Showing papers by "University of Naples Federico II published in 2016"
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
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
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
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
TL;DR: High-level consumption of plant foodstuffs consistent with an MD is associated with beneficial microbiome-related metabolomic profiles in subjects ostensibly consuming a Western diet, as well as higher urinary trimethylamine oxide levels in individuals with lower adherence to the MD.
Abstract: Objectives Habitual diet plays a major role in shaping the composition of the gut microbiota, and also determines the repertoire of microbial metabolites that can influence the host. The typical Western diet corresponds to that of an omnivore; however, the Mediterranean diet (MD), common in the Western Mediterranean culture, is to date a nutritionally recommended dietary pattern that includes high-level consumption of cereals, fruit, vegetables and legumes. To investigate the potential benefits of the MD in this cross-sectional survey, we assessed the gut microbiota and metabolome in a cohort of Italian individuals in relation to their habitual diets. Design and results We retrieved daily dietary information and assessed gut microbiota and metabolome in 153 individuals habitually following omnivore, vegetarian or vegan diets. The majority of vegan and vegetarian subjects and 30% of omnivore subjects had a high adherence to the MD. We were able to stratify individuals according to both diet type and adherence to the MD on the basis of their dietary patterns and associated microbiota. We detected significant associations between consumption of vegetable-based diets and increased levels of faecal short-chain fatty acids, Prevotella and some fibre-degrading Firmicutes, whose role in human gut warrants further research. Conversely, we detected higher urinary trimethylamine oxide levels in individuals with lower adherence to the MD. Conclusions High-level consumption of plant foodstuffs consistent with an MD is associated with beneficial microbiome-related metabolomic profiles in subjects ostensibly consuming a Western diet. Trial registration number This study was registered at clinical trials.gov as NCT02118857.
1,031 citations
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.
874 citations
Perimeter Institute for Theoretical Physics1, Niigata University2, CERN3, University of Connecticut4, Leiden University5, Korea Astronomy and Space Science Institute6, Federico Santa María Technical University7, University of California, Santa Barbara8, University of Maryland, College Park9, University of Lyon10, Claude Bernard University Lyon 111, Northwestern University12, University of Victoria13, University of Manchester14, University of Bonn15, Technische Universität München16, École Polytechnique Fédérale de Lausanne17, Stony Brook University18, Autonomous University of Madrid19, Centre national de la recherche scientifique20, University of Paris21, Moscow Institute of Physics and Technology22, Autonomous University of Barcelona23, University of Copenhagen24, Université libre de Bruxelles25, University of La Serena26, University of Valencia27, Taras Shevchenko National University of Kyiv28, Heidelberg University29, Yonsei University30, Princeton University31, Harvard University32, University of Geneva33, University of Tübingen34, Tomsk State University35, Tomsk Polytechnic University36, University of Washington37, University of Florida38, University of Hamburg39, TRIUMF40, University of Iowa41, University of Grenoble42, International Centre for Theoretical Physics43, Hokkai Gakuen University44, University of Illinois at Urbana–Champaign45, Durham University46, University of Melbourne47, University of Naples Federico II48, York University49, University of California, Berkeley50, Lawrence Berkeley National Laboratory51
TL;DR: It is demonstrated that the SHiP experiment has a unique potential to discover new physics and can directly probe a number of solutions of beyond the standard model puzzles, such as neutrino masses, baryon asymmetry of the Universe, dark matter, and inflation.
Abstract: This paper describes the physics case for a new fixed target facility at CERN SPS. The SHiP (search for hidden particles) experiment is intended to hunt for new physics in the largely unexplored domain of very weakly interacting particles with masses below the Fermi scale, inaccessible to the LHC experiments, and to study tau neutrino physics. The same proton beam setup can be used later to look for decays of tau-leptons with lepton flavour number non-conservation, $\tau \to 3\mu $ and to search for weakly-interacting sub-GeV dark matter candidates. We discuss the evidence for physics beyond the standard model and describe interactions between new particles and four different portals—scalars, vectors, fermions or axion-like particles. We discuss motivations for different models, manifesting themselves via these interactions, and how they can be probed with the SHiP experiment and present several case studies. The prospects to search for relatively light SUSY and composite particles at SHiP are also discussed. We demonstrate that the SHiP experiment has a unique potential to discover new physics and can directly probe a number of solutions of beyond the standard model puzzles, such as neutrino masses, baryon asymmetry of the Universe, dark matter, and inflation.
