressed.

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TL;DR: The meningioma task force of the European Association of Neuro-Oncology (EANO) assessed the scientific literature and composed a framework of the best possible evidence-based recommendations for health professionals.
Abstract: Although meningiomas are the most common intracranial tumours, the level of evidence to provide recommendations for the diagnosis and treatment of meningiomas is low compared with other tumours such as high-grade gliomas. The meningioma task force of the European Association of Neuro-Oncology (EANO) assessed the scientific literature and composed a framework of the best possible evidence-based recommendations for health professionals. The provisional diagnosis of meningioma is mainly made by MRI. Definitive diagnosis, including histological classification, grading, and molecular profiling, requires a surgical procedure to obtain tumour tissue. Therefore, in many elderly patients, observation is the best therapeutic option. If therapy is deemed necessary, the standard treatment is gross total surgical resection including the involved dura. As an alternative, radiosurgery can be done for small tumours, or fractionated radiotherapy in large or previously treated tumours. Treatment concepts combining surgery and radiosurgery or fractionated radiotherapy, which enable treatment of the complete tumour volume with low morbidity, are being developed. Pharmacotherapy for meningiomas has remained largely experimental. However, antiangiogenic drugs, peptide receptor radionuclide therapy, and targeted agents are promising candidates for future pharmacological approaches to treat refractory meningiomas across all WHO grades.

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TL;DR: In this paper, the authors provide a review of the main commercialized insulation materials (conventional, alternative and advanced) for the building sector through a holistic and multidisciplinary approach, considering thermal properties, acoustic properties, reaction to fire and water vapor resistance; environmental issues were also taken into account by means of Life Cycle Assessment approach.
Abstract: The energy consumption of a building is strongly dependent on the characteristics of its envelope. The thermal performance of external walls represents a key factor to increase the energy efficiency of the construction sector and to reduce greenhouse gases emissions. Thermal insulation is undoubtedly one of the best ways to reduce the energy consumption due to both winter heating and summer cooling. Insulation materials play an important role in this scenario since the selection of the correct material, its thickness and its position, allow to obtain good indoor thermal comfort conditions and adequate energy savings. Thermal properties are extremely important, but they are not the only ones to be considered when designing a building envelope: sound insulation, resistance to fire, water vapor permeability and impact on the environment and on human health need to be carefully assessed too. The purpose of the paper is to provide a review of the main commercialized insulation materials (conventional, alternative and advanced) for the building sector through a holistic and multidisciplinary approach, considering thermal properties, acoustic properties, reaction to fire and water vapor resistance; environmental issues were also taken into account by means of Life Cycle Assessment approach. A comparative analysis was performed, considering also unconventional insulation materials that are not yet present in the market. Finally a case study was conducted evaluating both thermal transmittance and dynamic thermal properties of one lightweight and three heavyweight walls, with different types of insulating materials and ways of installation (external, internal or cavity insulation).