842 citations
TL;DR: In child/adolescent Rome IV the era of diagnosing a FGID only when organic disease has been excluded is waning, as evidence to support symptom-based diagnosis is waning and the dictum that there was no evidence for organic disease in all definitions is removed.
762 citations
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.
742 citations
Aix-Marseille University1, University of Oklahoma2, University of Iowa3, Azerbaijan National Academy of Sciences4, Université Paris-Saclay5, University of Amsterdam6, University of California, Santa Cruz7, University of Sussex8, Tel Aviv University9, Technion – Israel Institute of Technology10, University of Oregon11, Stockholm University12, King's College London13, International Centre for Theoretical Physics14, AGH University of Science and Technology15, Brookhaven National Laboratory16, Northern Illinois University17, Ludwig Maximilian University of Munich18, Rutherford Appleton Laboratory19, University of Liverpool20, University of Belgrade21, University of Göttingen22, University of Granada23, Boston University24, Joint Institute for Nuclear Research25, University of Rome Tor Vergata26, Lund University27, University of Bologna28, University of Victoria29, University of Grenoble30, National University of La Plata31, CERN32, National Technical University of Athens33, University of Salento34, University of Chicago35, Columbia University36, University of Birmingham37, University of Naples Federico II38, University of Copenhagen39, University of Washington40, University of Valencia41, Lawrence Berkeley National Laboratory42, Federal University of Rio de Janeiro43, Brandeis University44, University of Michigan45, University of Coimbra46, University of Lisbon47, University of Sheffield48, University of Geneva49, University of Texas at Austin50, Heidelberg University51, University of Milan52, National and Kapodistrian University of Athens53, Dresden University of Technology54, Novosibirsk State University55, IFAE56
TL;DR: In this article, a combined ATLAS and CMS measurements of the Higgs boson production and decay rates, as well as constraints on its couplings to vector bosons and fermions, are presented.
Abstract: Combined ATLAS and CMS measurements of the Higgs boson production and decay rates, as well as constraints on its couplings to vector bosons and fermions, are presented. The combination is based on the analysis of five production processes, namely gluon fusion, vector boson fusion, and associated production with a $W$ or a $Z$ boson or a pair of top quarks, and of the six decay modes $H \to ZZ, WW$, $\gamma\gamma, \tau\tau, bb$, and $\mu\mu$. All results are reported assuming a value of 125.09 GeV for the Higgs boson mass, the result of the combined measurement by the ATLAS and CMS experiments. The analysis uses the CERN LHC proton--proton collision data recorded by the ATLAS and CMS experiments in 2011 and 2012, corresponding to integrated luminosities per experiment of approximately 5 fb$^{-1}$ at $\sqrt{s}=7$ TeV and 20 fb$^{-1}$ at $\sqrt{s} = 8$ TeV. The Higgs boson production and decay rates measured by the two experiments are combined within the context of three generic parameterisations: two based on cross sections and branching fractions, and one on ratios of coupling modifiers. Several interpretations of the measurements with more model-dependent parameterisations are also given. The combined signal yield relative to the Standard Model prediction is measured to be 1.09 $\pm$ 0.11. The combined measurements lead to observed significances for the vector boson fusion production process and for the $H \to \tau\tau$ decay of $5.4$ and $5.5$ standard deviations, respectively. The data are consistent with the Standard Model predictions for all parameterisations considered.
618 citations
Forschungszentrum Jülich1, University of California, Davis2, Université catholique de Louvain3, ETH Zurich4, University of Southampton5, University of Texas at Austin6, University of Bonn7, James Hutton Institute8, University of California, Irvine9, Université Paris-Saclay10, Desert Research Institute11, Ghent University12, Washington State University13, Katholieke Universiteit Leuven14, University of Aberdeen15, Institut national de la recherche agronomique16, Polish Academy of Sciences17, University of Vienna18, University of Sydney19, University of Stuttgart20, Agricultural Research Service21, University of Naples Federico II22, University of California, Riverside23, Netherlands Environmental Assessment Agency24, Monash University25, University of Tübingen26, University of New England (Australia)27
TL;DR: Key challenges in modeling soil processes are identified, including the systematic incorporation of heterogeneity and uncertainty, the integration of data and models, and strategies for effective integration of knowledge on physical, chemical, and biological soil processes.
Abstract: The remarkable complexity of soil and its importance to a wide range of ecosystem services presents major challenges to the modeling of soil processes. Although major progress in soil models has occurred in the last decades, models of soil processes remain disjointed between disciplines or ecosystem services, with considerable uncertainty remaining in the quality of predictions and several challenges that remain yet to be addressed. First, there is a need to improve exchange of knowledge and experience among the different disciplines in soil science and to reach out to other Earth science communities. Second, the community needs to develop a new generation of soil models based on a systemic approach comprising relevant physical, chemical, and biological processes to address critical knowledge gaps in our understanding of soil processes and their interactions. Overcoming these challenges will facilitate exchanges between soil modeling and climate, plant, and social science modeling communities. It will allow us to contribute to preserve and improve our assessment of ecosystem services and advance our understanding of climate-change feedback mechanisms, among others, thereby facilitating and strengthening communication among scientific disciplines and society. We review the role of modeling soil processes in quantifying key soil processes that shape ecosystem services, with a focus on provisioning and regulating services. We then identify key challenges in modeling soil processes, including the systematic incorporation of heterogeneity and uncertainty, the integration of data and models, and strategies for effective integration of knowledge on physical, chemical, and biological soil processes. We discuss how the soil modeling community could best interface with modern modeling activities in other disciplines, such as climate, ecology, and plant research, and how to weave novel observation and measurement techniques into soil models. We propose the establishment of an international soil modeling consortium to coherently advance soil modeling activities and foster communication with other Earth science disciplines. Such a consortium should promote soil modeling platforms and data repository for model development, calibration and intercomparison essential for addressing contemporary challenges.
TL;DR: Following a major upgrade, the two advanced detectors of the Laser Interferometer Gravitational-wave Observatory (LIGO) held their first observation run between September 2015 and January 2016, and observed a transient gravitational-wave signal determined to be the coalescence of two black holes.
Abstract: Following a major upgrade, the two advanced detectors of the Laser Interferometer Gravitational-wave Observatory (LIGO) held their first observation run between September 2015 and January 2016. With a strain sensitivity of $10^{-23}/\sqrt{\mathrm{Hz}}$ at 100 Hz, the product of observable volume and measurement time exceeded that of all previous runs within the first 16 days of coincident observation. On September 14th, 2015 the Advanced LIGO detectors observed a transient gravitational-wave signal determined to be the coalescence of two black holes [Phys. Rev. Lett. 116, 061102 (2016)], launching the era of gravitational-wave astronomy. The event, GW150914, was observed with a combined signal-to-noise ratio of 24 in coincidence by the two detectors. Here we present the main features of the detectors that enabled this observation. At full sensitivity, the Advanced LIGO detectors are designed to deliver another factor of three improvement in the signal-to-noise ratio for binary black hole systems similar in masses to GW150914.
TL;DR: The aim of this paper is to provide a review of incidence, mortality and survival rates for colorectal cancer as well as their geographic variations and temporal trends.
Abstract: Colorectal cancer is a major public health problem, being the third most commonly diagnosed cancer and the fourth cause of cancer death worldwide. There is wide variation over time among the different geographic areas due to variable exposure to risk factors, introduction and uptake of screening as well as access to appropriate treatment services. Indeed, a large proportion of the disparities may be attributed to socioeconomic status. Although colorectal cancer continues to be a disease of the developed world, incidence rates have been rising in developing countries. Moreover, the global burden is expected to further increase due to the growth and aging of the population and because of the adoption of westernized behaviors and lifestyle. Colorectal cancer screening has been proven to greatly reduce mortality rates that have declined in many longstanding as well as newly economically developed countries. Statistics on colorectal cancer occurrence are essential to develop targeted strategies that could alleviate the burden of the disease. The aim of this paper is to provide a review of incidence, mortality and survival rates for colorectal cancer as well as their geographic variations and temporal trends.
Pennsylvania State University1, University of Science and Technology of China2, University of Arkansas3, Durham University4, Pontifical Catholic University of Chile5, Space Science Institute6, Millennium Institute7, Goddard Space Flight Center8, University of Maryland, Baltimore County9, INAF10, Nanjing University11, Space Telescope Science Institute12, European Southern Observatory13, University of Naples Federico II14, Agenzia Spaziale Italiana15, Lund University16, University of Ferrara17, University of North Texas18
TL;DR: In this article, the authors used wavdetect for initial source detection and ACIS Extract for photometric extraction and significance assessment, and created a main source catalog containing 1008 sources that are detected in up to three X-ray bands: 0.5-7.0 keV, 0.4 ×10-18, and 2.7 × 10-17 erg cm-2 s-1, respectively.
Abstract: We present X-ray source catalogs for the ≈7 Ms exposure of the Chandra Deep Field-South (CDF-S), which covers a total area of 484.2 arcmin2. Utilizing wavdetect for initial source detection and ACIS Extract for photometric extraction and significance assessment, we create a main source catalog containing 1008 sources that are detected in up to three X-ray bands: 0.5-7.0 keV, 0.5-2.0 keV, and 2-7 keV. A supplementary source catalog is also provided, including 47 lower-significance sources that have bright (Ks ≤ 23) near-infrared counterparts. We identify multiwavelength counterparts for 992 (98.4%) of the main-catalog sources, and we collect redshifts for 986 of these sources, including 653 spectroscopic redshifts and 333 photometric redshifts. Based on the X-ray and multiwavelength properties, we identify 711 active galactic nuclei (AGNs) from the main-catalog sources. Compared to the previous ≈4 Ms CDF-S catalogs, 291 of the main-catalog sources are new detections. We have achieved unprecedented X-ray sensitivity with average flux limits over the central ≈1 arcmin2 region of ≈1.9 ×10-17, 6.4 ×10-18, and 2.7 ×10-17 erg cm-2 s-1 in the three X-ray bands, respectively. We provide cumulative number-count measurements observing, for the first time, that normal galaxies start to dominate the X-ray source population at the faintest 0.5-2.0 keV flux levels. The highest X-ray source density reaches ≈50,500 deg-2, and 47% ± 4% of these sources are AGNs (≈23,900 deg-2). (Less)
University of Hamburg1, University of Valencia2, University of Bologna3, University of Udine4, Sheba Medical Center5, University of Naples Federico II6, University of Salerno7, University of Tübingen8, Autonomous University of Madrid9, Casa Sollievo della Sofferenza10, University of Freiburg11, Autonomous University of Barcelona12, University of Brescia13, University of Pisa14, University of Modena and Reggio Emilia15, University of Helsinki16
TL;DR: The inclusion of antihuman T-lymphocyte immune globulin (ATG) in a myeloablative conditioning regimen for patients with acute leukemia resulted in a significant reduction in chronic GVHD 2 years after allogeneic peripheral-blood stem-cell transplantation from an HLA-identical sibling.
Abstract: BackgroundChronic graft-versus-host disease (GVHD) is the leading cause of later illness and death after allogeneic hematopoietic stem-cell transplantation. We hypothesized that the inclusion of antihuman T-lymphocyte immune globulin (ATG) in a myeloablative conditioning regimen for patients with acute leukemia would result in a significant reduction in chronic GVHD 2 years after allogeneic peripheral-blood stem-cell transplantation from an HLA-identical sibling. MethodsWe conducted a prospective, multicenter, open-label, randomized phase 3 study of ATG as part of a conditioning regimen. A total of 168 patients were enrolled at 27 centers. Patients were randomly assigned in a 1:1 ratio to receive ATG or not receive ATG, with stratification according to center and risk of disease. ResultsAfter a median follow-up of 24 months, the cumulative incidence of chronic GVHD was 32.2% (95% confidence interval [CI], 22.1 to 46.7) in the ATG group and 68.7% (95% CI, 58.4 to 80.7) in the non-ATG group (P<0.001). The r...
TL;DR: It is shown that BCG induction of trained immunity in monocytes is accompanied by a strong increase in glycolysis and, to a lesser extent, glutamine metabolism, both in an in-vitro model and after vaccination of mice and humans.
TL;DR: In this paper, the results of a matched-filter search using relativistic models of compact-object binaries that recovered GW150914 as the most significant event during the coincident observations between the two LIGO detectors were reported.
Abstract: On September 14, 2015, at 09∶50:45 UTC the two detectors of the Laser Interferometer Gravitational-Wave Observatory (LIGO) simultaneously observed the binary black hole merger GW150914. We report the results of a matched-filter search using relativistic models of compact-object binaries that recovered GW150914 as the most significant event during the coincident observations between the two LIGO detectors from September 12 to October 20, 2015 GW150914 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 203000 years, equivalent to a significance greater than 5.1 σ.
TL;DR: A critical evaluation of the clinical data regarding the adverse effects has shown that herbal remedies are generally better tolerated than synthetic medications, Nevertheless, potentially serious adverse events, including herb–drug interactions, have been described and the need to be vigilant when using herbal remedies, particularly in specific conditions, such as during pregnancy and in the paediatric population.
Abstract: Systematic reviews and meta-analyses represent the uppermost ladders in the hierarchy of evidence. Systematic reviews/meta-analyses suggest preliminary or satisfactory clinical evidence for agnus castus (Vitex agnus castus) for premenstrual complaints, flaxseed (Linum usitatissimum) for hypertension, feverfew (Tanacetum partenium) for migraine prevention, ginger (Zingiber officinalis) for pregnancy-induced nausea, ginseng (Panax ginseng) for improving fasting glucose levels as well as phytoestrogens and St John's wort (Hypericum perforatum) for the relief of some symptoms in menopause. However, firm conclusions of efficacy cannot be generally drawn. On the other hand, inconclusive evidence of efficacy or contradictory results have been reported for Aloe vera in the treatment of psoriasis, cranberry (Vaccinium macrocarpon) in cystitis prevention, ginkgo (Ginkgo biloba) for tinnitus and intermittent claudication, echinacea (Echinacea spp.) for the prevention of common cold and pomegranate (Punica granatum) for the prevention/treatment of cardiovascular diseases. A critical evaluation of the clinical data regarding the adverse effects has shown that herbal remedies are generally better tolerated than synthetic medications. Nevertheless, potentially serious adverse events, including herb-drug interactions, have been described. This suggests the need to be vigilant when using herbal remedies, particularly in specific conditions, such as during pregnancy and in the paediatric population. Copyright © 2016 John Wiley & Sons, Ltd.
TL;DR: In this paper, an independent b-tagging algorithm based on the reconstruction of muons inside jets as well as the b tagging algorithm used in the online trigger are also presented.
Abstract: The identification of jets containing b hadrons is important for the physics programme of the ATLAS experiment at the Large Hadron Collider. Several algorithms to identify jets containing b hadrons are described, ranging from those based on the reconstruction of an inclusive secondary vertex or the presence of tracks with large impact parameters to combined tagging algorithms making use of multi-variate discriminants. An independent b-tagging algorithm based on the reconstruction of muons inside jets as well as the b-tagging algorithm used in the online trigger are also presented. The b-jet tagging efficiency, the c-jet tagging efficiency and the mistag rate for light flavour jets in data have been measured with a number of complementary methods. The calibration results are presented as scale factors defined as the ratio of the efficiency (or mistag rate) in data to that in simulation. In the case of b jets, where more than one calibration method exists, the results from the various analyses have been combined taking into account the statistical correlation as well as the correlation of the sources of systematic uncertainty.
TL;DR: To the knowledge, AAV2-hRPE65v2 is the first successful gene therapy administered to the contralateral eye and the results highlight the use of several outcome measures and help to delineate the variables that contribute to maximal benefit from gene augmentation therapy in this disease.
TL;DR: The data suggest that EHCF+LGG promotes tolerance in infants with CMA, in part, by influencing the strain-level bacterial community structure of the infant gut.
Abstract: Dietary intervention with extensively hydrolyzed casein formula supplemented with Lactobacillus rhamnosus GG (EHCF+LGG) accelerates tolerance acquisition in infants with cow's milk allergy (CMA). We examined whether this effect is attributable, at least in part, to an influence on the gut microbiota. Fecal samples from healthy controls (n=20) and from CMA infants (n=19) before and after treatment with EHCF with (n=12) and without (n=7) supplementation with LGG were compared by 16S rRNA-based operational taxonomic unit clustering and oligotyping. Differential feature selection and generalized linear model fitting revealed that the CMA infants have a diverse gut microbial community structure dominated by Lachnospiraceae (20.5±9.7%) and Ruminococcaceae (16.2±9.1%). Blautia, Roseburia and Coprococcus were significantly enriched following treatment with EHCF and LGG, but only one genus, Oscillospira, was significantly different between infants that became tolerant and those that remained allergic. However, most tolerant infants showed a significant increase in fecal butyrate levels, and those taxa that were significantly enriched in these samples, Blautia and Roseburia, exhibited specific strain-level demarcations between tolerant and allergic infants. Our data suggest that EHCF+LGG promotes tolerance in infants with CMA, in part, by influencing the strain-level bacterial community structure of the infant gut.
TL;DR: Cushing's syndrome is a serious endocrine disease caused by chronic, autonomous, and excessive secretion of cortisol, which is associated with increased mortality and impaired quality of life because of the occurrence of comorbidities as discussed by the authors.
TL;DR: It is concluded that the stochastic gravitational-wave background from binary black holes, created from the incoherent superposition of all the merging binaries in the Universe, is potentially measurable by the Advanced LIGO and Advanced Virgo detectors operating at their projected final sensitivity.
Abstract: The LIGO detection of the gravitational wave transient GW150914, from the inspiral and merger of two black holes with masses $\gtrsim 30\, \text{M}_\odot$, suggests a population of binary black holes with relatively high mass. This observation implies that the stochastic gravitational-wave background from binary black holes, created from the incoherent superposition of all the merging binaries in the Universe, could be higher than previously expected. Using the properties of GW150914, we estimate the energy density of such a background from binary black holes. In the most sensitive part of the Advanced LIGO/Virgo band for stochastic backgrounds (near 25 Hz), we predict $\Omega_\text{GW}(f=25 Hz) = 1.1_{-0.9}^{+2.7} \times 10^{-9}$ with 90\% confidence. This prediction is robustly demonstrated for a variety of formation scenarios with different parameters. The differences between models are small compared to the statistical uncertainty arising from the currently poorly constrained local coalescence rate. We conclude that this background is potentially measurable by the Advanced LIGO/Virgo detectors operating at their projected final sensitivity.
TL;DR: Clinical relevant criteria that can help to guide the physician in the management of patients with impaired or poor ovarian response are proposed, including a more specific new definition of ‘‘low prognosis’’ patients.
TL;DR: The transient noise backgrounds used to determine the significance of the event (designated GW150914) are described and the results of investigations into potential correlated or uncorrelated sources of transient noise in the detectors around the time of theevent are presented.
Abstract: On 14 September 2015, a gravitational wave signal from a coalescing black hole binary system was observed by the Advanced LIGO detectors. This paper describes the transient noise backgrounds used to determine the significance of the event (designated GW150914) and presents the results of investigations into potential correlated or uncorrelated sources of transient noise in the detectors around the time of the event. The detectors were operating nominally at the time of GW150914. We have ruled out environmental influences and non-Gaussian instrument noise at either LIGO detector as the cause of the observed gravitational wave signal.
TL;DR: The chimpanzee adenovirus 3 (ChAd3) vaccine boosted with MVA elicited B-cell and T-cell immune responses to ZEBOV that were superior to those induced by the ChAd3 vaccine alone.
Abstract: Background The West African outbreak of Ebola virus disease has caused more than 8500 deaths. A vaccine could contribute to outbreak control in the region. We assessed a monovalent formulation of a chimpanzee adenovirus 3 (ChAd3)-vectored vaccine encoding the surface glycoprotein of Zaire ebolavirus (EBOV), matched to the outbreak strain. Methods After expedited regulatory and ethics approvals, 60 healthy adult volunteers in Oxford, United Kingdom, received a single dose of the ChAd3 vaccine at one of three dose levels: 1×10(10) viral particles, 2.5×10(10) viral particles, and 5×10(10) viral particles (with 20 participants per group). Safety was assessed over the next 4 weeks. Antibodies were measured on enzyme-linked immunosorbent assay (ELISA) and T-cell responses on enzyme-linked immunospot (ELISpot) and flow-cytometry assays. Results No safety concerns were identified at any of the dose levels studied. Fever developed in 2 of the 59 participants who were evaluated. Prolonged activated partial-thromboplastin times and transient hyperbilirubinemia were observed in 4 and 8 participants, respectively. Geometric mean antibody responses on ELISA were highest (469 units; range, 58 to 4051; 68% response rate) at 4 weeks in the high-dose group, which had a 100% response rate for T cells on ELISpot, peaking at day 14 (median, 693 spot-forming cells per million peripheral-blood mononuclear cells). Flow cytometry revealed more CD4+ than CD8+ T-cell responses. At the vaccine doses tested, both antibody and T-cell responses were detected but at levels lower than those induced in macaques protected by the same vaccine. Conclusions The ChAd3 monovalent vaccine against EBOV was immunogenic at the doses tested. (Funded by the Wellcome Trust and others; ClinicalTrials.gov number, NCT02240875 .).
University of Cambridge1, Basque Government2, University of Paris-Sud3, French Institute of Health and Medical Research4, Lund University5, Umeå University6, University of Oxford7, University of Murcia8, Aalborg University9, Prevention Institute10, University of Naples Federico II11, Imperial College London12, International Agency for Research on Cancer13, University of Granada14, Utrecht University15, University of Glasgow16
TL;DR: Exposure to LDL-C-lowering genetic variants in or near NPC1L1 and other genes was associated with a higher risk of type 2 diabetes and coronary artery disease, according to a meta-analysis of genetic association studies.
Abstract: IMPORTANCE Low-density lipoprotein cholesterol (LDL-C)-lowering alleles in or near NPC1L1 or HMGCR, encoding the respective molecular targets of ezetimibe and statins, have previously been used as proxies to study the efficacy of these lipid-lowering drugs. Alleles near HMGCR are associated with a higher risk of type 2 diabetes, similar to the increased incidence of new-onset diabetes associated with statin treatment in randomized clinical trials. It is unknown whether alleles near NPC1L1 are associated with the risk of type 2 diabetes. OBJECTIVE To investigate whether LDL-C-lowering alleles in or near NPC1L1 and other genes encoding current or prospective molecular targets of lipid-lowering therapy (ie, HMGCR, PCSK9, ABCG5/G8, LDLR) are associated with the risk of type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS The associations with type 2 diabetes and coronary artery disease of LDL-C-lowering genetic variants were investigated in meta-analyses of genetic association studies. Meta-analyses included 50 775 individuals with type 2 diabetes and 270 269 controls and 60 801 individuals with coronary artery disease and 123 504 controls. Data collection took place in Europe and the United States between 1991 and 2016. EXPOSURES Low-density lipoprotein cholesterol-lowering alleles in or near NPC1L1, HMGCR, PCSK9, ABCG5/G8, and LDLR. MAIN OUTCOMES AND MEASURES Odds ratios (ORs) for type 2 diabetes and coronary artery disease. RESULTS Low-density lipoprotein cholesterol-lowering genetic variants at NPC1L1 were inversely associated with coronary artery disease (OR for a genetically predicted 1-mmol/L [38.7-mg/dL] reduction in LDL-C of 0.61 [95%CI, 0.42-0.88]; P = .008) and directly associated with type 2 diabetes (OR for a genetically predicted 1-mmol/L reduction in LDL-C of 2.42 [95%CI, 1.70-3.43]; P .001). For PCSK9 genetic variants, the OR for type 2 diabetes per 1-mmol/L genetically predicted reduction in LDL-C was 1.19 (95%CI, 1.02-1.38; P = .03). For a given reduction in LDL-C, genetic variants were associated with a similar reduction in coronary artery disease risk (I2 = 0%for heterogeneity in genetic associations; P = .93). However, associations with type 2 diabetes were heterogeneous (I2 = 77.2%; P = .002), indicating gene-specific associations with metabolic risk of LDL-C-lowering alleles. CONCLUSIONS AND RELEVANCE In thismeta-analysis, exposure to LDL-C-lowering genetic variants in or near NPC1L1 and other geneswas associated with a higher risk of type 2 diabetes. These data provide insights into potential adverse effects of LDL-C-lowering therapy.
TL;DR: In this article, the sky localization of the first observed compact binary merger is presented, where the authors describe the low-latency analysis of the LIGO data and present a sky localization map.
Abstract: A gravitational-wave (GW) transient was identified in data recorded by the Advanced Laser Interferometer Gravitational-wave Observatory (LIGO) detectors on 2015 September 14. The event, initially designated G184098 and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimates of the time, significance, and sky location of the event were shared with 63 teams of observers covering radio, optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter we describe the low-latency analysis of the GW data and present the sky localization of the first observed compact binary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-ray Coordinates Network circulars, giving an overview of the participating facilities, the GW sky localization coverage, the timeline, and depth of the observations. As this event turned out to be a binary black hole merger, there is little expectation of a detectable electromagnetic (EM) signature. Nevertheless, this first broadband campaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broad capabilities of the transient astronomy community and the observing strategies that have been developed to pursue neutron star binary merger events. Detailed investigations of the EM data and results of the EM follow-up campaign are being disseminated in papers by the individual teams.
TL;DR: These nanoparticle-matrix materials are of great interest for metals and metalloids removal thanks to the functional groups of the polymeric matrixes that provide specific bindings to target pollutants.
United States Department of Health and Human Services1, University of Göttingen2, Ludwig Maximilian University of Munich3, University of Bonn4, Charité5, Dokkyo Medical University6, University of Barcelona7, Karolinska University Hospital8, State University of Campinas9, Medical University of Graz10, University of California, San Diego11, Mayo Clinic12, Paris Diderot University13, McGill University Health Centre14, University of Queensland15, National Taiwan University16, University Hospital of Basel17, University of Adelaide18, Newcastle University19, Douglas Mental Health University Institute20, Poznan University of Medical Sciences21, Geneva College22, French Institute of Health and Medical Research23, University of New South Wales24, Neuroscience Research Australia25, Dalhousie University26, Johns Hopkins University27, Osaka University28, University of Lorraine29, Goethe University Frankfurt30, Hokkaido University31, University of Gothenburg32, Karolinska Institutet33, Veterans Health Administration34, University of Antioquia35, University of Calgary36, University of Cagliari37, Aarhus University38, University of Cincinnati39, University of Naples Federico II40, University of Salerno41, Nagoya University42, Harvard University43, Dresden University of Technology44, Montreal Neurological Institute and Hospital45, United States Department of Veterans Affairs46, National Institutes of Health47, University of Iowa48, Roy J. and Lucille A. Carver College of Medicine49, Heidelberg University50, University of Toronto51, RIKEN Brain Science Institute52
TL;DR: A genome-wide association study of lithium response in 2,563 patients collected by 22 participating sites from the International Consortium on Lithium Genetics (ConLiGen); the largest attempted so far finds a single locus of four linked SNPs on chromosome 21 met genome- wide significance criteria for association with lithium response.